Relatório Anual 2011

Transcrição

Relatório Anual
2011
ÍNDICE
1 Nota Introdutória 2. Champalimaud Centre for the Unknown
2.1. Organização
2.2. Infra-estruturas
3
9
2.2.1. Sistema de Gestão do Edifício (BMS)
2.2.2. Economia energética
2.2.3. Iluminação
2.2.4. Comunicações
2.2.5. Centro de Cálculo
2.3. Licenciamentos
2.4. Sistemas Informáticos
2.5. Restauração
2.6. Gestão dos Espaços
2.7. Manutenção e Engenharia
3. Centro Clínico Champalimaud
3.1. Organização
3.2. Actividade Clínica
3.3. Atendimento ao Doente
3.4. Acordos
16
4. Programa Champalimaud de Neurociências
22
5. Programa de Cancro
78
5.1. Programa Doutoral para Médicos
5.2. Simpósios e Reuniões
5.3. Champalimaud Metastasis Programmes
6. Prémio António Champalimaud de Visão
6.1. Reunião do Júri e selecção dos premiados
6.2. Cerimónia de atribuição do Prémio
6.3. Preparação do Prémio 2012
6.4. Conferência sobre o Prémio António Champalimaud de Visão na ARVO
7. Rede C-TRACER
7.1. C-TRACER – Índia
7.2. The Fourth Annual Champalimaud Research Symposium - LVPEI
7.3. C-TRACER – Coimbra
7.4. C- TRACER – Brasil
8. Outras Parcerias
99
8.1. Health Cluster Portugal
8.2. EARMA – European Association of Research Managers and Administrators 8.3. Centro Português de Fundações e European Foundation Centre 107
113
9. Programa Champimóvel
9.1. Eventos
9.2. Roteiro
9.3. Sessões e visitas
9.4. Reuniões
9.5. Divulgação
10. Reuniões da Fundação
121
10.1 Conselho de Curadores
11. Comunicação e Relações Públicas
11.1. Visitas ao Centro
11.2. Nos média
11.3. Livro “O binómio de Newton & a Vénus de Milo”
117
12. Biografias
124
129
Médicos Contratados em 2011
Zvi Fuks
Carlo Greco
António Parreira
Investigadores contrados em 2011 - Programa Champalimaud de Neurociências
Christian Machens
Alfonso Renart
Leopoldo Petreanu
Maria Luísa Vasconcelos
13. Gestão do Património Financeiro
Foto da capa e separadores
Rosa Reis ©
136
Leonor Beleza
Presidente da Fundação Champalimaud
Nota introdutória
O ano de 2011 ficará na nossa memória colectiva (refiro-
dãos que servimos – nós também – tornaram particula-
-me à dos que trabalhamos na Fundação Champalimaud)
rmente exigente todo o processo de montagem dos mais
como o tempo em que passámos a ocupar o maravilhoso
variados sistemas, ora virados para dentro, para a activi-
complexo à beira-Tejo a que chamamos “Champalimaud
dade exercida nas nossas instalações, ora para fora, para
Centre for the Unknown”.
permitir a circulação nos nossos espaços e a proximidade com o que fazemos das pessoas que o desejem.
Um tempo diferente, em que ficava para trás o processo
de construção física do nosso campus, e em que final-
Mas é claro que o que conta verdadeiramente na nossa
mente se consumava a execução do nosso principal
actividade é a qualidade da ciência e dos tratamentos
objectivo: um centro de investigação translacional, na
que prestamos.
área das ciências da vida, que ombreie com os melhores
do mundo e nos permita participar no combate científico
E por isso o coração do que fizemos em 2011 reside no
à doença e ao sofrimento humano.
que fizeram os nossos cientistas e os nossos médicos,
nos programas que pudemos montar, na coerência e
As instalações físicas, os licenciamentos necessários, a
na consistência do conjunto de toda a actividade, como
montagem e verificação de todos os sistemas ocupa-
sempre a concebemos.
ram, como dá conta este relatório, muita da actividade
que a Fundação desenvolveu em 2011, por forma a
O programa de neurociências existe desde 2007.
garantir o entorno eficaz e seguro do desenvolvimento
Esteve alojado, entre essa data e 2011, no Instituto
da nossa missão principal. Orgulhamo-nos, também a
Gulbenkian de Ciência, ao abrigo de um protocolo com
esse nível, do que já alcançámos. A envergadura física
a Fundação Calouste Gulbenkian, que incluía o desig-
do espaço que ocupamos, o lugar em que nos situa-
nado Champalimaud Neuroscience Program (CNP),
mos, a relação que queremos consolidar com os cida-
encontros e seminários e um doutoramento de respon-
4/5
sabilidade conjunta das duas fundações, que se mantém
de investigação clínica, garantiram a presença dos
aliás nesses termos. Ao longo do ano de 2011, decorreu
elementos essenciais para que o sector do cancro
quase todo o processo de transferência de instalações,
fosse assumido na Fundação como um projecto de
bem como um crescimento do programa, em que alguns
natureza translacional com uma forte componente
dos investigadores principais e respectivos laboratórios se
de investigação clínica e tecnológica. Já anterior-
instalaram directamente no novo campus.
mente, a entrada da Dra. Fátima Cardoso, dirigindo
a unidade da mama e, mais tarde, a do Prof. Durval
Quero nesta circunstância e neste lugar agradecer à
Costa, responsável pelo serviço de medicina nuclear,
Fundação Gulbenkian, muito em particular ao director
do Dr. Carlos Carvalho, dirigindo o departamento
do IGC, Prof. António Coutinho, o acolhimento de que
de oncologia médica, do Dr. Luís Rosa, responsável
fomos alvo, que nos permitiu em condições únicas a
pelo serviço de radiologia, e dos Prof. Jorge Cruz e
“incubação” do programa de neurociências antes de
Dr. Jorge Fonseca, responsáveis respectivamente
este poder dispor de instalações próprias.
pelas unidades de cirurgia torácica e urologia,
compuseram no conjunto uma equipa, a ser comple-
Do desenvolvimento do programa dá conta, de forma
tada este ano, que garante um altíssimo nível de
circunstanciada, este relatório. A passagem para as
prestação de cuidados e a capacidade de desen-
instalações que agora ocupam constituiu um processo
volvimento de investigação de ponta, quer na área
relativamente complexo, que não implicou apenas a
farmacológica, quer na de diagnóstico e tratamento
deslocação de pessoas e equipamentos, mas também
de alta tecnologia.
a garantia de que os trabalhos em curso podiam ser
prosseguidos nas novas instalações e a reorganização
O Dr. Zvi Fuks, antigo director de radioterapia do
de todo o sistema de plataformas e de pessoal de apoio.
Memorial Sloan Kettering Cancer Center, em Nova
Ainda em 2011, o CNP organizou o simpósio inaugural
Iorque, reputado especialista e cientista a nível mundial,
nas novas instalações, bem como uma série de iniciativas
creditado como autor de alguns dos maiores avanços
destinadas ao grande público (Ar), num caso e noutro
no domínio do tratamento do cancro, e recebido no
com ampla participação, do mundo científico e de pes-
ano de 2011 como membro do Instituto de Medicina da
soas interessadas sem formação especial, revelando uma
Academia Nacional de Ciências dos EUA, dirige agora
grande capacidade de alcance na área especializada e
todo o conjunto do Centro, garantindo a coerência do
na divulgação da ciência.
projecto e a excelência da investigação e da prestação
de cuidados. Tem sido capaz de captar, para trabalhar
No conjunto de financiamentos e distinções obtidas em
no Centro ou com ele colaborar, um conjunto de
2011 pelos neurocientistas, quero distinguir, pela sua
técnicos de alta capacidade e de instituições com
relevância, que Megan Carey e Rui Costa obtiveram
quem precisamos de manter uma prática constante de
bolsas do prestigiadíssimo Howard Hughes Medical
colaboração e de exigência.
Institute, que os considerou como futuros líderes nas
áreas que investigam.
O esforço de recrutamento e de constituição de
equipas, que prossegue, iniciado basicamente em
Na outra grande área de trabalho do Centro, o cancro, o
2011, assenta na ideia de grupos multidisciplinares
ano que passou foi decisivo na definição do respectivo
por áreas de cancro, apoiadas em equipas transver-
programa científico e no lançamento da base de
sais de diagnóstico e terapêutica, com um interesse
prestação de cuidados clínicos que o sustenta.
científico que incide de forma especial na área da
prevenção e tratamento das metástases. Os serviços
O recrutamento e contratação do Dr. Zvi Fuks como
clínicos dedicam-se à prevenção, diagnóstico precoce
director do Centro no início do ano, imediatamente
e tratamento do cancro usando e desenvolvendo os
seguido da escolha do Prof. António Parreira como
conhecimentos mais actualizados e as tecnologias
director clínico e do Prof. Carlo Greco como director
mais sofisticadas.
Foi montado durante o ano de 2011 um sistema espe-
Control” (APOC). Atribuído em ano ímpar, destinava-se
cial e humanizado de recepção das pessoas que nos
a reconhecer uma instituição em plena actividade que
procuram, baseado na individualização do acolhimento
se tivesse distinguido no terreno, em áreas do mundo
e na manutenção da privacidade, num ambiente que
em desenvolvimento, no combate à cegueira. O APOC
preserva até ao limite do possível a normalidade dos
constitui uma parceria formada pela OMS, o Banco
lugares e dos tempos, tentando suprimir tudo o que
Mundial, governos africanos de países atingidos pela
um ambiente hospitalar clássico introduz de pressão e
chamada, em linguagem corrente, cegueira dos rios,
sofrimento acrescido.
organizações não governamentais e uma empresa
farmacêutica, a Merck, que fornece gratuitamente o
A manutenção de um nível elevado de prestação de
medicamento necessário. O objectivo é muito ambicioso:
cuidados e de excelência na ciência supõem, aí sim,
acabar com uma doença profundamente incapacitante,
uma pressão constante sobre os meios, os espaços e
que atormenta gerações de comunidades que vivem
as pessoas que trabalham no Centro. Tentamos fazê-lo
em áreas relativamente isoladas, junto aos rios. O
de forma a motivar e entusiasmar a excelente equipa de
APOC é reconhecido por ter salvo da cegueira milhões
colaboradores que temos vindo a recrutar.
de pessoas em áreas muito pobres, utilizando, não
apenas os parceiros que a compõem, mas uma sábia
A revista americana The Scientist, que produz anualmente
mobilização das comunidades e dos seus dirigentes,
rankings de instituições científicas que constituem os
para chegar onde é necessário e convencer as pessoas
melhores sítios para trabalhar em pós-doutoramento,
a deixarem-se imunizar contra a doença. De entre os
distinguindo entre as que estão nos EUA e as que estão
países africanos onde actua, assumem particular
em todo o resto do mundo, considerou que a melhor
relevância, para nós, Portugueses, a Guiné-Bissau,
dessas instituições fora de solo americano é a Fundação
Angola e Moçambique.
Champalimaud. Este destaque, que se baseia na opinião
dos próprios cientistas, enche-nos de orgulho e de
A cerimónia de atribuição do Prémio regressou à nossa
responsabilidade. Ajuda-nos na visibilidade, cá dentro e
fórmula habitual, depois de em 2010 ter sido incluída
lá fora, que obviamente procuramos. Mas também nos
na inauguração das nossas instalações. Voltou a ser o
ajuda a encontrar um estado de permanente alerta para
momento mais solene do ano da Fundação, como sempre
praticar sistematicamente os mais elevados padrões de
sob a presidência do Senhor Presidente da República,
exigência e qualidade.
pela primeira vez utilizando o magnífico anfiteatro ao
ar livre de que dispomos. Proporcionou momentos
A enorme curiosidade em torno do nosso Centro e
simultaneamente de solenidade e de passagem da
das suas instalações, bem como a nossa política de
mensagem de solidariedade que o Prémio, e esta
proximidade com os cidadãos e o nosso desejo de
edição em particular, encerra, bem como de usufruto
que saibam quem somos e o que fazemos, levam-nos
de um quadro de beleza único e de apreciação de uma
a organizar com carácter sistemático visitas de grupos e
execução musical de grande qualidade.
de pessoas, que têm ocasião de conhecer os locais e
de, moderadamente, entrar em contacto com os nossos
Prosseguiram os trabalhos de investigação translacional
colaboradores. Em 2011, estas visitas, quer de pessoas
no âmbito do C- TRACER (Champalimaud Translational
em função de posições que ocupam, em Portugal ou no
Centre for Eye Research), em Hyderabad, na Índia,
estrangeiro, quer de grupos de anónimos, revelaram-se
onde se faz investigação de ponta na melhoria dos
muito importantes no nosso relacionamento com o exterior
mecanismos da visão, e se põe em prática essa
e, com todos os cuidados que a progressiva ocupação
investigação. Já foi possível realizar transplantes de
dos edifícios sugere, prosseguem intensamente.
córnea, recorrendo à utilização de células estaminais
adultas, sem necessidade de uso de laboratório, numa
O Prémio António Champalimaud de Visão foi atribuído
simplificação sofisticada de procedimentos que permitirá,
em 2011 ao “African Programme for Onchocersiasis
como sempre ambicionámos, levar as técnicas a meios
6/7
menos dotados de complexas instalações, em países em
ao longo de um ano que não deu grande sossego aos
desenvolvimento. Iniciou a sua actividade, no âmbito do
mercados financeiros, o que nos levou, logo no início,
que chamamos C-TRACER 2, a AIBILI (Associação para a
a adoptar um perfil de investimentos mais conservador.
Investigação Biomédica e Inovação em Luz e Imagem), em
Também no seguimento do que já tive ocasião de
Coimbra, com a preparação de projectos e um simpósio
anteriormente escrever, aumentámos significativamente
científico em que também participaram representantes
a nossa capacidade de nos tornarmos menos
do LV Prasad Eye Institute, onde se situa o C-TRACER
dependentes do nosso portefólio financeiro, numa linha
original, e ainda o Prof. Rubens Belfort, reconhecido
de actuação que colherá progressivamente os seus
oftalmologista brasileiro que dirige o Instituto Paulista de
frutos. Mantemos um rigor muito grande na contratação
Estudos e Pesquisas em Oftalmologia, em São Paulo,
e na utilização de meios, resistindo a todas as pressões
que constituirá o C-TRACER 3, como logo em Coimbra
e rentabilizando num esforço constante os meios de que
foi imaginado e decidido. Alargamos assim a nossa rede
dispomos.
de instituições associadas que se dedicam à investigação da saúde visual dirigida à obtenção de resultados
Quero por fim dirigir uma palavra de profundo
na melhoria da prevenção e do tratamento de doenças.
reconhecimento a todos os que nos ajudaram, ao longo
Escusado será sublinhar o significado de associar, por
do ano de 2011, a cumprir os nossos objectivos. Aos
esta via, à Fundação Champalimaud, e entre si, instituições
membros dos órgãos da Fundação, aos membros do júri
de investigação na Índia, em Portugal e no Brasil.
do Prémio António Champalimaud de Visão, a todos os
nossos colaboradores e aos inúmeros amigos que nos
Entre nós, prosseguiu a actividade do Champimóvel,
estimulam com o seu saber e dedicação a avançar, o meu
projecto de promoção da actividade científica entre os
muito obrigada. A nossa caminhada não abranda, torna-
jovens que percorre as escolas e cada vez mais iniciativas
-se cada vez mais exigente. Dependemos de muitos, e
locais de várias naturezas, onde há aglomerações de
a todos continuaremos a recorrer no cumprimento da
pessoas interessadas, com um êxito e pedidos de
missão que nos confiou António Champalimaud.
visita em permanente crescimento. O Champimóvel
suscita o interesse que esperávamos nos jovens dos 9
aos 14 anos, para quem foi pensado, mas na verdade
entusiasma inúmeros assistentes de outras idades.
Cada vez mais um hábito estabelecido, promovemos a
edição em 2011 de um livro, desta feita uma antologia
de poesia dedicada à ciência na literatura portuguesa,
coligida e introduzida por Vasco Graça Moura e Maria
Bochicchio, intitulada O binómio de Newton e a Vénus
de Nilo, que distribuímos no Natal pela nossa rede de
amigos. Aos que não se exprimem em português,
enviámos uma antologia em língua inglesa, incluindo
a tradução de alguns poemas originariamente em
português, com o título A Quark for Mister Mark. Esta
é uma forma que temos encontrado de nos fazer
lembrados, num momento especial, por um número
crescente de pessoas que nos vão acompanhando e
ajudando no caminho que percorremos.
As contas, que agora tornamos públicas, em relação a
2011, reflectem a nossa situação patrimonial e o percurso
Champalimaud
Centre for the
Unknown
2. Champalimaud Centre for the Unknown
2.1. Organização
2.2.3. Iluminação
2.3. Licenciamentos
2.5. Restauração
Champalimaud Centre
for the Unknown
2.1. Organização
O ano de 2010 foi o ano de conclusão física do edifício
•Definição do processo de autorizações de compras;
•Definição dos circuitos logísticos e estruturas de
recepção e armazenagem.
do Centro de Investigação Champalimaud, construído no
rigoroso cumprimento do prazo, das especificações técni-
Em paralelo, foi definido o modelo de codificação para
cas e dos custos previstos. Mas tão ou mais importante
medicamentos, material clínico, bens de imobilizado,
que a realização física é o desenho rigoroso da organiza-
projectos de investigação, projectos de investimento,
ção necessária para o funcionamento e gestão das áreas
actos médicos, equipamentos em manutenção, etc.
da Clínica e da Investigação.
Já o ano de 2011 foi o ano em que começou a ser
implementada essa organização, que cobriu actividades tão diversas como:
•Estabelecimento da macroestrutura do Centro de
Investigação Champalimaud e definição dos recursos
humanos e materiais necessários ao cumprimento
dos seus objectivos;
•Definição das principais funções do Centro;
•Definição da estrutura de centros de responsabilidade;
•Definição do relacionamento funcional das diversas
estruturas;
•Definição dos circuitos da área clínica;
Centro de Investigação da Fundação Champalimaud
10/11
A resposta no caso presente é sem dúvida muito
positiva e tem vindo a ser dada não só pelos doentes
que começámos a tratar no final do ano, mas também
pelos médicos, pelos investigadores, por todos os que
trabalham no Centro e pelos inúmeros visitantes que
elogiam as nossas instalações.
De realçar que não houve, durante o primeiro ano de
arranque, quaisquer alterações à concepção inicial do
edifício (com os custos e inconvenientes que normalmente
implicam essas alterações). Efectivamente, a flexibilidade
técnica com que o edifício foi projectado e construído
tem superado todas as novas necessidades.
O edifício foi projectado com áreas de expansão para
a Clínica e Investigação que rondam 40% do espaço
actualmente ocupado por estas actividades, o que permitirá absorver futuros projectos de desenvolvimento.
O edifício tem um avançado sistema de gestão técnica,
que fornece em tempo real a situação de cerca de
6000 sensores (temperatura, pressão, humidade, etc.),
permitindo um controlo 24/24 horas de todas as infra-estruturas, emitindo alertas sobre qualquer anomalia
Jardim da Quimioterapia
para os responsáveis, de forma a permitir uma actuação
imediata sempre que se justifique.
Durante o ano de 2011 foi parametrizado este sistema, à
Durante o ano de 2011 foi iniciada a utilização da globa-
medida que foram iniciados os novos serviços da Clínica
lidade das infra-estruturas do Centro de Investigação
e da Investigação.
Champalimaud, nomeadamente das áreas de Investigação, Clínica, Auditório, Centro de Exposições, Anfiteatro
e Darwin’s Café e Cafetaria.
A economia energética foi um requisito imposto aos
Foi o verdadeiro teste à concepção funcional do
projectistas, de forma a garantir a sustentabilidade do
edifício, à solução arquitectónica, às infra-estruturas de
edifício do Centro Champalimaud dentro de exigentes
ar condicionado, energia eléctrica, redes de fluidos e
parâmetros de rentabilidade. O edifício foi certificado
sistemas de segurança, que durante cerca de três anos
energeticamente como classe A.
concebemos, projectámos e construímos.
Durante 2011 foram instalados a maior parte dos sisteA questão que normalmente se levanta quando se finaliza
mas relacionados com a economia de energia, desde
um edifício, particularmente com o grau de complexidade
os painéis solares térmicos ao controlo centralizado da
do Centro de Investigação Champalimaud, em que o
iluminação, à gestão centralizada, aos ensombramentos
número de incógnitas à partida era muito elevado, é a
e revestimentos térmicos até à toma de água no rio Tejo
seguinte: funciona?
para arrefecimento do ar.
2.2.3. Iluminação
O projecto de iluminação interior e exterior, que foi
Toda a infra-estrutura de processamento de dados
concebido com uma grande preocupação a nível
começou a ser instalada em 2011 num Centro de
estético e energético, visou também elevados níveis
Cálculo externo em cloud computing, garantindo o
de flexibilidade e conforto para todos os utentes,
fornecedor os níveis de serviço contratados de forma
nomeadamente os doentes, os investigadores e o corpo
a racionalizar os recursos humanos e técnicos da
clínico.
Fundação Champalimaud.
Foi também instalado um sistema domótico para gestão
Esta solução permite flexibilizar a utilização dos meios
da iluminação, o qual durante 2011 foi optimizado de
informáticos, nomeadamente servidores ou armazena-
acordo com as necessidades crescentes do Centro
mento de dados, permitindo adequados níveis de
Champalimaud.
segurança e tempos de resposta a novas solicitações
dos utilizadores.
Terraço da Clínica
2.3. Licenciamentos
O sistema de comunicações state-of-the-art que integra
Após o término da obra de construção do Centro
a rede de voz fixa, móvel e de dados foi concebido no
Champalimaud em 5 de Outubro de 2010, o departa-
respeito pelos mais elevados níveis de exigência, quer
mento de engenharia da Fundação iniciou os trabalhos
no que respeita à segurança, quer ao desempenho e
de comissionamento das instalações, ensaiando e
adaptabilidade às crescentes e específicas neces-
testando todos os equipamentos e sistemas montados a
sidades de comunicação do Centro Champalimaud.
fim de garantir os padrões de exigência das respectivas
entidades licenciadoras. Assim, depois de seis meses
Durante 2011 foi implementada toda a estrutura do
de testes e ensaios, iniciámos um largo processo de
sistema de comunicações, tendo vindo a crescer
inspecções por parte das entidades licenciadoras. Após
de forma faseada com o arranque de cada um dos
inspecção dos serviços da Direcção Geral de Energia,
serviços.
Regimento de Sapadores Bombeiros e Urbanismo do
Município de Lisboa, o Centro obteve o licenciamento
para utilização emitido pela Câmara Municipal a 17 de
Junho de 2011.
12/13
Cafetaria e Darwin’s Café
2.5. Restauração
Os sistemas informáticos da Fundação Champalimaud
Durante o ano de 2011 foi estabelecida uma parceria
foram desenhados de forma a responder às necessida-
com a LA Café para a exploração do Darwin’s Café e
des das suas duas principais áreas funcionais: a Clínica
da cafetaria. O Darwin’s tornou-se um dos locais mais
e a Investigação.
procurados de Lisboa, tendo servido no primeiro ano
(em 11 meses) cerca de 74 000 refeições.
Durante 2011 foi iniciada a instalação dos sistemas da
área administrativa, nomeadamente a gestão de recursos
A cafetaria serve refeições aos investigadores, aos
humanos, o recrutamento e a contabilidade geral.
colaboradores da Fundação e da Clínica, aos doentes
e respectivos acompanhantes, bem como a visitantes
Na área clínica, foi iniciada a instalação da gestão de
em geral. Durante o ano de 2011 (em sete meses) foram
doentes, processo clínico electrónico, enfermagem e
servidas cerca de 21 000 refeições, atingindo uma média
facturação a doentes.
diária de 140 refeições, mas em crescendo sistemático.
Com especial incidência na área de investigação, mas
eventos na Fundação Champalimaud.
A estrutura do Darwin’s fez ainda o catering de 84
transversal a toda a instituição, foi desenvolvido e implementado um sistema de requisições de compras que
permite optimizar e controlar a logística de aquisições.
Na área da manutenção e engenharia foi implementado
um sistema informático para garantir a manutenção
curativa, preventiva e preditiva.
Durante o ano de 2011 o departamento de Gestão dos
Espaços organizou os mais variados tipos de eventos,
desde simpósios, congressos, concertos, corporate
events, até assembleias gerais de accionistas de
algumas empresas.
Realizaram-se 90 eventos com a participação de
mais de 30 000 pessoas, utilizando o Auditório, o
Anfiteatro exterior, o Centro de Exposições e as salas
polivalentes.
Auditório
O Serviço de Manutenção e Engenharia começou a
Ainda durante o ano de 2011 foram também estabeleci-
acompanhar as obras de construção do Centro de
das as rotinas de manutenção de todos os sistemas e
Investigação Champalimaud um ano antes da sua
equipamentos, com especial enfoque nas áreas Clínica
finalização, de forma a conhecer todos os detalhes dos
e de Investigação, tendo sido criado um sistema de
seus sistemas e a sua operação, com vista à posterior
e-ticketing para resposta atempada às necessidades
condução e manutenção.
de todos os utilizadores.
Em 2011, a área de Engenharia concentrou-se essencial-
Foi também efectuada a “afinação” do edifício, nomeada-
mente na instalação e arranque dos equipamentos espe-
mente nas áreas de electricidade, ar condicionado,
cíficos das áreas Clínica e de Investigação.
iluminação, sistemas de segurança e tratamento de
fluidos.
Centro Clínico
Champalimaud
3. Centro Clínico Champalimaud
3.1. Organização
3.4. Acordos
16/17
Centro Clínico Champalimaud
Centro Clínico Champalimaud
3.1. Organização
cialistas, enfermeiros e outros – que se dedicam pre-
A organização e início de actividades do Centro Clínico
considerados prioritários no desenvolvimento do Centro
Champalimaud (CCC) verificou-se a partir de Março
Clínico e tendo em atenção os objectivos programáticos
de 2011, com base nas linhas mestras definidas pela
da Fundação. São eles o cancro da mama, o cancro do
administração da Fundação e tendo como objectivo
pulmão, o cancro digestivo e o cancro da próstata.
ferencialmente a cada um dos tipos de cancro que foram
essencial o de criar uma unidade de excelência dedicada à investigação e tratamento do cancro.
Foi também considerado importante criar uma unidade
multidisciplinar distinta, com objectivos mais abrangentes,
Foi assim definido como missão do CCC o desenvolvi-
essencialmente vocacionada para o estudo e tratamento
mento de actividades de investigação em paralelo com a
actividade clínica, recorrendo a modalidades avançadas
e tecnologicamente inovadoras, no diagnóstico e tratamento do cancro.
A organização do Centro Clínico tem como elementos
essenciais e estruturantes as Unidades Multidisciplinares de Patologia (DMT – disease management teams),
que correspondem a unidades multidisciplinares, cada
uma delas dirigida a toda a problemática de diagnóstico,
tratamento e acompanhamento de doenças neoplásicas de órgão ou sistema. Congregam assim equipas
multidisciplinares de técnicos de saúde – médicos espe-
Tomografia Axial Computorizada (TAC)
Área técnica de imagiologia
de doentes com tumores metastizados, em particular
Centro de Patologia Morfológica e Molecular ALTHIA,
com metástases no fígado, no pulmão, nos ossos e no
com sede em Barcelona, no que respeita ao diagnós-
sistema nervoso central. Considerou-se assim na fase
tico anatomopatológico.
inicial da sua actividade a organização de 5 DMTs –
Mama, Pulmão, T. Digestivos, Próstata e Metástases.
A área terapêutica inclui um espaço de Hospital de
Dia para tratamento ambulatório com modalidades de
O Centro Clínico dispõe de instalações e equipamentos
poliquimioterapia intravenosa, dispondo de 29 cadeirões
adequados à prática da oncologia moderna, com
para ciclos de quimioterapia de curta duração (2 a 3
instalações próprias para as consultas médicas e de
horas) e quatro quartos individuais, preparados para
enfermagem nas diversas áreas de patologia, com
tratamento ambulatório com quimioterapias de longa
diferenciação do espaço de consultas e exames
duração (> 4 horas).
relacionados com o diagnóstico precoce, permitindo
a separação entre os fluxos de doentes oncológicos
e indivíduos incluídos nos programas de rastreio e
diagnóstico precoce.
Dispõe também de espaços adequados para os serviços de diagnóstico e de tratamento. A área diagnóstica
inclui a radiologia convencional, ultra-sonografia, tomografia computadorizada (TC), ressonância magnética
(RM), cintigrafias (SPECT), tomografia por emissão de
positrões (PET) e espaço laboratorial para patologia
clínica convencional e patologia morfológica. Apenas
o diagnóstico de patologia clínica e de patologia
morfológica não foi ainda activado no CCC, estando
assegurado por prestação externa, pelo Hospital da
Cruz Vermelha no que respeita à patologia clínica e pelo
Acelerador Linear
18/19
O plano funcional de cada uma das DMTs pressupõe
tendo o ano terminado com 45 sessões de radioterapia
um trabalho de equipa organizado entre médicos
administradas.
especialistas com particular experiência e interesse
na respectiva área de patologia, desde o diagnóstico
A actividade cirúrgica teve início no Hospital da Cruz
à terapêutica, em articulação com outros profissionais
Vermelha, de acordo com o planeado, bem como o
de saúde que complementam a prestação de todos os
recurso a tratamentos de quimioterapia ambulatória.
cuidados médicos necessários à abordagem abran-
Até ao final de Dezembro 2011, foram realizadas 15
gente e completa de doentes com diferentes tipos de
intervenções cirúrgicas e foram tratados com quimio-
cancro (enfermagem, psico-oncologia, nutrição, apoio
terapia ambulatória 10 doentes.
social).
O Centro Clínico Champalimaud (CCC) iniciou as suas
A actividade clínica teve início no segundo semestre
actividades através da constituição de uma equipa para
de 2011, com a abertura de consultas de Oncologia
atendimento ao doente, composta por pessoas jovens,
Médica, de Cirurgia Oncológica e de Radioterapia,
desempregadas e com dinamismo para agarrar um
tendo também entrado em funcionamento o sector de
novo desafio.
diagnóstico, nomeadamente a ultra-sonografia, a TAC e
RM e a Medicina Nuclear (PET-CT e cintigrafias). Até ao
Esse desafio passou pela criação da função de gestor
final de 2011 foram atendidos cerca de 400 doentes,
de doentes (GD), com o objectivo de tornar o serviço
correspondendo a 250 consultas de Oncologia Médica
ao cliente personalizado, acessível, simpático e focado
e Radioterapia e 140 exames diagnósticos (TAC, RM e
apenas no bem-estar dos doentes e das suas famílias
Medicina Nuclear).
ou amigos.
O equipamento de radioterapia entrou em funciona-
Todos os GDs gerem uma pool de doentes, que lhes
mento com a activação de um acelerador linear, após as
é atribuída no primeiro contacto dos doentes com o
necessárias fases de verificação e testes e obtenção do
Centro, assegurando e minimizando a burocracia entre
correspondente licenciamento. O primeiro tratamento de
o Centro Clínico Champalimaud, as seguradoras ou
radioterapia externa ocorreu já em Dezembro de 2011,
subsistemas e a instituição parceira, Hospital da Cruz
Vermelha.
Aos ingredientes acima indicados, foi associada a
tecnologia exclusiva de utilização de tablet computers
para os GDs, acoplados a smartphones para os
doentes, permitindo aos mesmos conhecer a história da
instituição, os locais de lazer e de uso comum, o seu
agendamento e os eventuais atrasos, ao mesmo tempo
que se deslocam e usufruem dos espaços e jardins
da Fundação Champalimaud.
Para completar o conforto dos doentes foram ainda
disponibilizados carros de refeições com pequenos
snacks e bebidas, ao serviço de todos os que se desloquem ao Centro Clínico para realização de exames,
Utilização de tecnologia Tablet Computers e Smartphones
no atendimento aos doentes
consultas ou tratamentos, ou simplesmente para acompanhar um familiar ou amigo.
meira fase, com o maior subsistema de saúde público
(ADSE), com o maior subsistema de saúde militar
(IASFA) e com a seguradora de saúde com a maior
quota de mercado (Multicare).
Por outro lado, sendo uma instituição sem fins lucrativos
e não perspectivando a margem de lucro, apenas incorporando os custos de investigação e cuidados de saúde,
foi elaborada uma tabela de preços mais acessível para
disponibilização dos nossos serviços de saúde a quem
mais precisa.
Serviços de apoio ao doente
3.4. Acordos
Esta unidade de saúde “aberta ao povo português
e construída para o povo português” deu prioridade
à negociação de acordos com as seguradoras e
subsistemas mais relevantes.
Pretendeu-se disponibilizar o acesso ao maior número
de doentes possível assegurando acordos, numa priGabinete de consulta
Programa
Champalimaud
de Neurociências
4. Programa Champalimaud de Neurociências
22/23
Laboratório de Neurociências
Programa Champalimaud
de Neurociências
O Programa Champalimaud de Neurociências
Em Setembro realizou-se o primeiro “Champalimaud
(CNP), coordenado pelo Doutor Zachary Mainen,
Neuroscience Symposium”, com a participação
foi criado em 2007, e em 2011 transferiu-se
de neurocientistas internacionais de renome e
definitivamente para o Champalimaud Centre for
com uma assistência notável ao longo de três
the Unknown. Conta com dezasseis grupos de
dias. Pouco depois iniciaram-se as conferências
investigação, liderados por treze investigadores
mensais denominadas “AR”, que versam uma
principais (PIs) residentes, um “Research Fellow”
variedade de temas científicos e de assuntos
e dois investigadores associados externos. Tem
correlacionados e que são destinadas a uma
como grande objectivo a compreensão das funções
audiência mais genérica não exclusivamente
cerebrais através de abordagens integradas,
científica, estando abertas ao público em geral;
com recurso a técnicas avançadas de biologia
as duas primeiras conferências, sobre a “máquina
molecular, de fisiologia e de imagem em diversos
cerebral” (brain-machine) e a “criatividade”, tiveram
modelos animais. Em 2011 foram publicados três
um êxito retumbante, abrindo assim a Fundação
artigos de revisão e dez artigos originais. No final
Champalimaud e o seu Programa de Neurociências
do ano os investigadores Megan Carey e Rui Costa
a um mundo alargado num esforço permanente de
foram distinguidos com o prémio internacional
divulgação da ciência.
“Early Career Scientist” atribuído pelo Howard
Hughes Medical Institute.
O CNP organiza também desde há anos o
International Neuroscience Doctoral Programme
(INDP), com grande sucesso.
DIRECTOR
Zachary Mainen
potentiation pattern of single synapses, which was
published in Neuron (I. Israely). Also, at the end
of 2011, CNP investigators R. Costa and M. Carey
The Champalimaud Neuroscience Programme
received the International Early Career Scientist
(CNP) was created in 2007 through a collaborative
Award by Howard Hughes Medical Institute.
agreement between the Champalimaud Foundation
and the Calouste Gulbenkian Foundation. It is
The CNP also organizes the International Neuros-
a basic research team with the broad aim of
cience Doctoral Programme (INDP). In this program
understanding brain function through integrative
students are provided with a broad educational
biological approaches. CNP laboratories apply
background through both formal classes and
advanced molecular, physiological and imaging
hands-on experience in basic topics in contem-
techniques to elucidate the function of neural
porary neuroscience such as cellular and synaptic
circuits and systems in animal models that include
physiology, sensation and action and cognitive
Drosophila, mouse, rat and zebrafish.
neuroscience. Quantitative approaches are emphasized and students also receive background courses
As of December 2011 the CNP comprises sixteen
in mathematics and programming.
independent research groups, including thirteen
in-house principle investigators, one research
In 2011, CNP investigators began conducting
fellow and two associated external principle
their research at the recently inaugurated
investigators. This year, the CNP was joined by
Champalimaud Center for the Unknown (CCU).
three new investigators (C. Machens, L. Petreanu,
There, in September 2011, the first Champalimaud
A. Renart), one research fellow (A. Kampff), and
Neuroscience Symposium was held, featuring
recruited another investigator who will join the
lectures by key neuroscientists from across the
programme in 2012.
world. Soon after, the Ar monthly event-series
began. These outreach events, targeted at a
In 2011, CNP investigators published 3 review
general audience, explore different aspects of
articles and 10 refereed research articles, including
scientific and science-related topics such as brain-
a study on the role of the dendritic branch in the
machine interface and creativity.
24/25
INVESTIGATORS
mechanisms within the cerebellum have been
Megan Carey
identified and proposed as cellular substrates of
learning for this behavior. One class of molecules
Neural Circuits and Behavior
that appears to be important is endocannabinoids.
Group Members
Both cannabis users and cannabinoid receptor
Catarina Albergaria (PhD Student)
(CB1) knockout mice exhibit impairments in delay
Ana Sofia Machado (PhD Student)
eyelid conditio-ning. However, endocannabinoids
Daniel Schlacks (Research Assistant)
are important for multiple plasticity mechanisms
Claire Monroy (Technician)
at many synapses, and it is not clear exactly where
or how they act to modulate eyeblink conditioning.
We are taking a genetic approach to this problem,
Research Summary:
by deleting CB1 receptors selectively from
synaptic
identified cell types within the brain. Through
mechanisms interact within neural circuits
behavioral and electrophysiological experiments
to control behavior is a fundamental goal of
in these mice, we hope to constrain both the
neuroscience. To achieve that goal, we need a
candidate sites and mechanisms of action for
thorough understanding of behavior as well as
CB1 receptors in eyelid conditioning.
Understanding
how
cellular
and
a detailed knowledge of the underlying neural
circuit. With this in mind, we focus our research
on the cerebellum, a brain area that is critical
for coordinated motor control and motor learning
Understanding the role of the cerebellum in
gait coordination
and whose circuitry is relatively simple and well
The cerebellum is important for coordinated
understood. The cerebellar circuit is highly
motor control. Gait ataxia, which is a lack of
organized and consists of identified cell types
coordination during walking, is one of the most
with known synaptic connectivity. Many of the
prominent symptoms of cerebellar damage.
neuron types in the cerebellum are molecularly
However, the precise role of the cerebellum in
identifiable, and existing technologies allow
controlling gait is not well understood. Although
us to target transgenes to specific neuronal
sophisticated genetic tools exist to manipulate
populations. By comparing specific aspects of
the cerebellar circuit in mice, analyses of
behavior and neural activity across mice in
mouse gait have typically been limited to gross
which we have targeted genetic perturbations
performance measures and lack detail about
to different cell types, we hope to determine
precision and timing of limb movements. Here
links between cellular function, circuit activity,
we are developing high-speed video methods for
and behavior. We take a multifaceted approach,
measuring and analyzing mouse gait to identify
including quantitative analysis of cerebellum-
specific gait parameters that are cerebellum-
dependent behaviors, in vivo measurements of
dependent. We will use genetic tools, including
neural activity, and in vitro studies of synaptic
cell-type specific expression of tetanus toxin
transmission and plasticity.
and optogenetics, to manipulate activity in
individual cerebellar cell types and examine
Projects:
their contributions to gait control.
Dissecting the role of endocannabinoids in
eyeblink conditioning
Delay eyelid conditioning is a simple form of
Endocannabinoids and motor performance and
learning
classical conditioning that depends critically on an
Endocannabinoids
intact cerebellum. Multiple synaptic plasticity
lators that act through CB1 receptors to modulate
are
powerful
neuromodu-
synaptic transmission and activity throughout
the brain. While a role for endocannabinoids
in synaptic plasticity is clear, the importance of
endocannabinoid signaling for motor control and
learning is less well understood. Several studies
have shown that CB1 receptor knockout mice show
decreased locomotion and exploratory behavior,
but do not exhibit severe coordination deficits or
ataxia. This is perhaps surprising, since many
forms of endocannabinoid-dependent synaptic
plasticity have been described at various synapses
within the cerebellum and other structures known
to be important for coordinated motor control.
However, most previous studies have been limited
to open field behavior and rotarod performance
and may have missed more subtle phenotypes.
Here, we are combining sensitive assays of mouse
motor performance and learning and using a cellspecific knockout approach to elucidate the role of
endocannabinoids in motor control and learning.
Driving gene expression in identified cell types using viral
vectors. a) In L7-Cre mice, cell bodies (Pkj), molecular layer
dendrites (ml), and white matter axons (wm) of Purkinje cells
express YFP following virus injection. Note the absence of
fluorescence in the granule cell layer (gc). b) In Gabra6-Cre
mice, the same virus drives YFP expression in granule cell
bodies (gc) and their axons in the molecular layer (ml), but not
the Pkj cell layer and white matter.
26/27
Rui M. Costa
Neurobiology of Action
Group Members
Rosalina Fonseca (Clinical Research Fellow)
Albino Maia (Clinical Research Fellow)
Rodrigo Oliveira (Postdoctoral Fellow)
Gabriela Martins (Postdoctoral Fellow)
Catherine French (Postdoctoral Fellow)
Cristina Afonso (Postdoctoral Fellow)
Fatuel Aguilar (Postdoctoral Fellow)
Visualization of different basal ganglia circuits using a
reporter line. The ROSA26-YFPreporter mouse line was
crossed with an RGS9L-cre line. The striatum and its
projections toglobus pallidus and substantia nigra reticulata
are visualized in white. For contrast, immunoreactivity
for parvalbumin labeling heavily cortex, thalamus and
hippocampus is depicted in red. Scale bar = 100um.
Vitor Paixão (Postdoctoral Fellow)
Eduardo Ferreira (PhD student)
Projects:
Pedro Ferreira (PhD student)
Fernando Santos (PhD student)
Neural mechanisms of skill and sequence
Ana Mafalda Vicente (PhD student)
learning
Ana Maria Vaz (Research Technician)
Understanding how novel actions are learned and
consolidated as sequences of movements and skills
are the main aims of this project.
Research Summary:
We are interested in the neural bases of action
We have uncovered neural activity in basal
in health and disease. Our overall goal is to
ganglial circuits that are related to the learning
understand how changes in molecular networks
and execution of sequences of movements. We also
in the brain modify neural circuits to produce
used optogenetics to identify and manipulate the
experience-dependent changes in actions. We
neurons mediating this activity.
are
particularly
interested
in
investigating
the corticostriatal mechanisms underlying the
Corticostriatal mechanisms underlying goal-
learning and flexible use of actions, e.g. how
-directed actions and habits
novel actions and skills are learned, how they
are voluntarily initiated, how they can be used to
obtain particular outcomes, and how eventually
they can become automated and habitual. We
seek to investigate these problems using and
integrative approach spanning from molecules
to circuits, where we monitor and manipulate
the activity of molecules, neuronal circuits, and
behavior. We chose to implement this integrative
approach in mice because they combine the power
of genetics, a mammalian brain with layered
Our goal understands the difference in the brain
between intentional actions and habits or routines.
We have uncovered that the dopamine transporter
is a critical gate for habit formations; and also
that different corticostriatal circuits dynamically
interact during the shift between goal-directed
actions and habits.
Neural mechanisms underlying the generation
of novel actions
structures that can generate oscillatory activity,
This project aims to understand how new self-
the possibility of accurately quantifying simple
initiated actions are generated and how this ability
behaviors like action initiation and stereotypic
is hampered in Parkinson´s disease. We have deve-
skill learning, and also more elaborate behaviors
loped a new methodology to classify in an unbiased
like goal-directed actions.
manner different behavioral and neural states.
Inbal Israely
in synaptic weights within a dendritic branch.
Neuronal Structure and Function
We aim to determine whether competition for
proteins during synaptic plasticity can shape the
Lab Members
organization of inputs within a dendrite, leading
Yazmin Ramiro Cortés (Postdoctoral Fellow)
to the physical clustering of synapses. We also
Anna Hobbiss (PhD Student)
investigate whether the clustering of synapses
Ali Ozgur Argunsah (PhD Student)
can be observed following the development of
neural circuits, by examining the endogenous
distribution of spines within dendrites of the
Research Summary:
hippocampus.
We are interested in understanding how activity
can lead to specific structural changes in neurons
We find that the stimulation of multiple spines
which may be important for learning, and how
closely together in time can lead to competition
such changes affect connectivity within neural
for cellular resources, and that new proteins
circuits. It is unknown how the diverse forms of
are required for this process.
activity that a neuron receives are physically
demonstrate that synaptic plasticity may be
stored and regulated at the level of individual
biologically constrained, and provides a potential
spines, the sites of neuronal connections. Does
mechanism through which synapses could be
long lasting depression lead to structural changes
spatially clustered.
at synapses? What types of structural and
parameters over which competition is regulated,
electrophysiological modifications take place at
in order to define the learning rules for protein
spines following complex patterns of naturally
synthesis dependent plasticity.
These findings
We are examining the
occurring activity? Several mental retardation
disorders in humans are characterized by abnormal
spine morphology, and studying neurons from
animal models may further our understanding of
Structural correlates of synaptic depression at
dendritic spines
the relationship between structure and function.
Synaptic potentiation leads to an enlargement
We aim to combine molecular and genetic tools with
of spine head volumes at individual synapses,
imaging and electro-physiological methodologies,
however the structural correlates of synaptic
to determine how information is physically stored
depression are poorly understood.
in the brain.
depression can be initiated through a variety of
Long term
receptors, and it is unknown whether the structural
correlates of this form of plasticity apply generally
Projects:
Dendritic
to any decrease of synaptic weight, or whether
compartmentalization
of
protein
synthesis-dependent synaptic plasticity
there are specific modifications depending on
which signaling pathway is activated. We aim
to determine what are the structural correlates
We found that protein synthesis dependent
of synaptic depression at dendritic spines.
stimulation of spines can facilitate plasticity at
In particular, we are interested in exploring long
neighboring spines for up to an hour and over long
lasting forms of synaptic depression that depend
distances (70 um). Through 2-photon imaging and
on new protein synthesis. We will determine what
uncaging of glutamate at individual spines, we
are the parameters which govern these changes
aim to visualize structural changes that occur in
following activity at specific inputs. Additionally,
response to protein synthesis dependent forms of
we will probe whether new proteins serve to
activity. We will examine how activity at multiple
constrain plasticity at multiple spines similarly to
spines leads to structural changes and changes
the case for long term potentiation.
28/29
We have induced long lasting synaptic depression
through the activation of metabotropic glutamate
receptors (mGluRs) in hippocampal organotypic
slice cultures. We have quantified the structural
changes which correlate with this form of plasticity
through 2-photon imaging of subsets of spines
for up to four hours. Additionally, we recorded
electrophysiological responses from these cells in
order to monitor the changes following synaptic
plasticity.
Plasticity consequences of naturalistic spike
trains at single synapses
Naturally occurring patterns of activity are complex in structure and have an irregular distribution of action potentials.
Thus far, synaptic
Inducing activity at single dendritic spines to study
structural dynamics. Using 2-photon microscopy in living
brain slices together with photoactivation of caged glutamate,
we can examine how neurons physically store information
at synapses. We can vary the type of stimulation delivered at
a given input to mimic different forms of activity, and study
what are the structural and functional correlates.
We also examine how a neuron integrates information
arriving at multiple synapses.
Automatic
dendritic
spine
detection
and
analysis
plasticity at individual inputs has been assessed
The combination of live 2-photon imaging and
through delivery of regular patterns of activity.
glutamate uncaging allows us to investigate how
We aim to mimic the varied input patterns
neuronal structure and function are correlated at
observed in vivo with glutamate uncaging at
the level of individual spines following synaptic
individual spines, in order to determine what are
activity.
the structural and plasticity correlates of these
of the spine head, many other changes in spine
forms of activity. We will determine how such
structure have been observed, for example,
complex trains of activity interact across multiple
changes in the length of the spine neck. Such
synapses within a dendritic branch. We will use
changes are difficult to quantify with existing
this information to model neuronal information
methodologies, and therefore we aim to develop
processing in order to develop an understanding
automated data analysis tools for handling both
of the learning rules which govern synaptic weight
the large data sets and the many variables to be
changes.
analyzed. We aim to achieve greater precision
In addition to changes in the volume
and flexibility in the quantification of structural
We have established a collaboration in order to
changes, as well as to significantly enhance the
obtain in vivo electro-physiological recordings
efficacy of data analysis.
from hippocampal CA3 neurons. Experiments in
which electrophysiological recordings are coupled
Thus far, we have developed an automated, multi-
with 2-photon imaging in hippocampal organo-
level, region based segmentation method to detect
typic slice cultures are underway in order to
dendritic spines from two-photon laser scanning
monitor the structural and plasticity correlates
microscopy images. Identified structures in two-
of spike timing dependent plasticity. This form
photon images of dendritic spines are used to
of plasticity depends on the integration of events
train the segmentation algorithm. This is the first
at single inputs, similarly to what is observed
step towards a broader automated dendritic spine
endogenously.
detection and analysis framework.
Adam Kampff
data stream generation processes and devices,
Intelligent Systems Lab
such as cameras, microphones and other data
acquisition systems. Combinators provide ways
Lab Members
to transform, filter, and otherwise manipulate
Gonçalo Lopes (PhD Student)
these asynchronous data streams. We present
the general architecture of Bonsai as well as the
Research Summary:
currently available packages for computer vision,
audio and signal processing, data acquisition
The goal of the Intelligent Systems Lab is to
and instrument control. We also demonstrate
understand how a nervous system constructs a
several practical applications of the framework
model of the world. How do brains learn about
to the design of paradigms commonly used in
the statistics of their environment? How is this
experimental neuroscience.
information encoded in networks and used to
control intelligent behavior? To answer these
fundamental questions, two major technical
advances must occur:
1. The development of virtual worlds in which the
statistics and physics of the environment can be
manipulated, providing experimental control over
the model formed by an animal’s nervous system.
2. The design and construction of novel devices for
simultaneously recording from large populations
of neurons throughout the brain of a behaving
animal.
My research group strives to address both of these
problems.
Performance data from one rat during the shuttling task
before and after unexpected changes to the environment. The
blue vertical line indicates the beginning of environment
manipulations. Different colors indicate distinct sessions.
Moving with motor cortex: A fine-scale analysis of
rodent behavior in unpredictable environments
Mammals excel at using statistical regularities
Projects:
Bonsai: A general purpose data stream processing framework for experimental neuroscience
to predict their environment, but the neural
algorithms and representations underlying this
ability to learn and use a predictive model are far
from understood. In order to study this question
in rodents, we designed a “modular” shuttling
Modern techniques in experimental neuroscience
paradigm. In this task, rats are alternately rewarded
require the combination of many different
at opposite ends of a U-maze and their crossings
technologies and software algorithms for data
recorded using high-speed, high-resolution video.
acquisition, analysis and instrument control.
The walls and floor of the maze are composed of
The development of such systems is often a time-
modular elements outfitted with programmable
consuming and challenging task. We present
sensors and actuators, the rules of which specify
Bonsai, an open-source framework for rapidly
the statistics of the environment. We performed
prototyping and composing asynchronous data
a systematic exploration of behavior in non-
stream processing workflows, which is built
stationary environments and identified fine-scale
on top of the Reactive Extensions for the .NET
metrics that will be paired with electrophysiology
framework. The development of a Bonsai workflow
and lesion studies in cortical motor areas. Here
revolves around two simple concepts: sources
we present the assay design and behavior data
and combinators. Sources represent different
collected during crossing of a series of obstacles,
30/31
some of which change their configuration on a
commonly used for extracellular recording may
trial-by-trial basis. We show how rats quickly
be sub-optimal for detecting and isolating the
learn to navigate this environment and provide a
activity of neurons in the vicinity of the probe. We
detailed characterization of behavioral responses
are thus investigating novel electrode materials
to unpredictable reconfigurations.
and structures, aiming to improve the electrodetissue interface, optimize the SNR, and increase
Nanostructuring strategies for improving the
selectivity for dense signals. We used material
performance of neural electrodes
processing techniques to make “nanostructural”
changes to the microelectrode: a focused ion-beam
Extracellular electrical recording of neuronal
(FIB) with 10 nm resolution and surface deposi-
activity
for
tion of metallic oxides and conductive polymers.
understanding the function of nervous systems.
The effects of these structural and surface
However, major discrepancies have been observed
modifications were first verified by impedance
when the signals detected with extracellular
and cyclic voltammetry measurements. We then
electrodes are compared to those recorded with
evaluated the performance of the modified devices
other techniques (e.g. functional imaging). We
during acute recordings from mammalian brain
hypothesized that the smooth, metallic surfaces
structures.
is
an
important
technique
Susana Lima
Specific Aim 2. Investigate the contribution of
Neuroethology Laboratory
different neuronal populations within the VMN
using optogenetic tools.
Lab Members
Léa Zinck (Postdoctoral Fellow)
Specific Aim 3. Test the causal relationship
Kensaku Nomoto (Postdoctoral Fellow)
between the activity observed and the different
Susana Valente (Student)
neuronal populations using optogenetics.
Vanessa Urbano (Technician)
We found gender-responsive VMH neurons, in
Research Summary:
agreement with a previous study in the VMH of
male mice. Furthermore, our results showed that
The main goal of our laboratory is to gain mecha-
the proportion of male-inhibited neurons during
nistic insights into the neuronal processes under-
proestrous (7/22, 32%) was higher than those
lying fundamental behaviors in females: the choice
during the estrous and diestrous (5/34, 15% and
of a suitable mate and how to initiate and terminate
4/33, 12%, respectively). These results suggest that
sexual behavior. To do so, we use mice as model
changes in the balance of excitation and inhibition
system and a combination of approaches that
in VMH neurons may underlie behavioral changes
include physiological, anatomical and molecular
across the estrous cycle.
tools to dissect the contribution of candidate brain
areas to the emergence of these natural behaviors.
Our long-term goal is to investigate if (and how)
Assortative Mate Choice
mates of different attrac-tiveness differentially
Along with finding food and avoiding predators,
modulate the course of a sexual interaction.
selecting sexual partners is one of the primary
functions of the brain. Choices serve a variety
Projects:
Female Receptivity and the Hypothalamus
of functions, from avoiding familial inbreeding
to avoiding inter-species mating, all of which
generally serve the goal of maximizing the fitness
of the resulting offspring and thereby providing
Female rodent behavior is heavily influenced by
the best investment of ones genes. Our goal is to
sex hormones. While, for example, females are
understand the neural mechanisms underlying
sexually receptive during proestrous phase, they
this fascinating behavior. Very little is known
reject copulation during all other phases of the
about how the criteria for mating are represented
reproductive cycle. It is well accepted that the
in the brain, how the decision-making process
ventromedial hypothalamus (VMH) plays a critical
works, how it is influenced by internal state. In
role in the control of sexual behavior. However
order to study those processes it would be ideal
it is unclear how the orchestrated activity of
to reproduce mate choice in the laboratory under
neurons in the VMH mediates behavioral changes
controlled, repeatable conditions. Inspired by the
across the estrous cycle in neurophysiological
natural situation of the hybrid zone between the
terms. Our hypothesis is that activity within
two subspecies of house mouse, Mus musculus
the VMN is underlying the sexual receptivity
musculus and Mus musculus domesticus, we
changes observed in females across the estrous
have developed a behavioral paradigm to study
cycle. To test this, our aims are:
assortative mate choice in the lab.
Specific Aim 1. Record the electric activity of
We have established a mate choice paradigm
single neurons in the VMN of freely behaving
with M. m. musculus and M. m. domesticus, where
females.
musculus females exhibit a strong and reliable
32/33
The graph in pannel A shows the results of limited contact experiments, where musculus females can choose between spending time
with a musculus or a domesticus male. As shown, musculus females prefer to spend their time interacting with musculus males, and
this preference is stable because if the same females are retested on a subsequent session 3 days apart, the preference is maintained
(Paired t-test: ***p<0.001 (N=54). In pannel B we have the electrophyisiological response of a single neuron in the female´s
ventromedial hypothalamus in response to female or male stimuli. This particular neuron is inhibited during contact with male.
The activity of the neuron is aligned to the contact of the stimulus female to the focal animal.
preference for their own subspecies. We have also
by mechanoreceptors present in the cervix and
established that this preference is influenced by
clitoris) is relayed to the brain and is important
early imprinting mechanisms and it increases with
for the rewarding effects of copulation and for its
multiple testing. Furthermore, the preference for a
termination. Despite being a fundamental aspect of
specific male is not absolute, but rather flexible and
sexual behaviour, very little is known about how the
dependent of the alternatives that are available.
brain integrates the genital stimulation received
Papers in preparation: A reliable paradigm to study
during copulation and how the brain might use this
assortative mate choice in the laboratory. Zinck,
information to inhibit further sexual arousal. Urbano and Lima; Assortative mate choice in the
house mouse is learned during early life.
We have started by establishing a protocol to trace
the genital input to the brain, by using pseudo
Female sexual behaviour: neuronal pathways
for arousal termination
rabies viruses (PRV) expressing green fluorescent
protein. PRV infects axon terminals of neurons
and after infecting a neuron, jumps to synaptically
Like all behaviours, sexual arousal has a begin-
connected neuronal partners. By employing this
ning and an end during the course of a normal
method we are investigating which brain areas
sexual interaction. Sensory genital stimulation
are synaptically connected to the genital organs
received by the female during copulation (sensed
that receive stimulation during copulation.
Christian Machens
prediction error (membrane potential) exceeds a
Theoretical Neuroscience Lab
certain value. These assumptions naturally explain
several mysterious properties of neural systems,
Lab Members
such as the tight balance between excitation and
Pedro Goncalves (PhD Student)
inhibition, and irregular, asynchronous firing.
Florian Dehmelt (PhD Student)
We are specifically interested in the oculomotor
Wieland Brendel (PhD Student)
system, which controls eye position.
Nuno Calaim (Technician)
We have made progress in understanding the
Research Summary:
main properties of the networks developed under
the new assumption. A paper has been written
We construct mathematical theories to understand
and is currently in revision: Boerlin M, Machens
the operation of the brain. Our main interest lies
CK, Deneve S (2012). Balanced spiking networks
in understanding how the millions of neurons
can implement linear dynamical systems with
inside the brain coordinate their activity to make
predictive coding.
sense of the world and create behavior. Whereas
many experimental labs address the question by
measuring the behavior of animals, the electrical
Analysis of neural population data
activity of neurons, or the anatomical details of
Higher brain areas receive inputs from many
neural connectivity, our main aim is to put order
parts of the brain. The activity of neurons in these
into these observations using the language of
areas often reflects this mix of influences. As a
mathematics. To this end, we collaborate closely
result, neural responses are extremely complex
with experimental labs recording from thousands
and heterogeneous, even in animals performing
of neurons and develop methods to visualize and
simple tasks. In this project, we analyze neural
interpret these recordings. We form theories of
population data and develop new data analysis
the computations implemented by neural circuits
tools to understand neural population recordings.
based on optimization principles and apply these
We specifically follow probabilistic approaches,
theories to the recorded data. We also construct
in which the goal is to characterize a (multi-
neural network models designed to elucidate the
variate) probability distribution that represents
circuit mechanisms underlying the measured
the likelihood of finding a given neural response
behaviors.
in a specific area. Our study of the population
response in the PFC of monkeys and rodents
Projects:
Spiking network dynamics
during 2AFC tasks suggests that independent
inputs like time, stimulus and reward are
consistently represented in separate orthogonal
subspaces.
Neural networks are capable of performing an
incredible variety of difficult tasks, but how
We have continued analyzing data and recruited
they manage to do this is poorly understood.
new collaborators. We have finalized a new method
We study how spiking neural networks can
for the analysis of population data (“Demixed
implement arbitrary linear dynamical systems---
principal component analysis”, published in the
these encompass a huge variety of computations.
NIPS proceedings) and have submitted a review
We follow an approach in which the membrane
which is currently under revision: Wohrer A,
potential of a neuron is reinterpreted as a
Humphries M, Machens CK (2012). Population-
‘prediction error’ between a network’s actual
wide distributions of neural activities during
and desired output. Neurons only fire when this
perceptual decision-making tasks.
34/35
The role of time in behavior
Reinforcement Learning in its classical setting is
based on Markov Decision Processes which assume
discrete state representations and transitions.
When time, an intrinsic continuous quantity, becomes a relevant variable for the learning process
this discrete setting becomes inadequate. We use
continuous reinforcement learning to model a classical conditioning paradigm of trace conditioning,
where reward is given at a fixed time interval after
a cue presentation. In this paradigm, the timing of
reward delivery becomes a relevant variable for the
learning process. We study how the agent can learn
the timing of the reward, given that the tracking of
time is uncertain. We assume that the perceived time
evolves according to a stochastic (drift-diffusion)
Illustration of demixed principal component analysis (DPCA).
A central problem in understanding activity in the brain
is that neurons often mix information, especially in
higher-order areas. If an animal is engaged in a task that
involves a stimulus, a decision, and a time interval between
the two, then each neuron will generally represent a different
amount of information about the stimulus (yellow), the
decision (green), and the time (blue). Given that brain areas
consist of millions of neurons, thousands of which can be
recorded with modern-day technique, the complexity of these
mixtures severely impedes our ability to understand what
the respective area is computing or contributing to the task.
We have developed a new method (DPCA) that allows us to
represent this data in a far more compact format, using only
a few components (or ‘representative cell responses’) that
demix the information about the relevant task variables
as much as possible.
process. We discuss different scenarios of how
learning could work under these constraints, and
commands into position signals to maintain
compare the resulting behavioral predictions.
stable eye fixations after saccades. Previous
Control of cerebral energy metabolism
electrophysiological and pharmacological investigations of the system have shown that neurons
Maintaining homeostatic ATP concentration in
in the OI have firing rates that can persist at a
brain tissue is a major challenge to an organism,
continuum of levels, with each level corresponding
and failure results in neuronal injury and possible
to a particular fixation. These findings have led
neurodegeneration. Nutrients required for ATP
to the hypothesis that the OI has a continuum of
synthesis are extracted from blood, and changes
stable stationary states, giving rise to a continuous
in blood flow and oxygenation correlate well with
attractor network. Here we test this hypothesis
changes in neural activity. While action potentials
by performing optogenetic perturbations in the
can be generated with remarkable efficiency, it is
OI of zebrafish expressing halorho-dopsin (or
not known whether this parsimony is mirrored by a
channelrhodopsin). The resulting instantaneous
similarly efficient regulation of blood flow. To quantify
eye movements confirm that the system features
its contribution to the cost of energy homeostasis,
continuous attractor dynamics, and suggest
we are studying a minimal metabolic model linking
previously unsuspected dynamics around the
metabolite supply from blood to ATP synthesis in
attractor after channelrhodopsin stimulation.
brain tissue. The model incorporates both oxidative
These results pose new constraints on the
and a non-oxidative pathways consuming glucose,
circuit connectivity of the system, and highlight
oxygen and pyruvate, and accounts for the removal of
the potential of the combination of optogenetics
waste products such as carbon dioxide. Preliminary
with theoretical models to unveil neural circuit
results predict that the metabolic supply observed
dynamics.
experimentally represents the fastest possible
return to homeostasis.
Dynamics of an oculomotor integrator revealed
by instantaneous optogenetic perturbations We have finalized both theory and data analysis.
A paper is currently under preparation and
should be submitted soon: Goncalves P, Arrenberg
A, Baier H, Machens CK (2012). Dynamics of an
The oculomotor integrator (OI) in the hindbrain
oculomotor integrator revealed by instantaneous
transforms incoming horizontal eye movement
optogenetic perturbations.
Zachary Mainen
Systems Neuroscience Laboratory
Lab Members
Projects:
Optogenetic
identification
and
control
of
serotonin neurons in behaving animals
Enrica Audero (Postdoctoral Fellow
Serotonin (5-HT) is an important neurotransmitter
& project manager)
implicated in a wide variety of physiological
Cindy Poo (Postdoctoral Fellow)
functions and psychopathologies, but whose
Eran Lottem (Postdoctoral Fellow)
function is not well understood. Critically, very
Eric Dewitt (Postdoctoral Fellow)
little is known about the activity of serotonin-
Magor Lorincz (Postdoctoral Fellow)
releasing neurons in the brain. This problem is
Hope Johnson (Postdoctoral Fellow)
greatly exacerbated by the difficulty in identifying
Masayoshi Murakami (Postdoctoral Fellow)
these neurons during physiological recordings.
Guillaume Dugué (Postdoctoral Fellow)
To address these problems, we will develop and
Niccolò Bonacchi (PhD Student)
validate optogenetic methods that target 5-HT
Ana Rita Fonseca (PhD Student)
neurons, gaining access to record and perturb
André Mendonça (PhD Student)
this system optically with high temporal and
Maria Inês Vicente (PhD Student)
genetic specificity. We will combine these tools
Patricia Correia (PhD Student)
with behavioural analysis and electrophysio-
Sara Matias (PhD Student)
logical recordings toward understanding the
Gil Costa (PhD Student)
role of 5-HT in adaptive behaviour. Our aims
are to use these approaches to stimulate, silence
Research Summary:
and monitor 5-HT function in the context of
spontaneous behaviours, value-related decision-
We are interested in understanding the principles
making, sensorimotor function and behavioural
underlying the complex adaptive behaviour of
timing.
organisms. Starting with quantitative observations of animal behaviour, we aim to integrate
We
quantitative cellular and systems level experi-
stimulating light-gated channelrho-dopsin-2 in
mental analysis of underlying neural mechanisms
5-HT neurons, using slice physiology, pharma-
with theoretical, ecological and evolutionary
cology, microdialysis, in vivo recordings and
contexts. Rats and mice provide flexible animal
demonstrated a light-activated field potential as
models that allow us monitor and manipulate
a measure of 5-HT stimulation (manuscript in
neural circuits using electrophysiological, optical
preparation). We found effects of 5-HT stimulation
and molecular techniques. We have made progress
on olfactory neural activity in the piriform cortex.
using highly-controlled studies of a simple learned
We demonstrated a new system for chronically
odor-cued decision task and are extending our
monitoring neural activity in genetically-defined
focus toward more complex behaviours. Projects
neuronal populations.
continued
to
validate
techniques
for
in the lab are wide-ranging and continually
evolving. Current topics include (i) olfactory
sensory decision-making, (ii) the function of the
serotonin system, (iii) the role of uncertainty
Olfactory objects and decisions: from psychophysics to neural computation
in brain function and behaviour, (iv) the neural
Object recognition is an important and difficult
dynamics of choice.
problem solved by the nervous system. According
to theoretical accounts, object recognition can
be understood as a process of probabilistic
inference. Under this hypothesis, complex stimuli
36/37
are represented using a probabilistic population
code. To link these normative ideas to specific
neurophysiological and behavioural predictions,
we are formalising them using computational
models. Experimen-tally, our primary goal is to
monitor and perturb object representations in
the functioning, compu-ting brain. To this end,
we deploy olfactory psychophysical tasks in rats,
which formalise complex real-world problems. By
combining such quantitative paradigms with largescale neural ensemble recordings in the olfactory
cortex, we can study how populations of neurons
encode and process complex odor scenes, attempt
to account for behavioural performance, and test
the predictions of our theoretical models.
We compared speed-accuracy trade-offs (SATs)
in odor detection and categorisation and found
large differences between tasks, demonstrating
that SAT is problem-specific and suggesting
that the locus of performance-limiting noise is a
critical variable (manuscript in preparation). We
developed a computational model of these tasks,
which can be fit to the data, and which has allowed
us to formalise these hypotheses.
Action selection and action timing in the
premotor cortex
Executing the right action at the right moment is
important for adaptive behaviour. Thus, not only
how we choose one action among multiple options
The role of the neural ensembles in the frontal cortex in
deciding when to give up waiting (M. Murakami).
(Top) The behavioral task used to study waiting time. A
trial begins with a rat inserting its snout in a nose poke
and waiting for two tones. If it succeeds in waiting for the
second tone, which has a long delay, then it gets a large water
reward; if it gives up before tone two it gets only a small
reward. In these conditions, rats give up waiting at random
times between the first and second tone (not shown). (Bottom)
The dynamics of activity representing a population of 188
frontal cortex neurons during the waiting period. Activity
was averaged over a group of trials with similar waiting
time (as indicated by the color code) and principal component
analysis was used to reduce the number of dimension into
two (PC1 and PC2). Tic marks on each trajectory indicate 150
ms time intervals and arrows indicate the direction of time.
Notice that trajectories all begin within a tightly defined
region corresponding to initiation of waiting and end within
another region corresponding to the initiation of withdrawal
from the nose poke. With increasing waiting time, the
trajectories formed larger arcs between these subspaces.
but also how we determine the timing of actions
are fundamental questions.
the motor cortex. Furthermore, by analyzing the
relationships of spiking activity amongst multiple
Our goal is to understand what features of future
neurons, we hope to gain insight into computations
actions are represented in the neuronal firing
within the microcircuits in the motor cortex.
patterns in these areas, and how the interaction
Finally, we will apply optogenetic techniques to
between neurons gives rise to the action selection
perturb specific circuits and observe the impact
and action timing processes.
on behaviour.
To achieve this goal, we are using multiple single-
We analyzed neural correlates of action timing in
unit recording techniques in behaving rodents.
the preomotor cortex, documenting two classes of
By correlating the activity of neurons with the
waiting-time predictive neurons and a dynamical
animal’s behaviour, we are seeking to understand
systems
the internal representation of future actions in
(manuscript submitted). We also developed a
analysis
of
the
ensemble
activity
task in which we can manipulate the availability
in the course of decision-making is computed
of potential action options. We began testing
in olfactory sensory cortex. We are currently
optogenetic interventions in these contexts.
establishing similar confidence-reporting tasks in
humans and testing them in a range of behaviours.
Evaluating the reliability of knowledge: neural
mechanisms of confidence estimation
These experiments will give us further insights
into the nature of the neural processes underlying
confidence estimation.
Humans and other animals must often make
decisions on the basis of imperfect evidence. What
In rats, we used chronic multi-electrode recordings
is the neural basis for such judgments? How does
to assay neural ensemble function in the olfactory
the brain compute confidence estimates about
tubercule
predictions, memories and judgments? Previously,
reporting task (study in progress). We also found
we found that a population of neurons in the
that inactivation of the rat orbitofrontal cortex
orbitofrontal cortex (OFC) tracks the confidence
impairs confidence reporting but not choice
in decision outcomes. We are seeking to extend
behaviour (manuscript under review). In humans
these observations by testing whether confidence-
we tested confidence reporting tasks similar to
related neural activity in the OFC is causally
those we deployed in rats under several different
related to confidence judgments. We are also
psychophysical paradigms.
addressing how the uncertainty about a stimulus
of
rats
performing
a
confidence
38/39
Marta Moita
We have tested the role of contextual learning in
Behavioural Neuroscience
auditory trace fear conditioning. We found that
decreasing the saliency of the training environment
Lab Members
disrupts learning to fear a tone that precedes
Ema Alves (Postdoctoral Fellow & Lab manager)
shock by several seconds and that inactivating
Cristina Marquez Vega (Postdoctoral Fellow)
the hippocampus does not decrease it further.
Marta Guimarãis (PhD student)
In addition we are studying the role prefrontal
Ana Pereira (PhD student)
cortex in trace conditioning by performing single-
Scott Rennie (PhD student)
unit recordings in this structure during learning.
Andreia Pereira (PhD student)
Elizabeth Rickenbacher (PhD student)
Research Summary:
Cooperation in social dilemmas in rats
Game theory has constituted a powerful tool in
the study of the mechanisms of reciprocity. Having
We are interested in understanding the neural
shown that, in a Prisoner’s Dilemma game, rats
mechanisms underlying behavioural plasticity
shape their behaviour according to the opponent’s
using a combination of behavioural, pharmaco-
strategy and the relative size of the payoff resulting
logical, molecular and electrophysiological tools.
from cooperative or defective moves, we now aim
In particular, we are studying how prior experi-
at dissecting the mechanisms.
ence and how social interactions shape behaviour. To this end, we are studying fear; both how
We tested whether rats learn to coordinate in a
animals learn to fear cues that are predictive of
game where coordination with a conspecific leads
aversive events or threats, and how fear can be
to highest number of rewards. We have found that
socially transmitted, i.e. how animal respond to
rats learn to coordinate and that they are not
the distress of con-specifics. We chose fear lear-
simply following the other rat, since decreasing
ning since it is conserved across species, entai-
the reward for coordinating leads to a significant
ling fast robust learning and very long lasting
decrease in coordination.
memories. We are also studying decision-making
in the context of social interactions, using game
theory to test how rats learn and evaluate the
payoffs that result from the interaction with
another individual.
Neural mechanisms of social transmission of
fear in rats
This project aims at investigating the mechanisms
underlying social transmission of fear (STF) in
Projects:
Neural Mechanisms of trace auditory fear
conditioning
This project focuses on the role of different memory
rats, i.e. how rats respond to the fear displayed
by a con-specific. In order to unravel the neural
circuit underlying STF, we will first determine
how prior self-experience with shock contributes
to STF and what are the sensory cues that mediate
this process.
systems in trace auditory fear conditioning (tAFC).
We hypothesized that the mechanism underlying
We found that rats do not rely on visual cues,
the association between a tone and a shock depends
alarm calls or short range chemical signals to
on the length of the trace interval memory and
detect fear in a conspecific. Instead, they use
in the case of long intervals they rely on episodic
auditory cues which are likely to signal the
memory between the two stimuli, where in the case
sudden transition from motion to immobility.
of a short interval rats rely on working memory.
Through sound playback experiments, we found
that the absence of movement-evoked sound was
necessary and sufficient to induce fear in rats. In
addition we have found that prior experience with
shock is necessary, but not sufficient for vicarious
fear.
Social Buffering of Fear
Social interactions can decrease anxiety and
fear in a variety of circums-tance, a phenomenon
known as social buffering. Even though oxytocin
has been implicated in this process, its underlying
neural mechanisms remain poorly understood.
We use auditory fear conditioning, during which
an animal can learn to fear a neutral tone when
it is paired with aversive footshocks, to test the
effect of social buffering on fear conditioned rats.
Our goal is to test whether social interactions
decrease conditioned fear responses in a lasting
manner and to unravel the neural mechanisms of
this process.
Rats in a maze.
We conditioned rats to fear a tone and the next
day, we exposed them to the tone in the presence
that non-human primates engage in this form of
or absence of their cagemate. We found that rats
cooperation, provided the recipient of help displays
tested in the presence of their cage-mate showed
clear signals of intention. Moreover, rats respond
less freezing than if tested alone. In addition, when
to the distress of a restrained conspecific by
tested again, now alone, rats that were previously
opening the restrainers’ door. We aim to establish
exposed in the presence of their cagemate still
a paradigm to study prosocial behavior in rats that
froze less than the ones exposed alone showing
allows the dissection of the motivations that drive
that social buffering has long lasting effects on
rats to help a conspecific and the investigation of
fear. Finally, we are currently testing the role of
the underlying neural circuits.
oxytocin in the central nucleus of the amygdala
(CeA), a major output station that controls several
We developed a new behavioural task to measure
defense responses. Preliminary data suggests that
the ability of rats to cooperate, when the decision
blocking oxytocin in CeA blocks the immediate and
to cooperate does not involve a direct reward to
long lasting effect of social buffering on freezing.
the focal animal, and with no interference of stress
on the cooperating animals. Rats were trained
Prosocial behavior in rats
in a double T-maze, where the animals have to
nose-poke to access the rewarded arms. The focal
Most of the studies on cooperation until now used
rat has the opportunity to choose to reward a
tasks that focus on cooperative acts where the
conspecific or not, depending on the arm where
focal animal obtained a benefit for cooperating.
it nose-pokes. Rats engaged in this task showing
Even though the ability to help other individuals
high levels of cooperation, suggesting that rats can
in the absence of self-interest was thought to
show instrumental helping and might be sensitive
happen only in humans, it was recently shown
to vicarious reward.
40/41
Michael Orger
these simple responses can involve coordinated
Vision to Action
activity in hundreds of neurons distributed in
areas throughout the brain. We image the pattern
Lab Members
of neural activity in the brains of transgenic fish,
Claudia Feierstein (Postdoctoral Fellow)
which express a genetically encoded calcium
Sabine Renninger (Postdoctoral Fellow)
indicator in all of their neurons, while they track
Joao Marques (PhD Student)
visual stimuli with their eyes. Since this behavior
Simone Lackner (PhD Student)
is very repeatable, we can systematically record
Felix Ludwig (MSc Student)
responses from the whole brain with single cell
resolution. We determine what sensory or motor
Research Summary:
signals are represented at each point, by showing
stimuli designed to dissociate the two, such as
Our goal is to understand how the brain integrates
monocularly presented or binocularly conflicting
sensory information and selects and executes
gratings. Neuronal tracing using photoactivatable
appropriate actions. In particular, we aim to
GFP reveals potential connectivity of the circuit.
determine the organization and function of neural
These experiments will provide us with the most
circuits underlying visually guided behaviors. We
complete description, in a vertebrate, of the whole
use the zebrafish as a model organism because
brain neural circuit underlying a sensorimotor
it allows us to visualize and manipulate activity
behavior.
in neural circuits throughout a vertebrate brain.
As early as one week post-fertilization, zebrafish
display a rich repertoire of innate visual behaviors,
following moving patterns, avoiding predators
Understanding the Neural Mechanisms that
Control Swimming Speed in Zebrafish Larvae
and tracking and capturing live prey. With no
Animals often use distinct gaits to move
skull and transparent skin, the entire volume of
at different speeds, and this requires the
the brain can be imaged non-invasively in one
engagement of distinct neural circuits. Zebrafish
field of view, and many neurons are individually
larvae use different motor patterns, and recruit
identifiable from fish to fish. Our approach has
different spinal interneurons, during slow and
three main themes: 1) Quantitative analysis of
fast swimming. Currently, it is not known how
behavior. 2) Imaging of whole-brain neural activity
the brain computes desired speed or relays this
dynamics in the behaving animal. 3) Perturbation
information to the spinal cord. We have developed
of identified neurons to reveal their role in
a system to perform high-speed online analysis
generating particular responses. In parallel, we
of tail kinematics in freely swimming fish, while
are developing new genetic tools that allow more
presenting visual stimuli. We find that zebrafish
specific targeting of identified cell types.
will adjust their swim speed to track different
moving patterns, and they do this by switching
Projects:
Neural circuits underlying the optokinetic
response in larval zebrafish
between two discrete motor patterns. We intend
to discover the neural substrates responsible for
this behaviour by imaging whole brain neural
activity in restrained fish, during visually evoked
swimming at different speeds in a closed-loop
How neural circuits integrate sensory information
virtual
to produce appropriate actions is a fundamental
investigating the mechanisms of speed control
question in neuroscience. We aim to address this
in zebrafish larvae, from visual inputs to spinal
question using optokinetic behavior, reflexive eye
circuits, we hope to uncover general principles of
movements in response to whole field motion. Even
vertebrate locomotor control.
reality
environment.
By
thoroughly
From dusk till dawn – How zebrafish respond to
changes in illumination
Larval zebrafish show a wide range of innate
responses to spatial and temporal changes in
illumination, from rapid orientation and taxis
to sustained modulation of locomotor activity.
However, little is known about the underlying
neural circuits and how neuromodulators act on
them to alter locomotor behavior. Using highspeed video tracking in a custom-built arena
we quantitatively assess the fishes’ choice of
swimming behavior in response to visual stimuli
such as whole field luminance changes and local
light and dark patches. We aim to determine
the neural activity evoked by the same stimuli
using in vivo calcium imaging of transgenic
fish expressing genetically encoded calcium
indicators. In parallel, we are building a library of
short promoter sequences that target expression to
distinct neuronal types, with the aim of developing
a comprehensive set of transgenic driver lines.
These can be combined with different reporter
a) Zebrafish reticulospinal neurons. b) Custom 2-photon
microscope with integrated visual stimulation and
high-speed behaviour tracking. c) Micron resolution whole
brain functional imaging during optokinetic tracking.
zColor and intensity represent response
tuning and magnitude.
lines to, for example, optogenetically activate or
silence these populations, or record activity in the
reveal the cellular organization of these circuits
freely swimming fish using GFP-Aequorin.
and the dynamics of visual processing in response
to complex stimuli. We aim to: (1) generate driver
Circuit mechanisms of visuospatial processing
in the zebrafish brain
lines that target gene expression to specific cell
types within the fish visual system, (2) characterize
visual
response
properties
and
functional
Complex visual behaviours, such as capturing
topography within these populations and (3) analyze
moving prey or avoiding approaching predators,
the interplay between population activity in the
require animals to compute the location and salience
optic tectum and isthmic nucleus when the fish is
of different objects moving in 3 dimensions. These
presented with multiple visual targets. We further
computations depend on dynamic interactions
plan to apply optogenetic tools and laser ablations
between many interconnected visual areas in the
to interfere with defined units of the circuitry, and
brain. We use transgenic expression of optogenetic
determine the link between circuit computations
tools, and in vivo 2-photon functional imaging to
and behaviour.
42/43
Joseph Paton
expressing CRE in specific basal ganglia cell
Learning Lab
types, we plan to express light sensitive channels
and pumps in targeted locations within the basal
Lab Members
ganglia circuit. Stimulating these proteins with
Rui Azevedo (PhD student)
light during experiments will provide us with two
Gustavo Mello (PhD student)
potentially powerful pieces of data. First, we will
Gonçalo Lopes (PhD student)
be able to ask what type of cell we are recording
Sofia Soares (Technician)
from in vivo much more easily and in higher
volume than was available with older techniques.
Research Summary:
Learning to adaptively respond to cues in the
Second, we can test hypotheses about the role
of activity in specific populations of neurons for
timing behaviour.
environment that predict behaviorally relevant
events is critical for survival. However, in the
In the past year Rui Azevedo has activated
natural world, where animals are exposed to
dopamine neurons using optogenetics in brain
myriad sensory stimuli, learning the predictive
slices, and in behaving mice. He gained behavi-
value of cues is non-trivial. How do animals figure
oural evidence of successful activation by showing
out which cues are predictive, and of what? This is
that he could condition mice to prefer a particular
called the credit assignment problem. Conceiving
spatial location by illuminating tranfected neu-
of this problem as statistical inference in the time
rons specifically when mice entered a particular
domain offers a parsimonious account of animals’
region. He is currently training transgenic mice on
learning abilities. In other words, when cues occur
a timing task, and will test whether manipulation of
relative to meaningful events is what determines
dopamine neuron activity affects interval timing.
their information content, their usefulness, and
thus, whether they warrant learning about.
However, we still do not understand how the
brain might keep track of times. We aim to
Neurophysiology of time encoding in the rodent
striatum
reveal neural mechanisms for time by observing
Lesion, pharmacology, and genetic studies all
and manipulating neurophysiology in behaving
suggest that the ability to estimate the passage
rodents performing tasks that lead them to
of time on the scale of seconds to minutes is
estimate intervals.
produced in the striatum, a major input area of the
basal ganglia. Thus, we trained rats to estimate
Projects:
Optogenetic investigation of interval timing
in mice
time intervals and recorded from striatal neurons
as they behaved and asked how the passage of
time could be encoded in the firing patterns we
observed. In addition, the basal ganglia is thought
to implement reinforcement learning mechanisms,
In the past year, we have initiated a parallel
helping the animal learn how to act in response
set of timing studies in mice in order to take
to a given situation based on past experience.
advantage the increased molecular power of the
We sought to place the neural signals we recorded
mouse relative to the rat. We have trained mice on
into a computational frame work that reconciles
a classic temporal reproduction task, called the
interval timing and reinforcement learning. Towards
peak interval task, and are currently training mice
that end, we are developing a computational model
on the SFI task mentioned above. By combining
of interval timing that includes signals related to
viruses dependent on CRE recombinase activity
those we observe experimentally, but that also can
for expression of transgenes, with mouse lines
solve reinforcement learning problems.
We currently have a manuscript in the final stages
of preparation describing the neural signals
we observe during an interval timing task. We
are also actively extending these studies to
gain more continuous measures of the animals’
behaviour during our task. This will be important
for continuing to rule out behavioural sources of
variance in the firing of neurons we record.
Neurometric - Psychometric comparison of
interval timing performance
Tasks in which subjects must categorize sensory
stimuli whose characteristics are parametrically
Modeling rats’ behavior using mechanisms derived from
experimental data. Output of a timing model running on a
task that we have previously trained rats to perform.
At the top are scalable temporal basis functions that resemble
the activity profiles of neurons we have recorded in the
striatum of rats during this task. These are used as rate
functions to produce poisson spike trains.
These spike trains are then decoded to estimate time (blue
trace) and subsequently drive behavior (red threshold).
varied have been powerful tools for relating
neural processing to sensation in a rigorous
A tight correspondence between the animals’
and quantitative manner. We are applying the
behavioural
same approach to an unconventional sensory
encoding of time would suggest involvement of
modality, the ability to sense the passage of time,
those neural signals in the process of timing.
performance
and
the
neuronal
by training rats on a two alternative forced choice
interval timing task. We can derive quantitative
Thiago Gouvea has designed the behavioural
description of animals’ interval timing abilities
apparatus, programmed the behavioural control
via the fitting of psychometric functions to their
required for the task, and has trained four animals.
choice data and then compare this to the ability
We will soon be initiating neural recordings
of neural activity to encode the passage of time.
during task performance.
44/45
Leopoldo Petreanu
record the activity of cortico-cortical projections
Cortical Circuits
while the animal is engaged in behavioral tasks
that depend on these circuits.
Lab Members
Nicolas Morgensten (Postdoctoral fellow)
We also plan to characterize the connectivity
Tiago Marques (PhD Student)
and synaptic properties of identified neuronal
populations constituting FF and FB circuits using
Research Summary:
The neocortex plays a key role in sensory perception and higher cognitive functions. Our overall
goal is to understand the neural computations
underlying cortical function, focusing on the
functional role of cortico-cortical interactions.
optical circuit mapping methods.
Projects:
Optogenetic circuit mapping of long range
cortical interactions
Cortico-cortical projections either terminate in
A comprehensive characterization of the precise
the middle layers (feedforward inputs, FF) or
neuronal
innervate the lower and upper layers, avoiding the
circuits is necessary to understand their function.
middle ones (feedback inputs, FB). The fact that
Feedforward
these motifs are conserved across many cortical-
from layer 2/3 to layer 6. In contrast, feedback
connections suggests that FF and FB connections
connections terminate in all layers except layer
might have a common function across areas.
4. Thus, as the dendrites of cortical neurons
In order to address functional role of cortico-
usually span several layers, cortico-cortical axons
cortical connections in cortical computation we
can potentially make synapses with almost any
are studying the structure and function of these
neuronal type in the cortical column. However, as
circuits. Using novel optical methods we plan to
the overlap of axons and dendrites is not always a
types
constituting
connections
Lasers beams on the optical table of a slice physiology setup used for mapping cortical circuits.
cortico-cortical
terminate
mainly
good predictor of actual connectivity, connections
are developing head fixed behaviors that require
need to be probed with functional methods. Using
several interconnected visual areas. Head-fixed
channelrhodopsin-assisted
we
behavioral paradigms allow us to have precise
will identify the postsynaptic targets of afferents
stimulus control and motor readout over a large
from different cortical areas. By mapping the
number of trials with high repeatability. Head-
connections linking cortical areas we will test
fixed behaviors also facilitate experimental
whether stereotypical feedfoward and feedback
access for the manipulation and recording of
connections synapses with the same postsynaptic
neuronal activity. In particular, they allow us to
cell types throughout the cortex. During the second
perform optical recordings of neuronal activity in
half of 2011 we assembled a custom slice physiology
behaving animals. Using two-photon microscopy
setup with the required optics to perform laser-
and
scanning photostimulation. We started injecting
we will record specifically from FF and FB
viruses expressing channelrhosopsin in the mouse
projections by imaging afferent axons in their
cortex and performing our first circuit mapping
target area. Recordings cortico-cortical circuits
experiments.
together with precise measurements of sensory,
circuit-mapping
genetically-encoded
calcium
indicators
motor and behavioral variables will help us in
Optical recordings of feedforward and feed-
understanding the role of these connections in
back cortical connections in behaving animals
cortical computation
In order to address the functional roles of
During the second half of 2011 we have setup the
feedforward (FF) and feedback (FB) circuits we
hardware and software required to establish head
plan to record from cortico-cortical projections
fixed animals in visual tasks. We also started
in animals is engaged in behavioral tasks that
training animals and testing different head-fixed
depend on these circuits. Toward this goal, we
behavioral paradigms.
46/47
Alfonso Renart
and repeatable fashion. We are developing
Circuit Dynamics & Computation
auditory discrimination tasks built around a
basic sound localization paradigm, which can
Lab Members
easily and quickly be learnt by rodents. We record
Raimundo Leong (PhD Student)
the simultaneous activity of multiple neurons
Job van der Voort (MSc Student)
from the auditory cortex during performance of
these tasks in order to investigate questions such
Research Summary:
as the population structure of trial-to-trial variability and its relationship to the accuracy of per-
The overall goal of the lab is to identify generic
ception, mechanisms for invariant processing of
principles governing the dynamics of cortical cir-
auditory information, or the interplay between
cuits and the way in which they produce function.
feed--forward
We are interested both in identifying characte-
perception.
and
feed-back
influences
in
ristic signatures of population organization –
through recordings of the simultaneous activity
of
neuronal
populations
during
controlled
behavioral tasks – as well as in understanding
The dynamical basis of working memory in the
prefrontal cortex
mechanistically how these patterns of population
Actions, their consequences and the sensory
activity emerge – which we investigate by
stimuli that inform them do not occur simulta-
developing mathematical models of the underlying
neously, therefore the brain must hold repre-
neuronal circuits. Our current work involves
sentations online so that they can be integrated,
around two lines of research: sensory perception
a capacity known as working memory. Single unit
– with an emphasis on the relationship between
recordings in primates performing tasks with a
the response variability of sensory neurons and
delay period have shown the prefrontal cortex
the accuracy of perceptual discriminations – and
(PFC) to be a key brain area in this process. Based
working memory, with a focus on the mechanisms
on this data a rich conceptual framework relying
underlying the maintenance of information across
on the idea of dynamical attractors has been
time in the prefrontal cortex.
developed. However, key aspects of this framework
appear at odds with recent data and some
remain untested. In this collaborative project, we
Projects:
combine electrophysiology, quantitative anatomy,
Population dynamics during auditory perception
Although
anatomy
makes
it
certain
optogenetics and modeling to provide a dynamical
foundation of working memory in mouse PFC. Our
that
goals are: 1) to delineate the anatomical extent of
information processing in the brain is the result of
circuits underlying working memory; 2) to assess
the interaction of neurons organized in networks
the relative contributions of cellular vs. synaptic
spanning multiple spatial scales, our knowledge
mechanisms to the ongoing memory traces; 3) to
about the patterns of population activity associated
characterize the patterns of PFC activity at the
to specific computations and about the mechanisms
population level during memory maintenance
that generate these patterns in recurrent neuronal
and to quantify their dynamical stability through
circuits is very incomplete. We are interested
delicate optical perturbations and 4) to gain a
in the computations performed by local cortical
theoretical understanding of the mechanisms that
circuits during perception. We use the auditory
allow recurrent networks to generate long-lasting,
modality because rodents naturally use auditory
time-varying memory traces.
cues to guide their behavior and because it allows
us to deliver complex stimuli in a well-controlled
Carlos Ribeiro
these studies are providing us with a model and
Behaviour and Metabolism
an entry point for studying nutrient balancing
and value-based decision making at the molecular
Lab Members
level.
Ana Paula Elias (Lab Manager & Research
Assistant)
Neuronal mechanisms of nutrient choice
Laura Napal Belmonte (Postdoctoral Fellow)
We want to identify and analyze the neuronal
Pavel Itskov (Postdoctoral Fellow)
networks used by Drosophila to change the
Ricardo Benjamim Leitão Gonçalves (Postdoctoral
behaviour of the animal to allow it to find and eat
Fellow)
the required nutrients.
Samantha Herbert (PhD student)
Veronica Corrales (PhD student)
We have used genetic approaches to identify
Célia Modesto Baltazar (Research assistant)
neuronal populations which are required for
nutrient choices. Currently we are analyzing
the identified neuronal substrates for nutrient
Research Summary:
homeostasis to understand how these neuronal
We are interested in understanding how molecular
and
cellular
mechanisms
control
populations act to guide feeding decisions.
complex
biological processes at the level of the whole
organism. For this we are focusing on how the
internal metabolic state of the fruit fly Drosophila
Quantitative analysis of feeding behaviour in
Drosophila
melanogaster affects its behavioural decisions.
In collaboration with the laboratory of Aldo Faisal
Starting from novel behavioural paradigms we
at Imperial College London we use automated
use molecular genetic techniques to identify and
video analysis to quantitatively link genetics to
characterize genes and neuronal populations
feeding behaviour in the fruit fly. These studies are
involved in producing the appropriate behavioural
providing us insights into the behavioral strategies
response to a specific metabolic need of the fly.
used by the fly to maintain nutrient homeostasis
as well as their biological implementation in the
nervous system.
Projects:
Molecular mechanisms of nutrient choice
We want to understand how Drosophila knows
what type of nutrients it needs and which are
the molecular mechanisms used by the nervous
system to change the behaviour of the animal to
allow it to find and eat the required nutrients.
We have continued investigating how conserved
nutrient sensing pathways act in the nervous
system to control feeding. Furthermore analyzing
genes identified as being required for nutrient
choice in a neuronal whole-genome RNAi screen
we are investigating novel molecular mechanisms
mediating nutrient homeostasis. Taken together
48/49
and electrophysiological approach to determine
Innate Behaviour
how defined neural circuits and their activation
elicit specific behaviors.
Lab Members
Márcia Aranha (Postdoctoral Fellow)
Nélia Varela (Postdoctoral Fellow)
Ricardo Neto (Postdoctoral Fellow)
Dennis Herrmann (PhD Student)
Projects:
Female receptivity
Nuno Martins (MSc Student)
Genetic studies have elucidated how Drosophila
Joao Afonso (Research Technician)
male courtship behavior is specified and its circuit
Sophie Dias (Research Technician)
components are being dissected at a surprising
speed. The circuit of female behavior on the other
Research Summary:
hand has been largely uncharacterized. We use a
behavioral protocol that allows us to selectively
Animals exhibit behavioral repertoires that are
inactivate subsets of neurons in the adult flies
often innate and result in stereotyped sexual
only. We use this behavioral approach and combine
and social responses to their environment.
it with anatomical and functional dissection of
Innate behaviors do not require learning or
the circuit.
experience and are likely to reflect the activation
of developmentally programmed neural circuits.
We explored further the involvement of apterous
We are interested in the nature of defined
neurons (ANs) in receptivity: We verified that
neural circuits: how activation of circuits elicits
locomotion is unaffected, as well as the fly’s
specific behaviors. In complex organisms it
attractivness. We characterized the pattern of
has been extremely difficult to study a circuit
ANs. We have masculinized the neurons and seen
beyond the early stages of sensory processing.
no phenotype indicating that ANs are not sexually
Drosophila melanogaster is an attractive model
dimorphic. We have tested females that have
system to understand a circuit because flies
inhibited ANs for their egg laying. Egg laying in
exhibit complex behaviors that are controlled by
virgins is unchanged indicating that there is not
a nervous system that is numerically five orders
an activation of the postmating switch at least to
of magnitude simpler than that of vertebrates.
the full extent.
We use a combined behavioral, genetic, imaging
Photoactivation allows visualization of the neurons innervating the V glomerulus. A-Before photactivation; B-After photoactivation;
C- Schematic generated by automated filament tracing; D- schematic of the projection neuron that connect to lateral horn
and mushroom bodies.
Across species stress odor response
We have traced the neurons that innervate the
v glomerulus. We observed Three projection
Stressed Drosophila melanogaster release an
neurons connect solely with the lateral horn and
aversive odorant that elicits a robust avoidance
one projection neuron that connects additionally
response in test flies. Our data indicate that stress
to the Mushroom Body. This result suggests that
odor avoidance is not common to all Drosophilids.
the CO2 response can be modulated.
This behavioral difference bet-ween melanogaster
and some of its sister-species provides a powerful
We tested the response of seven Drosophilidae
frame-work, amenable to genetic, developmental
to CO2. We observe a salt and pepper variation
and anatomical dissection, to inves-tigate how
across the phylogenetic tree indicating multiple
evolution has shaped distinct responses to an
occurrences for gain/loss of behavior.
environmental cue.
50/51
ASSOCIATED RESEARCH GROUPS
Domingos Henrique
retinal neurons. Using transgenic mice carrying
Neural Development
mutant alleles of Dll1 or Dll4, we are dissecting
how these genes contribute for normal cell fate
Lab Members
specification in the retina. We are also addressing
how proneural bHLH genes act upstream of Dll/
Elsa Abranches (Postdoctoral Fellow)
Notch signaling to prime multipotent retinal
Evguenia Bekman (Postdoctoral Fellow)
progenitors (RPCs) into different fates. We have
Cláudia Gaspar (Postdoctoral Fellow)
found that different combinations of proneural
Sanja Ivkovic (Postdoctoral Fellow)
bHLH genes are expressed not only in RPCs but
Catarina Ramos (Postdoctoral Fellow
also in differentiating neurons, overlapping with
Aida Costa (PhD Student)
Dll4. Our working model is that the simultaneous
Ana Guedes (PhD Student)
expression of lineage-determination genes in
Sara Ferreira (Research Technician)
retinal neurons is central to their multipotent
character, with Dll4/Notch signaling acting to
Research Summary:
generate the observed spatio-temporal pattern of
neuronal specification in the developing retina.
Cell Fate and Cell Polarity within the vertebrate
embryonic neuroepithelium Our main interest is
to understand the molecular mechanisms that
regulate the genesis of neurons in vertebrate
The Key Role of the Dynamic Nanog Expression
in pluripotent stem cells
embryos. We believe that a better knowledge
Pluripotency in Embryonic stem (ES) cells
of these mechanisms is a pre-requisite for the
is controlled by a dedicated gene regulatory
development of cellular replacement therapies to
network, at the top of which function a core of
treat neurodegenerative diseases, with a significant
three transcription factors, Nanog, Oct4 and Sox2.
impact on human health. Our research focus on
Using a novel reporter mouse ES cell line, we
the molecular events that control the generation of
performed a quantitative, systematic and dynamic
neural stem cells in the embryo, how these cells are
analysis of Nanog expression in ES cells, at the
maintained, and how they give rise to the multitude
protein and mRNA levels. Our results offer further
of neurons that compose the adult CNS.
confirmation that NANOG levels correlate with the
degree of priming to differentiation shown by ES
Projects:
Understanding cell fate decisions in the
embryonic neural retina
cells. In addition, our analysis imply that NANOG
fluctuations are intrinsically driven and inherent
to the pluripotent state. Our data on Nanog protein
and mRNA heterogeneous expression in ES cells
is qualitatively and quantitatively explained in
In this project, our aim is to understand the
the framework of a fully stochastic model, where
molecular logics underlying the generation of
intrinsic noise combined with a positive feedback
neuronal diversity in the developing neural retina.
loop in NANOG regulation generates the observed
Lineage determination in the retina is governed
heterogeneity in expression levels. This model
mainly by cell-cell interactions, a process in
allows us to infer unanticipated features of Nanog
which Notch signaling plays a central role. Our
regulation and function in ES cells, suggesting
work focus on the function of two Notch ligands,
novel perspectives about how stemness emerges
Dll1 and Dll4, which are expressed in newborn
from the inner workings of the NOS circuitry.
Rui Oliveira
that mediate the effects of prior experience social
Social Neuroendocrinology Laboratory
experience on subsequent behavior (i.e. winner
and loser effects).
Lab Members
Sílvia Costa (Postdoctoral Fellow)
Leonor Galhardo (Postdoctoral Fellow)
Rodrigo Abreu (PhD student)
Social modulation of adult neurogenesis: cichlid
fish and zebrafish as study models
Ana Faustino (PhD student)
Social plasticity is predicted to rely on different
José Miguel Simões (PhD student)
neural plasticity mechanisms depending on its
Magda Teles (PhD student)
temporal expression. Transient and reversible
changes in social behavior driven by social
Research Summary:
experience and context are expected to depend on
functional synaptic plasticity (e.g. LTP), whereas
We are interested in understanding the neuro-
irreversible switches between discrete behavioral
endocrine mechanisms of social behaviour and
phenotypes driven by developmental processes in
how the social environment may feedback on the
response to environmental cues are expected to
neuroendocrine system. In particular we are inter-
rely on structural changes in the neural network
ested in the role of hormones as key physiological
underlying social behavior. In this project we
mediators underlying social plasticity.
are using both zebrafish and cichlid fish to
study how single vs. repeated sequential social
Projects:
Neurogenomics of social plasticity: rapid transcriptomic responses to social interactions
interactions affect adult neurogenesis at different
levels (proliferation, migration, differentiation,
functional integration) in the nodes of the neural
network underlying social behavior. In cichlid
fish, we are taking advantage of its well described
Social plasticity is a pervasive feature of animal
chemical communication system and of the fact
behavior. Animals must adjust the expression of
that we found high levels of both cell proliferation
their social behavior to the nuances of daily social
and neuropeptide levels (AVT, isotocin) in the
life and to transitions between life-history stages,
olfactory bulbs (OB), to study olfactory modulation
and the ability to do so impacts on their Darwinian
of neurogenesis and its regulation by neuropeptides
fitness. Social plasticity may be achieved by
in the OBs.
rewiring or by biochemically switching nodes of
the neural network underlying social behavior
in response to perceived social information.
Social learning in zebrafish
Therefore, at the molecular level, it depends on
Social information can be collected on first-hand
the social regulation of gene expression, so that
by directly interacting with other individuals, or
different neurogenomic states correspond to
by observing other behavioural agents (social
different behavioral responses and the switches
learning). In this project we are investigating
between states are orchestrated by signaling
the mechanisms of social learning in zebrafish
pathways that interface the social environment
by
and the genotype. We have been studying socially
learning mechanisms in different social contexts
driven changes in gene expression in the brain in
(observational conditioning of predator avoidance
relation to adaptive social plasticity, both in cichlid
vs. a classical fear conditioning paradigm; social
fish and in zebrafish. So far we have shown that
eavesdropping in the context of aggressive
the perceived outcome of social interactions has
encounters vs. stimulus enhancement; mate
a major impact in the brain transcriptome profile
choice copying vs. independent mate choice). The
contrasting
it
with
equivalent
asocial
52/53
comparison of the brain patterns of IEG expression
across these studies will allow to test if social
learning in different functional domains share
a common neural network, or if in contrast each
social learning type shares its neural mechanism
with that of its corresponding asocial learning
form. These comparisons are particularly relevant
since prediction error that is considered a learning
signal is not directly available when animals use
public information.
Cognitive appraisal and cognitive bias in
zebrafish
A central concept in social cognition is that what
trigger a response to a stimulus are not only its
intrinsic characteristics but rather the evaluation
of what that stimulus or event means to that
organism at that moment in time. Therefore, the
exactly same event may elicit different responses,
depending on the way it is appraised by different
individuals or by the same individual at different
moments in time. The involvement of appraisal in
the activation of the physiological and genomic
responses also opens the possibility for consistent
evaluation biases to occur (i.e. some individuals
Mechanisms of social plasticity: social living animals adjust
the expression of their behaviour to social information
collected in previous social interactions or by observing
others (A); the cognitive appraisal of this information
allows them to evaluate the stimulus/ event in terms of its
valence and salience that will be encoded in a distributed
neural network (B); at each node of this network (C) neurons
will change their neurogenomic state (D), that is, their
gene expression profile in response to the perceived social
information; changes of gene expression are triggered by
the activation of neuronal activity-regulated transcription
factors (e.g. p-CREB) that regulate immediate early genes
(e.g. c-fos) that can regulate synaptic proteins (E), therefore
modulating neural plasticity that underlies behavioural
flexibility.
will consistently evaluate ambiguous stimuli as
negative, and others as positive). Thus, cognitive
circuits underlying social behavior. In this scope
bias in the appraisal process can be a major factor
we are studying an intertidal fish (peacock blenny)
in individual variation in the susceptibility to life
where two developmental sequential male morphs
events. In this project we aim to uncover the genetic
occur that express divergent behaviours: female
pathways and neural circuits involved in cognitive
courtship behavior in young female-mimicking
appraisal and cognitive bias, using zebrafish
males vs. male courtship behavior in older
(Danio rerio) as a model organism. So far we have
territorial males. So far we have characterized
been developing behavioural assays (CPP, contrast
the neuroendocrine correlates of these alternative
effect test) to test cognitive appraisal in zebrafish.
mating tactics (i.e. circulating hormone levels,
levels of steroid receptors, neuropeptides and steroi-
Neurogenomic and physiological mechanisms
of adaptive behavioral plasticity in a fish with
male alternative mating tactics
dogenic enzymes in the brain, and the effects of
steroids and neuropeptides on tactic expression),
and the environmental cues that trigger the
expression of these conditional tactics. More
Species that present sequential alternative beha-
recently, we have deep-sequenced its transcriptome
vioral phenotypes so that the same individual
and we are now using RNA-Seq to compare
expresses opposite behaviors at different life-
alternative morphs and in order to identify the
history stages, are particularly well suited for
gene networks and signaling pathways underlying
studying the structural reorganization of neural
developmental social plasticity in this species.
FACILITIES AND PLATFORMS
Administrative Support
Transgenic & Rederivation Unit
The Administrative Office provides all the
Rubina Caldeira (Rederivation Unit)
necessary aid, in all the fields from social,
Joana Almeida (Transgenic Unit)
bureaucratic and technical, in order to ease the
integration of new members and to provide all
The chief mission of the Transgenic & Rederivation
the necessary tools for the researchers to fully
Unit is to provide support to the research work
perform their priority goal – scientific research.
of cancer and neuroscience investigators. The
unit provides services of strain rederivation,
Alexandra Piedade (Meetings and Courses)
cryopreservation, revitalization and production
António Coelho (Grants Manager)
of transgenic animals. Cryopreservation and
Philipp Tsolakis (Financial Manager / Controller)
Revitalization of both embryos and sperm
Raquel Gonçalves (Purchasing and Ordering)
are crucial services that, in addition to other
Teresa Carona (Project Manager)
functions, provide the safeguarding of valuable
mouse lines against loss through infection,
disease, or breeding failure, with the possibility
Vivarium
to revitalize the line as needed. These services
facilitate the process of importing / exporting
Nikol Tschaeppe (Manager)
lines and reduce animal suffering. Rederivation is
Rui Costa (Veterinarian)
a generally accepted method for cleaning animals
Joana Almeida (Veterinarian)
from infectious agents. The rederivation process
is extremely important for the transfer of mouse
The Champalimaud Centre for the Unknown
lines produced elsewhere to the specific pathogen
is a multidisciplinary centre for translational
free (SPF) vivarium of the Champalimaud
research in neurosciences and oncology with
Foundation.
complementary facilities supporting biomedical
activities. The vivarium has dedicated areas to
The unit also contains an in-house repository of
rodents - mus musculus andrattus norvegicus,
genetically modified animal lines and offers the
and zebra fish - danio rerio. The facility also
possibility of sharing equipment and know-how
incorporates
enhance
with other institutes with the purpose of promoting
experimental work in a controlled environment.
procedural
areas
to
cooperation and higher profitability of resources
The facility has transgenic & rederivation and
across institutions.
aquatic units offering specialized services. These
areas will continue to evolve on a needs basis.
In addition to the services provided, the unit
Operational procedures are being established to
strives to stay at the forefront of new technologies
ensure the requirements of animal welfare and
and the development of new tools.
best practices of animal husbandry to promote
completive scientific research.
54/55
Aquatic Unit
of the general CCU Drosophila infrastructure,
currently serving a total of 19 researchers from
Ana Certal, PhD (Unit Manager)
three different laboratories (Chiappe, Ribeiro
and Vasconcelos). The CCU Fly Unit also offers
The primary function of the Aquatics Unit is to
services for external institutions and is currently
house, breed and maintain wild-type, mutant and
responsible for the weekly production of fly media
transgenic fish in accordance with the rigorous
for 10 external labs from 3 different institutes:
international
IGC, CEDOC and ITQB.
health
and
welfare
standards
essential for cancer, neuroscience and biomedical
research. The unit also provides state-of-the-art
research support services including educational
support, as advanced courses and workshops
Glass Wash and Media Preparation
Platform
dedicated to the fish as a research model are held
in the unit regularly.
Maria Vito (Platform Manager)
The main fish species housed in the Aquatics Unit
Glass wash and media preparation are core
is Zebrafish, which emerged in the last decade
functions, essential in any research institution.
as one of the key vertebrate model in biomedical,
The Glass Wash & Media Preparation Platform
developmental and behavioral studies. Zebrafish
supports investigators and laboratories at the
are particularly valuable research tools because
Champalimaud Center for the Unknown (CCU)
they develop rapidly, have transparent bodies
by providing cleaning and sterilizing services to
and can be easily manipulated genetically and
lab-ware such as glass and plastic instruments
used for large-scale genetic screens. Their organ
and by preparing high quality tissue culture
systems are very similar to those of humans,
and bacteriological media required for standard
thus zebrafish mutants and transgenics provide
research protocols.
excellent models of human disease.
Fly Facility
Gene Expression Platform
Tânia Vinagre, PhD (Platform Manager)
Isabel Campos, PhD (Unit Manager)
Liliana Costa (Research Technician)
The Gene Expression Platform (GeneX) is an
innovative concept of a scientific and technological
The core purpose of the CCU Fly Unit is to
platform aimed at providing the investigators
provide state of the art conditions for breeding,
of the CNP state-of-the-art molecular biology
maintenance and manipulation of the fly Droso-
expertise, services and equipment.
phila Melanogaster. The equipment of the Fly Unit
includes temperature and humidity controlled
The GenEx Platform offers a variety of technical
chambers for Drosophila breeding and behavioral
services ranging from assuring the safe use and
experiments, CO2 anesthesia stations, scopes for
proper maintenance of shared equipment to the
basic and detailed manipulation and a kitchen
production – including design, synthesis and
dedicated for fly food production. The unit has a
expression optimization – of genetic constructs
committed expert staff that 1) supports researchers
for a number of experimental applications and
in establishing, applying and developing advanced
expression systems.
genetic methods; 2) is deeply involved in training
activities; and 3) assures the proper functioning
Histology Platform
Scientific Software Platform
Ana Santos (Platform Manager)
José Cruz, PhD (Platform Manager)
Leo Madruga (Research Technician)
Ricardo Ribeiro (Software Developer)
In the Histology Platform, researchers work with
The goal of the Scientific Software and Deve-
highly trained staff members who share their
lopment Platform is to provide high-quality
expertise and provide support and services both in
software support, while controlling costs and
experi-mental design and procedures, according to
reducing redundant effort. The platform provides
the researchers’ final objectives.
three classes of service: (1) research, provisioning
and support for existing software; (2) custom
In the Histology Platform, biological samples
development by contract for individuals and groups;
originating from a range of animal models
(3) organization-wide software and research
are processed and analyzed with the use of
support technology. The Platform provides a
sectioning equipment and histochemical and
professional level of service, development and
immunohistochemical techniques. These proces-
support with the aim of reducing redundant effort,
sed samples are then analyzed in the Optical
increasing reusability of software solutions,
Imaging and Microscopy Platform where different
controlling costs and improving the ability of
structures,
investigators to focus on research questions.
cells
and
microorganisms
are
identified.
The Platform could both utilize PhD students
in computer science and engineering as well as
Scientific Hardware Platform
contract any extra development services capacity
to external clients to reduce costs and integrate
the CF with the larger scientific community.
Matthieu Pasquet (Platform Manager)
The goal of the Scientific Hardware Development
Vector Production Platform
Platform is to design electronic hardware that
supports and facilitates research at the CNP. This
Tatiana Vassilevskaia. PhD (Platform Manager)
is an essential service that promotes progress in
research on the individual, group and program
The main goal of the Vector Production (VP)
level.
Platform is to provide research grade viral vectors
to CNP members. Current focus is placed upon:
The platform provides several classes of service
that include general mechanics and electronics
– Virus production and characterization.
consulting and assistance, electronic hardware
Since September 2011, 15 different AAV batches
project development and the use of electronic
have been produced upon requests of CNP
equipment at various support levels. In addition,
investigators. Every purified virus batch has
the hardware platform works in close contact with
been designed in order to meet the requirements
the scientific software development platform. This
of each individual researcher, and characterized
collaboration enables complex project development
by determination of the virus titer (Genome copies
that encompasses electronic hardware, software
per ml, GC/ml) using qRT PCR.
(computer or embedded) and mechanic elements,
providing researchers with specialized, custom
– Management of the common CNP virus repository.
made devices.
The CNP virus registry contains 66 AAV lots, which
were either acquired from outside sources by CNP
56/57
groups (41), or produced by the VP platform (25).
European Union Grant
The data are currently being introduced to the
Female receptivity
more functional Vector Database, created by the
2009-2013
Software platform on request of the VP platform.
Awarded to Maria Luisa Vasconcelos
Future
plans
of
the
VP
Platform
include
optimization of the quality/cost ratio for AAV
European Commission, Food, Agriculture and
production,
Fisheries, and Biotechnology. Project: Copewell
development
of
protocols
for
manipulation, production, and amplification of
A new integrative framework for the study of
different neurotropic viral vectors including
fish welfare based on the concepts of allostasis,
Herpes simplex type1 virus, CAV-2 and others.
appraisal and coping styles
2011-2015
Awarded to Rui Oliveira
Marie Curie Intra-European Fellowship for Career
RESEARCH FUNDING
Development
2011-2015
European Commission
European Union
Awarded to Michael Orger
Marie Curie Intra-European Fellowship
ERC
Advanced
Grant,
European
Research
or Career Development
Council
2010-2012
Optogenetic Analysis of Serotonin Function in the
Awarded to Magor Lorincz
Mammalian Brain
2010-2015
Marie Curie Intra-European Fellowship
Awarded to Zachary Mainen
for Career Development
2009-2011
ERC Starting Grant, European Research Council
Awarded to Léa Zinck
Neural mechanisms of action learning and action
selection: from intentto habit
2009-2014
Fundação Bial
Awarded to Rui Costa
Portugal
Marie Curie International Reintegration Grant
Bial Science Research Grant
Neural mechanisms of action learning
Dopaminergic regulation of dietary learning in
in mouse models
humans and rodents
2009-2013
2011-2014
Marie Curie International Reintegration Grant
Neural mechanisms underlying mate preference
and selection in mice
2009-2013
Awarded to Susana Lima
Bial Research Bursary Grant
Research Project Grant
Investigating the function of synaptic competition
Alternative reproductive tactics in teleost fish: the
in memory formation and mental retardation
peacock blenny (Salaria pavo) as a study model
2011-2014
2008-2011
Awarded to Inbal Israely
Awarded to Rui F Oliveira
Neuronal mechanisms underlying sex hormone-
Neuroendocrine control of reproductive behavior
dependent switching of sexual receptivity
in the Mozambique tilapia: mechanisms and
2011-2013
effects of the social environment
Awarded to Susana Lima
2008-2011
Awarded to Rui F Oliveira
Neural Mechanisms of Social transmission of fear
Postdoctoral Fellowship
2011-2014
2010-2013
Awarded to Marta Moita
Awarded to Hope Johnson
Elucidating the molecular mechanisms mediating
2010-2013
feeding behavior
Awarded to Masayoshi Murakami
2011-2013
Awarded to Carlos Ribeiro
2008-2012
Fundação para a Ciência
e a Tecnologia (FCT)
Portugal
Awarded to Cristina Afonso
2011-2013
Awarded to Fatuel Tecuapelta
Dissecção das bases moleculares e dos circuitos
Investigation Fellowship
envolvidos na intenção
2011
2011-2014
Awarded to João Afonso
2011
Unraveling the Neuronal Circuits Underlying
Awarded to Silvana Araújo
Female Receptivity
2010-2013
Awarded to Maria Luísa Vasconcelos
2011
Awarded to Joaquim Jacob
From genes to behaviour: dissecting the basis for
CO2 response across Drosophilids
2011
2010-2013
Awarded to Ricardo Silva
Awarded to Maria Luísa Vasconcelos
58/59
PhD Fellowship
2011
2011-2015
Awarded to Jens Bierfeld
Awarded to Patrícia Rachinas-Lopes
PhD Fellowship
2011
2010-2014
Awarded to Jacques Bourg
Awarded to Niccolò Bonacchi
PhD Fellowship
2011
2010-2014
Awarded to Roberto Medina
Awarded to Andreia Cruz
PhD Fellowship
2011
2010-2014
Awarded to André Luzardo
Awarded to Elizabeth Rickenbacher
PhD Fellowship
2011
2010-2014
Awarded to Sofia Soares
Awarded to Thiago Gouvêa
PhD Fellowship
2011
2010-2014
Awarded to Luís Moreira
Awarded to Ali Argunsah
PhD Fellowship
PhD Fellowship
2011-2015
2010-2014
Awarded to Gonçalo Lopes
Awarded to Anna Hobbiss
PhD Fellowship
PhD Fellowship
2011-2015
2010-2014
Awarded to Gustavo Mello
Awarded to Sevinç Mutlu
PhD Fellowship
PhD Fellowship
2011-2015
2010-2014
Awarded to Simone Lackner
Awarded to Susana Valente
PhD Fellowship
PhD Fellowship
2011-2015
2010-2014
Awarded to Tiago Marques
Awarded to Ana Machado
PhD Fellowship
PhD Fellowship
2011-2015
2010-2014
Awarded to Raimundo Leong
Awarded to Verónica Corrales
PhD Fellowship
PhD Fellowship
2009-2013
2008-2012
Awarded to Ana Rita Fonseca
Awarded to Rui Azevedo
PhD Fellowship
PhD Fellowship
2009-2013
2007-2011
Awarded to André Mendonça
Awarded to Gil Costa
PhD Fellowship
2009-2013
Awarded to Ana Pereira
PhD Fellowship
2009-2013
Awarded to Scott Rennie
PhD Fellowship
2009-2013
Awarded to Fernando Santos
PhD Fellowship
2009-2013
Awarded to Ana Mafalda Vicente
PhD Fellowship
2009-2013
Awarded to Dennis Herrmann
PhD Fellowship
2009-2013
International Human Frontier Science Program Organization (HFSPO) International
Human Frontier Science Program
Olfactory
objects
and
decisions:
2010-2013
Awarded to Zachary Mainen, Alex Pouget and
Matthieu Luis.
HFSP Long Term Fellowship
Serotonergic modulation of olfactory information
processing
2011-2014
Awarded to Eran Lottem
HFSP Long Term Fellowship
Cell-type specific features of identified serotonergic neurons in the raphe nucle in behaving rats
2011-2014
Awarded to Magor Lorincz
Awarded to João Marques
PhD Fellowship
2008-2012
Uehara Memorial Foundation
Japan
Awarded to Patrícia Correia
Research Fellowship
PhD Fellowship
Awarded to Kensaku Nomoto
2011
2008-2012
Awarded to Maria Inês Vicente
PhD Fellowship
Wellcome Trust
UK
2008-2012
Awarded to Sara Matias
The neural basis of goal-directed behaviour
2011-2015
PhD Fellowship
2008-2012
Awarded to Pedro Ferreira
From
psychophysics to neural computation
Awarded to Thomas Akam
60/61
PUBLICATIONS
Peer-Reviewed Research Articles
Govindarajan, A.*, Israely, I.*, Huang, S.Y.,
Tonegawa,
S.
(2011)
The
dendritic
branch
Bianco IH, Kampff AR, Engert F. (2011)
is the preferred integrative unit for protein
“Prey capture behavior evoked by simple visual
synthesis-dependent LTP. Neuron. 69:132-146.
stimuli in larval zebrafish.” Front Sys Neurosci.
(*authors contributed equally).
2011; 5:101.
Guimarãis M, Gregório A, Cruz A, Guyon N, Moita
Carey MR, Myoga MH, McDaniels KR, Marsicano
MA.Time determines the neural circuit underlying
G, Lutz B, Mackie K, Regehr WG. (2011)
associative fear learning. Front Behav Neurosci.
Presynaptic CB1 receptors regulate synaptic
2011;5:89. Epub 2011 Dec 27.
plasticity at cerebellar parallel fiber synapses.
J Neurophysiol 105, 958-63.
Harris KD, Bartho P, Chadderton P, Curto C, de la
Rocha J, Hollender L, Itskov V, Luczak A, Marguet
Fatima T. Husain, Roberto E. Medina, Caroline
SL, Renart A, Sakata S. (2011) How do neurons
W. Davis, Yvonne Szymbko-Bennett, Kristina
work together? Lessons from auditory cortex.
Simonyan, Nathan M. Pajor, Barry Horwitz (2011).
Hear Res. 271(1-2):37-53.
Neuroanatomical changes due to hearing loss and
chronic tinnitus: A combined VBM and DTI study.
Hooks B. M. , Hires S. A. , Zhang Y., Huber D.
Brain Res. 1369 :74-88.
Petreanu , L., Svoboda K. and Shepherd G. M. G.
Laminar Analysis of Excitatory Local Circuits in
Favaro PD, Gouvêa TS, de Oliveira SR, Vautrelle
Vibrissal Motor and Sensory Cortical Areas. PLoS
N, Redgrave P, Comoli E. (2011). The influence
Biol. 2011 January; 9(1).
of
rat
vibrissal
superior
somatosensory
processing
colliculus
prey
on
in
capture.
Neurosci. 176 :318-27.
Hughes SW, Lörincz ML, Blethyn K, Kékesi KA,
Juhász G, Turmaine M, Parnavelas JG, Crunelli
V (2011). Thalamic Gap Junctions Control Local
Figueira JR, Almeida-Dias J, Matias S, Roy B,
Neuronal Synchrony and Influence Macroscopic
Carvalho MJ, Plancha CE (2011). Electre Tri-C,
Oscillation Amplitude during EEG Alpha Rhythms.
a multiple criteria decision aiding sorting model
Front Psychol 2 :1-11.
applied to assisted reproduction. Int J of Med
Inform 80 (4):262-73.
Itskov PM, Vinnik E, Diamond ME. (2011).
Hippocampal
representation
of
touch-guided
French CA, Jin X, Campbell TG, Gerfen E,
behavior in rats: persistent and independent
Groszer M, Fisher SE, Costa RM (2011). An
traces
Aetiological Foxp2 Mutation Causes Aberrant
PLoS One. 6 (1):e16462.
of
stimulus
and
reward
location.
Activity and Synchrony of Striatal Circuits.
Mol Psychiatry. doi: 10.1038/mp.2011.105.
Lottem E, Azouz R. (2011). A unifying framework
underlying
Geiger JA*, Carvalho L*, Campos I, Santos AC and
the
Jacinto A (2011). Hole-in-one mutant phenotypes
(23):8520-8532.
link EGFR/ERK signaling to epithelial tissue
repair in Drosophila. PLoS One 6 (11):e28349.
(*authors contributed equally).
somatosensory
mecha-notransduction
system.J
Neurosci
in
31
Luan, J.B.; Li, J.M.; Varela, N.; Wang, Y.L.; Li, F.F.;
Special Conference Publications
Bao, Y.Y.; Zhang, C.X.; Liu, S.S.; Wang, X.W (2011).
Global analysis of the transcriptional response of
Brendel W, Romo R, Machens CK (2011). Demixed
whitefly to Tomato yellow leaf curl China virus
Principal Component Analysis. Advances in
reveals their relationship of coevolved adaptations.
Neural Information Processing Systems 24.
J Virol :3330-3340.
Mao T, Kusefoglu D, Hooks BM, Huber D,
Review Articles
Petreanu L, Svoboda K.Long-range neuronal
circuits underlying the interaction between
Carey MR. (2011)
sensory
sensorimotor learning in the cerebellum. Curr
and
motor
cortex.
Neuron.
2011
Synaptic mechanisms of
Oct 6;72(1):111-23.
Opin Neurobiol 21, 609-15.
Soares MC, Oliveira RF, Ros AF, Grutter AS,
Costa, RM (2011). A selectionist account of de novo
Bshary R (2011). Tactile stimulation lowers stress
action learning. Curr Opin Neurobiol. 21(4):579-
in fish. Nat Commun. 2:534.
86.
Varela, N.; Avilla, J.; Anton, S.; Gemeno, C (2011).
Hughes SW, Lorincz ML, Parri HR, Crunelli
Synergism of pheromone and host plant volatile
V (2011). Infraslow (<0.1 Hz) oscillations in
blends in the attraction of Grapholita molesta
thalamic relay nuclei basic mechanisms and
males. Entomologia Experimentalis et Applicata
significance
141 (2):114-122.
Prog Brain Res 193 :145-62.
Varela, N.; Avilla, J.; Gemeno, C.; Anton, S
(2011). Ordinary glomeruli in the antennal lobes
to
health
and
disease
states.
Comments
of male and female tortricid moth Grapholita
Tortricidae)
Santos, FJ, Costa, RM, Tecuapetla, F. (2011).
process pheromone and host-plant volatiles.
Stimulation on demand: closing the loop on deep
J Exp Biol. 214 :637-645.
brain stimulation. Neuron. 72(2):197-8.
Vilas-Boas, F., Fior, R., Swedlow, J.D., Storey, K.G.,
Vicente MI, Mainen ZF (2011). Convergence in the
Henrique, D. (2011). A novel Reporter of Notch
piriform cortex. Neuron. 70 (1):1.
molesta
(Busck)
(Lepidoptera:
Signalling indicates regulated and random Notch
Activation during Vertebrate Neurogenesis. BMC
Biol. 9:58.
Vinnik E, Itskov PM, Balaban E. (2011). Individual
differences in sound-in-noise perception are
related to the strength of short-latency neural
responses to noise. PLoS One. 6 (2):e17266.
Weber F, Machens CK, Borst A (2012). Disentangling
the functional connectivity between optic-flow
processing neurons. Nature Neurosci. 15:441-448.
62/63
SEMINARS AND MEETING ORGANIZED AT THE CNP
Champalimaud Neuroscience
Symposium
21-24 September, 2011
Organizers:
Megan Carey
Marta Moita
Zachary Mainen.
Sponsors:
Blackrock Microsystems, Aralab, Merck Millipore,
TSE Systems, Leica Microsystems, Tecniplast,
Clever
Sys,
Fisher
Scientific,
Bayer,
Lilico
Biotechnology, Ultragene.
The Champalimaud Neuroscience Symposium
brought together 415 researchers from around
the world. The program included 30 distinguished
speakers and two poster sessions. The invited
speakers were chosen to reflect the broad
interests of the Champalimaud Neuroscience
Programme, and covered a broad range of areas
Judith Hirsch, University of Southern California
within neuroscience.
Inhibitory
circuits
for
visual
processing
in thalamus
List of Speakers:
Antonio
Damasio,
Hollis T. Cline, The Scripps Research Institute
University
of
Southern
The
balance
of
inhibition
to
visual
responses
and
excitation
California
regulates
Feeling and sentience: Taking stock
in vivo
Haim Sompolinsky, Hebrew University
Sten Grillner, Karolinska Institute
Neural codes: The curses and blessings of high
The computational logics of networks in
dimensions
motion - from ion channels to behaviour
Gyorgy Buzsaki, Rutgers University
Silvia Arber, Biozentrum and Friedrich Miescher
Neural syntax: segmentation of information in
Institute
the hippocampus
Organizational
principles
of
behavior
antagonistic
motor circuits
Hannah Monyer, Heidelberg University
GABAergic interneurons and their role in
Tom Jessell, Howard Hughes Medical Institute,
neuronal
Columbia University
memory
synchronization,
learning
and
Motor circuits and the sense of place
Detlev Arendt, European Molecular Biology
Alcino J. Silva, University of California, Los
Laboratory
Angeles
Duplication and divergence of neural circuits
Molecular and cellular mechanisms of memory
in bilaterian brain evolution
allocation in neuronal networks
Michael Dickinson, University of Washington
Carla J. Shatz, Stanford University
Visual navigation in Drosophila
Releasing the brake on synaptic plasticity
Daniel Wolpert, University of Cambridge
Larry Abbott, Columbia University
Probabilistic models of human sensorimotor
Functional consequences of different forms of
control
spike-timing dependent plasticity
Leslie B. Vosshall, The Rockefeller University
Human
sweat
and
insect
repellents:
Atsushi Miyawaki, RIKEN Brain Science Institute
the
New fluorescent probes and new perspectives
molecular biology of mosquito olfaction
in bioscience
Ulrike Heberlein, University of California, San
Michael Hausser, University College London
Francisco
Dendritic computation
Social experiences affect ethanol intake in
Drosophila through Neuropeptide F
Carl Petersen, École Polytechnique Fédérale de
Lausanne
Lisa Stowers, The Scripps Research Institute
Specialized
odors
that
generate
Synaptic mechanisms of sensory perception
innate
behavior
Tobias
Bonhoeffer,
Max-Planck-Institute
of
Neurobiology
Takao Hensch, Harvard University
How activity changes synapses in the mam-
Loss of cross-modal cortical activity by vision
malian brain
Yang Dan, University of California, Berkeley
Dissection of neocortical microcircuit
CNP Seminars 2011
James J. DiCarlo, Massachusetts Institute of
January 2011
Technology
Noam Sobel
What neuronal algorithms underlie visual
Thu 13/01/2011
object recognition?
Department of Neurobiology, Weizmann Institute
of Science, Israel
Michael N. Shadlen, University of Washington
Predicting
Medical School
activity from odorant structure
odor
perception
and
neural
Believing and time: a neural mechanism for
February 2011
decision making
Steve Kushner
Kelsey Martin, University of California, Los
Thu 10/02/2011
Angeles
Department of Psychiatry, University Medical
Synapse to nuclear transport of a trans-
Center Rotterdam , Rotterdam, The Netherlands
criptional
Selection of neuronal ensembles during fear
plasticity
regulator
during
neuronal
learning
64/65
March 2011
Regina Sullivan
Jose Carmena
Wed 25/05/2011
Thu 17/03/2011
Emotional
Helen Wills Neuroscience Institute, and Dept.
Institute and New York University School of
of Electrical Engineering & Computer Sciences,
Medicine, US
University of California, Berkeley, USA
Neurobiology of infant attachment: Lessons
Neural adaptations to a brain-machine
from an animal model
Brain
Institute,
Nathan
Kline
interface
June 2011
April 2011
Ingo Willuhn
Mark E Walton
Thu 02/06/2011
Thu 14/04/2011
Departments
Department
of
Experimental
Psychology,
of
Psychiatry
&
Behavioral
Sciences and Pharmacology, University of
University of Oxford, UK
Washington, USA
Is it really worth it? Cost-benefit analyses within
Progression of phasic dopamine signaling
fronto-striatal-monoaminergic circuits
in limbic and sensorimotor regions of the
striatum in a rodent model of drug addiction
Gilles Laurent
Thu 28/04/2011
Tiago Monteiro
Max Planck Institute for Brain Research,
Fri 03/06/2011
Frankfurt, Germany
The Behavioural Ecology Research Group,
Adaptive regulation of activity in an olfactory
University of Oxford, UK
system
Three different approaches to the study of
decision-making, and their implementation
May 2011
in the European starling
Paul Glimcher
Thu 05/05/2011
Hanan Shteingart
Center for Neural Science, New York University,
Mon 06/06/2011
USA
Loewenstein Lab, The Hebrew University of
The Neuroeconomic Analysis of Decision-
Jerusalem, Israel
Making: The Emerging ‘Standard Model’
Primacy in operant conditioning
Jane Hurst
Edward Kravitz
Thu 12/05/2011
Thu 09/06/2011
Institute of Integrative Biology, University of
George Packer Berry Professor of Neurobiology,
Liverpool, UK
Harvard Medical School
A walk on the wild side: what can we learn
Genetic manipulations in the fruit fly fight club:
about scent communication from studies of
love and war in a single gene and other stories
wild mice?
July 2011
Peter Mandik
Yonatan Loewenstein
Thu 19/05/2011
Thu 07/07/2011
Department of Philosophy, William Paterson
Department of Neurobiology, The Hebrew
University, Wayne, US
University, Israel
Does the neuroscience of consciousness need
The computational principles and neural
to care about qualia?
mechanisms underlying choice preference
August 2011
Edward Boyden
Artemy Kolchinsky
Thu 27/10/2011
Fri 05/08/2011
Synthetic Neurobiology Group, MIT, USA
Center for Complex Networks and Systems,
Optogenetics, And Other Neural Circuit
Indiana University, USA
Analysis Tools
(I) Prediction and Modularity in Dynamical
Systems (II) Spatial organization of EEG
November 2011
cross-frequency coupling in a perceptual
Thomas Knopfel
task
Thu 03/11/2011
RIKEN Brain Science Institute, Japan
September 2011
Enhanced genetically-encoded probes for
Tim Behrens
voltage imaging
Thu 01/09/2011
University of Oxford , UK
Ventromedial
Julia Sliwa
prefrontal
cortex
and
Fri 04/11/2011
orbitofrontal cortex contributions to reward
CNRS, Centre de Neuroscience Cognitive - Lyon,
guided behaviour
France
Rhesus monkeys’ behavioral and neuronal
Nicola Clayton
responses to voices and faces of known
Fri 02/09/2011
individuals
University of Cambridge, UK
The Evolution of Shopping Lists
Deborah Gordon
Wed 23/11/2011
Andreas Schaefer
Department of Biology, Stanford University,
Thu 08/09/2011
USA
Max Planck Institute for Medical Research,
The regulation of foraging activity in
Heidelberg, Germany
harvester ants
Mechanisms
Inhibition
of
and
sensory
odour
processing:
discrimination
December 2011
Terry Sejnowski
in mice
Wed 07/12/2011
Frédéric Levy
Computational Neurobiology Laboratory, Salk
Thu 29/09/2011
Lake Institute, USA
Division Animal Physiology and Livestock
Suspicious Coincidences in the Brain
Systems, PHASE, France
Brain mechanisms involved in maternal
motivation and recognition of the young in
sheep
October 2011
James Goodson
Tue 11/10/2011
Center for the Integrative Study of the Animal
Behavior, Indiana University, USA
Neuroendocrine
Diversity in Birds
Mechanisms
of
Social
66/67
INVITED PRESENTATIONS AT INTERNATIONAL MEETINGS
AND INSTITUTIONS
•Development of Brain and Mind Symposium,
Megan Carey
Kobe, Japan
•Lisbon Area Neuroscience Meeting
2011
Endocannabinoid regulation of synaptic
plasticity in the cerebellum
•Keynote, Portuguese Society for Educational
23-Mar-2011. Instituto de Medicina Molecular,
Sciences, Guarda, Portugal
Lisbon, Portugal.
2011
•Society for Portuguese Neuroscience Meeting
The role of endocannabinoids in cerebellar
•ISPA, Lisbon, Portugal
2011
plasticity and learning
27-May-2011. Instituto de Medicina Molecular,
Lisbon, Portugal.
•IMP, Vienna, Austria
2011
•Early Career Scientist Symposium
•100th
Anniversary
The cerebellar circuit: from synapse to
Portugal
behavior
2011
University
of
Lisbon,
7-Nov-2011. Howard Hughes Medical Institute
•College de France, Paris, France
International, Ashburn, VA, USA
2011
Rui M. Costa
•Session
chair,
•CSHL, Cold Spring Harbor, USA
Portuguese
Society
for
2011
Neuroscience Meeting, Lisbon, Portugal
2011
•103rd Titisee Conference, Titisee, Germany
2011
•First Songbird Satellite Symposium, Washington,
USA
2011
•CRG, Barcelona, Spain
2011
•Janelia Conference ‘The Neural Basis of Motor
Control’, Ashburn, USA
2011
•Janelia Farm Research Campus, Ashburn, USA
2011
•FMI, Basel, Switzerland
2011
Inbal Israely
•Cold Spring Harbor Laboratory Meeting
The dendritic branch as an integrative unit
•CRG, Barcelona, Spain
2011
for protein synthesis dependent synaptic
plasticity.
Synapse:
From
Circuits & Behavior.
•Riken BSI, Barcelona, Wako, Japan
2011
13-Apr-2011. CSHL, NY, USA.
Molecules
to
Christian Machens
Marta Moita
•Disentangling the functional connectivity
•Producing and Perceiving Complex Acoustic
between optic-flow processing neurons
Signals: Songbirds and Mice as Model Systems
Jan-2011. University Tubingen, Germany.
Conference
20-23- Mar- 2011. Janelia Farm, USA.
•Workshop on bioinformatics
Information theory in the neurosciences
•103rd
Feb-2011. Humboldt-University Berlin, Germany.
International
Titisee
Conference
on
“Genetic analysis of neural circuits”
23-27-Mar-2011. Titisee, Germany.
•Dynamics
of
an
oculomotor
integrator
revealed by instantaneous optogenetic per-
•“Cutting edge in synapse research”
8-9-Dec-2011. NAIST, Japan.
turbations Jun-2011. Institute for Molecular Pathology,
•15-Dec-2011. RIKEN Brain Science Institute,
Vienna, Austria.
Japan
Zachary Mainen
•Task-dependent
•4-Jan-2011. Tokyo University, Japan.
strategies
for
decision-
making under uncertainty
3-Apr-2011. Columbia University, New York,
Joseph Paton
•A representation of time for learning in the
USA.
striatum of behaving rats
2011. Paris, France.
•Société des Neurosciences 10e Colloque
Neural circuits for odor-guided decisions in
•Parallel distributed processing
the rat
A representation of time for reinforcement
26-May-2011. Marseille, France.
learning in the striatum of behaving rats
•Causal Neuroscience, FENS-IBRO-SfN School
2011. Princeton, NJ, USA.
Targeting the serotonin system using optogenetics: Towards a post-pharmacological
•Decision making in neural circuits
view
A representation of time for learning in the
19-Jun-2011. Bertinoro, Italy.
2011. Ashburn, VA, USA.
•What Makes Us Human?, 2011 GABBA Annual
•A representation of time for learning in the
Symposium
Knowing
what
you
know:Models
and
mechanisms for judgments of confidence
2011. MIT, Boston, MA, USA.
8-Jul-2011. Porto, Portugal.
•“Genes, circuits, behavior” Symposium, RIKEN
Brain Science Institute
Leoplodo Petreanu
•The structure and function of long-range
Neural mechanisms for decision making in
cortical connections the rat: Uncertainty in brain and behavior
30-Nov-2011. Oxford University
21-Oct-2011. Tokyo, Japan
68/69
•The structure and function of sensorimotor
•The Molecular and Neuronal Control of
circuits
Nutrient Choice in Drosophila
2-Dec-2011. Cardiff University, UK.
1-December-2011.
Deprtment
of
Zoology,
Cambridge University, Cambridge, UK.
Carlos Ribeiro
•The neuronal basis of nutrient choices
1-April-2011. Champalimaud Center for the
•Search for neuronal circuits of innate
Unknwon, Lisbon, Portugal
responses in the fruit fly
Oct-2011. National Intitute of Medical Research,
•The Molecular and Neuronal Control of
London, UK.
26-April-2011. ICVS, University of Minho, Braga,
Portugal.
Wieland Brendel
•Multi-electrode workshop
•The neuronal basis of nutrient choices
Demixed Principal Component Analysis
Oct-2011. INSERM, Lyon, France.
10-May-2011. IGC, Portugal.
•XII Meeting of the Portuguese Society for
Neuroscience
The Molecular and Neuronal Control of
Ricardo Benjamim Leitão
Gonçalves
•Metabolism and nutritional decision, present
and future of a model
27-May-2011. Lisbon, Portugal.
16-November-2011. ISAVE (Instituto Superior de
•The Molecular and Neuronal Control of Nutrient
Choice in Drosophila 22-June-2011. Instituto de Medicina Molecular,
University of Lisbon, Lisbon, Portugal.
•E3 forum, Education, Employment, Entrpreneurship, MIT Portugal Program
Where did I go and how did I get there?
30-June-2011. Lisbon, Portugal.
•The
first
Junior
European
Drosophila
Investigator meeting
The Behavior and metabolism laboratory
2-September-2011. Leysin, Switzerland.
•22nd European Drosophila Research Conference
The Molecular and Neuronal Control of
22-September-2011. Lisbon, Portugal.
Saúde do Alto Ave), Póvoa de Lanhoso, Portugal.
GRADUATE TRAINING AND EDUCATION
International Neuroscience
Doctoral Programme (INDP)
•Jacques Bourg
BS, Electrical Engineering
INSA de Lyon , Institut National des Sciences
Programme Director
Appliquées de Lyon, France
Zachary Mainen
•Jens Bierfeld Programme Coordinator
Master in Biology
Alfonso Renart
University of Konstanz, Konstanz, Germany
Administrative Assistant
•João Afonso Alexandra Piedade
Master in Clinical Psychology
Instituto Superior de Psicologia Aplicada,
The INDP aims at providing students with a
Lisboa, Portugal
broad and integrative education in neuroscience
with a focus on the neuronal and circuit basis
•Joaquim Jacob
of behavior. A main goal of the program is
Master in Neuroscience
to foster and encourage active participation,
Faculty of Medicine of the University of Lisbon,
independence and critical thinking on the part
Lisbon, Portugal
of the students. The first year of the program,
students attend courses structured as modules
•Ricardo Zacarias
lasting one or a few weeks which cover basic
Master in Evolutionary and Developmental Biology
topics in contemporary neuroscience such as
Faculdade de Ciências da Universidade de Lisboa,
basic cellular and synaptic physiology, sensation
Lisbon, Portugal
and action and cognitive neuroscience. Quantitative approaches are emphasized and students
•Roberto Medina
also receive background courses on basic bio-
BA, Mathematics
logy, mathematics and programming. The next
University of Illinois at Urbana-Champaign,
three years are dedicated to research on a
Champaign, USA
specific topic leading to a PhD thesis. No previous background in neuroscience is required,
•Silvana Araújo
but candidates with a background in biology
Master in Psychopharmacology
or
University of Nottingham, Nottingham, United
quantitative
disciplines
are
encouraged
to apply.
INDP Students
Kingdom
•Sofia Soares Master in Human Biology and Environment
Faculty of Science - University of Lisbon, Lisbon,
2011 Students
•André Luzardo
Portugal
•Luis Moreira BA, Psychobiology
Master in Ecology
Universidade de São Paulo, Ribeirao Preto, Brazil
University of Coimbra, Coimbra, Portugal
70/71
2010 Students
2009 Students
•Bruno Miranda
•Ali Ozgur Argunsah
The role of the entorhinal cortex in instru-
Hippocampal synaptic plasticity induced by
mental conditioning Laboratory of Steven
natural spike trains
W. Kennerley, University College of London, UK
Laboratory of I. Israely, CNP
•Ana Carolina de Sousa
•Andreia Cruz
Ant interaction networks: Task allocation in
Lessons from others: a study of the mechanisms
colonies in need of a new nest Laboratory
underlying social learning
of N. Franks, University of Bristol, UK
Laboratory of M. Moita, CNP
•Gustavo Mello
•Anna Hobbiss
Influence of cortical input on time dependent
Clustered plasticity as a model for micro-
striatal activity in rodents during interval
rewiring Laboratory of I. Israely, CNP
timing Laboratory of J. Paton, CNP
•Diogo Peixoto
•Gonçalo Lopes
Dynamics of neural activity in LIP during
Dissecting the Neural Basis of the Insect
decision-making Laboratory of W. Newsome,
Path Integrator: A Comparative Approach
Stanford Univ., USA
Laboratories of J. Paton & A. Kampff, CNP
•Elizabeth Rickenbacher
•Ivo Marcelo
Social modulation of fear extinction
Characterization of memory trace networks in
the lateral amygdala during consolidation
Laboratory of S. Kushner, Erasmus MC: University Medical Center Rotterdam, The Netherlands
•David Raposo
The integration of evidence across modalities
in the brain Laboratory of A. Churchland, Cold
•Raimundo Coelho Leong
Spring Harbor Laboratory, USA
Flexible decision-making in winner-take-all
networks through activity-dependent positive
•Niccolò Bonacchi
feedback
Context dependent modulation of value
Laboratory of A. Renart, CNP
Laboratory of Z. Mainen, CNP
•Tiago Marques
•Pedro Garcia da Silva
A novel paradigm for studying feature-based
Neuromodulatory
attention in the mouse primary visual cortex
representations in the rodent olfactory bulb
using a calcium imaging brain-machine interface
Laboratory of F. Albeanu, Cold Spring Harbor
Laboratory of L. Petreanu, CNP
Laboratory, USA
•Simone Lackner
Understanding
enhancement
of
odor
•Raquel Abreu
the function of Hypocretin/
Somatostatin-expressing
neurons
of
the
Orexin expressing neurons in neural circuits
PreBötzinger Complex underlying Central Sleep
controlling visual-evoked locomotor behavior
Apnea Laboratory of J. Feldman, UCLA, USA
in larval zebrafish
Laboratory of M. Orger, CNP
•Sevinç Mutlu
•Scott Rennie
Cortical dynamics of excitation and inhibition
The neural basis of social decision making,
during passive and active perception
Rodents playing an iterated stag hunt game
•Thiago Gouvêa
•Ana Mafalda Vicente
Motivational state modulation of decision making:
Neural Mechanisms Underlying The Shift
reward expectation, phasic dopamine and choice
Between Goal-Directed and Habitual Actions
accuracy Laboratory of Z. Mainen, CNP
Laboratory of R. Costa, CNP
2008 Students
•Dennis Herrmann
Functional Architecture of the Neural System
•André Mendonça
Controlling
Female
Reproductive
Behavior
Attentional modulation of odor discrimination
in Drosophila melanogaster Laboratory of
in rodents Laboratory of Z. Mainen, CNP
L. Vasconcelos, CNP
•Ana Rita Fonseca
2007 Students
Neural Mechanisms of Action Inhibition and
Generation Laboratory of Z. Mainen, CNP
•Patrício Simões
The Influence of Phase Change on Learning
•Clara Ferreira
and Memory in Desert Locusts Laboratory
The role of octopaminergic neurons in appetitive
of J. Niven, Department of Zoology, University
olfactory learning and memory in Drosophila
of Cambridge, UK
melanogaster Laboratory of G. Miesenböck,
University of Oxford, United Kingdom
•Isabel Henriques
Hydrogen
•Fernando Santos
Neuronal ensemble selection and competition
Sulphide
Mechanisms
in
Acute
Cerebral Ischemia Laboratory of J. Ferro,
Universidade Autónoma de Madrid, Spain
during motor skill learning Laboratory of R.
Costa, CNP
•Rodrigo Abreu
Neuronal and endocrine mechanisms underlying
•João Marques
cognitive appraisal and social modulation of
Understanding the Neural Mechanisms that
behaviour in zebrafish (Danio rerio) Laboratory
Control Speed in Zebrafish Larvae
of R. Oliveira, Instituto Superior de Psicologia
Laboratory of M. Orger, CNP
Aplicada, Portugal
•Ana Pereira
•José Joaquim Fernandes
Sound discrimination in fear conditioning:
Neural correlates of hierarchical learning
an interaction between cortical and thalamic
Laboratory of M. Botvinick, Neuroscience
auditory structures Laboratory of M. Moita, CNP
Institute, Princeton University, USA
•Ana Isabel Amaral
•Íris Vilares
A Bayesian approach to audio-hallucinatory
Uncertainty and decision making in the human
perception using oddball paradigm Laboratory
brain: economics and motor control
of D. Langers, Dep. of Otorhinolaryngology,
Laboratory of K. Koerding, Rehabilitation Insti-
University of Groningen, The Nederlands
tute of Chicago, Northwestern University, USA
72/73
(CNP), Chris Braun (Department of Psychology
•Patrícia Correia
Serotonin function in behavior
Hunter College Biopsychology Program City
University of New York, USA)
Cellular Physiology (24 - 28 January)
•Maria Inês Vicente
Neural mechanisms of uncertainty in brain
Organizers: Joshua Dudman (Howard Hughes
function and behavior
Medical Institute, USA)
Teachers: Alex Reyes (Center for Neural Science
- New York University, USA)
•Pedro Ferreira
Circuit analysis of epigenetic changes during
Circuits (31 January - 4 February)
the consolidation of skills
Organizers: Michael Orger (CNP)
Laboratory of R. Costa, CNP
Teachers:
Ruben
Português
(Department
of Molecular and Cellular Biology, Harvard
University, USA)
•Margarida Agrochão
Towards an ecological approach to vision:
wireless recording from rat V1
Plasticity (7 - 11 February)
Laboratory of M. Meister, Department of
Organizers: Inbal Israeli (CNP)
Molecular Cellular Biology,
Teachers: Steve Kushner (Erasmus MC University
Harvard U. Uni.
Medical Center Rotterdam, The Netherlands)
University, USA
Learning (14 - 18 February)
•Mariana Cardoso
Testing the Role of Cerebral Blood Flow on
Organizers: Megan Carey (CNP)
Neuronal Activity, in Mice Olfactory Glomeruli
Teachers: Sam Sober (School of Biology Emory
Laboratory of A. Das, Department of Neuros-
University Atlanta, USA)
cience, Columbia University, College of Physi-
Metabolism (28 February - 4 March) cians and Surgeons, USA
Organizers: Carlos Ribeiro (CNP)
2011 Individual Courses
Teachers: Matt Piper (University College London,
UK)
Spring Courses in Neuroscience
Held
at
the
Champalimaud
Neuroscience
Program (CNP)
Sensory & Motor (7 - 11 March)
Organizers:
Carlos
Ribeiro
(CNP),
Eugenia
Chiappe (Howard Hughes Medical Institute, USA),
Introduction (10 - 14 January)
Michael Orger (CNP)
Organizers: Susana Lima (CNP), Marta Moita
Teachers: Eugenia Chiappe (Howard Hughes
(CNP), Carlos Ribeiro (CNP)
Medical Institute, USA)
Teachers: Susana Lima (CNP), Marta Moita (CNP),
Carlos Ribeiro(CNP)
Movement into Action (14 - 18 March)
Organizers: Rui M. Costa (CNP)
Introduction: Evolution ( 17 - 21 January)
Teachers: José Carmena (Department of Electrical
Organizers: Susana Lima (CNP), Marta Moita (CNP),
Engineering and Computer Sciences, University
Carlos Ribeiro (CNP), Maria Luísa Vasconcelos
of California, Berkeley, USA), Joe Mcintyre (CNRS
(CNP)
Laboratoire de Physiologie de la Perception et de
Teachers: Susana Lima (CNP), Marta Moita (CNP),
l’Action - College de France, France)
Carlos Ribeiro (CNP), Maria Luísa Vasconcelos
Experimental Approaches- Basic
(21 - 25 March)
Teachers: Regina Sullivan (Department of Zoology, University of Oklahom, USA)
Organizers: Adam Kampff (CNP), Michael Orger
(CNP), Florian Engert (Harvard University)
Extroduction (30 May - 3 June)
Teachers: Adam Kampff (CNP), Michael Orger
Organizers: Élio Sucena (IGC)
(CNP)
Autumn Courses in Integrative Biology
Experimental Techniques–Advanced
(28 March - 1 April)
Held at the Instituto Gulbenkian de Ciência
(IGC)
Organizers: Adam Kampff (CNP), Michael Orger
Teachers: Florin Albeanu (Cold Spring Harbor
History of Biological Concepts
(3 - 7 October)
Laboratory, USA)
Organizers: Thiago Carvalho (IGC)
(CNP), Florian Engert (Harvard University)
Teachers: Pietro Corsi (Faculty of History,
Projects (4 - 15 April) University of Oxford, UK), Jonathan Howard
Organizers: Adam Douglass (Harvard University,
(Department of Cell Genetics, Institute for
USA), Janet Iwasa ( Department of Teachers: Cell
Genetics,
Biology - Harvard Medical School, USA)
Thiago Carvalho (IGC), Chrirsten Mirth (IGC),
University
of
Cologne,
Germany),
Lars Jansen (IGC), José Pereira Leal (IGC), Joe
Computational Approaches (26 - 29 April)
Paton (CNP)
Organizers: Christian Machens (CNP), Alfonso
Teachers: Sophie Deneve (Départment d’Etudes
Molecular and Structural Biology
(10 - 14 October)
Cognitives (DEC) at the Ecole Normale Supérieure),
Organizers: Alekos Athanasiadis (IGC)
John Hertz (Niels Bohr Institute, Denmark)
Teachers: Niels Gehring (Institute for Genetics,
Renart (CNP)
University of Cologne, Germany), Guillermo
Vision to Decision (9 - 13 May)
Montoya (Spanish National Cancer Research
Organizers: Joe Paton (CNP)
Centre, Spain), Manwlis Matzapetakis (Instituto
Teachers:
Hughes
de Tecnologia Química e Biológica, Portugal),
Flanigan
Claudio Soares (Instituto de Tecnologia Química
(Ludwig-Maximilians-Universität - Department
e Biológica, Portugal), Bruno Viktor (Instituto de
of Neurology, Germany), Brian Lau (Dept of
Tecnologia Química e Biológica, Portugal)
Medical
Gabe
Murphy
Institute,
USA)
(Howard
Virginia
Neuroscience Columbia University, USA), Kenway
Louie (Center for Neural Science, New York
Inside the Cell(17 - 21 October)
University, USA) David Freedman (Department of
Organizers: Lars Jansen (IGC)
Neurobiology, The University of Chicago, USA)
Teachers: Niels Gehring (Institute for Genetics,
University
of
Cologne,
Germany),
Bjoern
Consciousness (16 - 20 May)
Schumacher( CECAD Cologne at the Institute
Organizers: Zach Mainen (CNP)
for Genetics, University of Cologne, Germany),
Teachers: Peter Mandik (Department of Philosophy
Geneviève Almouzni (Nuclear Dynamics and
William Paterson University of New Jersey, USA),
Genome Plasticity Unit, Curie Institute, France),
Brian L. Keeley (Pitzer College, USA)
Andrew Holland (Ludwig Institute for Cancer
Research, USA), Rob Wolthuis (The Netherlands
Social Interactions (23 - 27 May)
Organizers: Marta Moita (CNP), Susana Lima (CNP)
Cancer Institute, The Netherlands)
74/75
Cells to Organisms I (24 - 28 October)
Evolution (21 - 25 November)
Organizers: Thiago Carvalho (IGC)
Organizers: Isabel Gordo (IGC)
Teachers: Mathieu Molet (Université Pierre et
Teachers: Brian Charlesworth (School of Biological
Marie Curie, France), Kevin Foster (Department
Sciences, University of Edimburgh, UK), Olivier
of Zoology, Oxford University, UK), Pierre
Tenaillon (Faculté de Médecine Xavier Bichat,
Golstein (Centre d’Immunologie de Marseille-
Universite de Paris VII, France), Michael Turelli
Luminy, France), Etienne Danchin (Directeur
(University of California, Davis, USA), Henrique
de Recherche CNRS Head of the Laboratoire
Teotónio (IGC), Gabriela Gomes (IGC)
Evolution et Diversité Biologique Univ. Paul
Sabatier, France)
Evolution, Development and Ecology (28
November - 2 December)
Cells to Organisms II - Limb Development
(31 October - 4 November)
Organizers: Patricia Beldade (IGC), Élio Sucena
Organizers: Diogo Castro (IGC), Joaquin Léon
Teachers: Atanasios Pavlopoulos (University of
(IGC)
Cambridge, UK), Christian Braendle (Université
Teachers: Malcolm Logan (National Institute for
de Nice, France), Johannes Jaeger (EMBL - center
Medical Research, UK), Juan Hurlé (University
for Genomic Regulation, Spain), Patricia Beldade
of Extremadura, Spain), James Sharpe (EMBL
(IGC), Élio Sucena (IGC), Christen Mirth (IGC)
(IGC), Christen Mirth(IGC)
- Center for Genomic Regulation, Spain), Diogo
Castro (IGC), Joaquin Léon (IGC), Florence Janody
Instrumentation (5 - 10 December)
(IGC), Solveig Thorsteinsdottir (FCUL)
Organizers: Nuno Moreno (IGC)
Teachers: Andrew Riddell (Head of Flow Cytometry
Statistics (7 - 11 November)
Core Facility, EMBL, Germany), Jan Willem Brost
Organizers: Jorge Carneiro (IGC)
(JWB, The Netherlands), Nuno Moreno (IGC),
Teachers: Jorge Carneiro (IGC)
Emilio Gualda (IGC), Gabriel Martins (IGC), Pedro
Almada (IGC), Jorg Becker (IGC), José Rino (IMM)
Genetic Models (14 - 18 November)
Organizers: Vitor Barbosa (IGC)
Neurobiology (12 - 19 December)
Teachers: Jesús Aguirre (Dep. de Biología Celular
Organizers: Michael Orger (CNP), Maria Luísa
y Desarrollo, Inst. de Fisiología Celular, Univ.
Vasconcelos (CNP)
Nacional Autónoma de México, México), Fernando
Teachers: Rui Costa (CNP), Zach Mainen (CNP),
Roch (University of Toulouse, France), Karen
Michael Orger (CNP), Alfonso Renart (CNP),
Liu (King’s College London, UK), Miodrag Grbic
Adam Kampff (CNP), Inbal Israeli (CNP), Carlos
(University of Western Ontario, Canada), Thiago
Ribeiro (CNP), Susana Lima (CNP), Maria Luísa
Carvalho (IGC), Filipa Alves (IGC), Sara Carvalho
Vasconcelos (CNP), Joe Paton (CNP), Magor
(IGC), Ana Borges (IGC), Clara Reis (IGC), Moises
Lorincz (postdoctoral fellow, CNP), Florian A.
Mallo (IGC), Elena Baena (IGC), Ana Mena (IGC)
Dehmelt (PhD student, CNP)
SCIENTIFIC OUTREACH – AR EVENTS
Drawing on the enthusiasm of the Champalimaud
Neuroscience
Programme
community
and
spearheaded by students, a series of science
communication events called Ar was established.
Ar is Portuguese for air, representing how
pervasive and fundamental science is in our daily
lives. The events explore fundamental scientific
themes by intertwining work from leading
thinkers, both ‘in house’, local and international
such as scientists Rui Costa and Ed Boyden and
artist Vik Muniz, through entertaining dynamic
presentations, cutting edge interactive games
further discussion and greater understanding of
and open discussion. Each event has drawn more
key concepts. Supporting these regular events,
than 400 people filling the waterfront auditorium
we have implemented a range of online resources,
of the Champalimaud Foundation by the river
including streaming and hosted multimedia
Tagus in Lisbon, Portugal, and has received
content, a webzine and social networking that
wide acclaim in important local publications.
links the actual events with a range of relevant
Enthusiastic feedback has indicated that the vast
established sources from scholarly blogs to TED
majority of the attendees have actively engaged
talks and much more. Going forward we aim to
with the often complex issues, ranging from
capitalize on our success to continue to build
BMI’s to optogenetics and emergence, leading to
and consolidate webs of interaction with the local
community, sharing knowledge of fundamental
scientific ideas and their underlying process of
thought.
Organizers:
TS Gouvea, BAC Afonso, C Afonso, N Bonacchi, W
Brendel, V. M. Corrales, PA Correia, GMP Costa, FA
Dehmelt , EEJ Dewitt, AR Fonseca, AF Hobbiss,
S Lackner, GC Lopes, TG Marques, SPS Matias,
AG Mendonça, SV Meyler, C Monroy, CEL Ramos,
SM Rennie, SLS Soares, R Venturini, A Vicente, E
Vinnik, AR Kampff, ZF Mainen.
Programa
de Cancro
5. Programa de Cancro
5.1. Programa Doutoral para Médicos
5.2 Simpósios e Reuniões:
5.3. Champalimaud Metastasis Programmes
78/79
Prof. James Watson, Presidente do Conselho Científico da Fundação Champalimaud,
na abertura do Champalimaud Cancer Research Symposium,
em homenagem ao Dr. Judah Folkman
Programa de Cancro
5.1. Programa Doutoral
para Médicos
Em 2011 teve início a 4.ª edição (2011-12) do Programa
de Formação Médica Avançada (PFMA), uma iniciativa
da Fundação Calouste Gulbenkian com a participação
da Fundação Champalimaud.
Para esta quarta edição foram admitidos nove candidatos, todos em full-time, de acordo com a recomendação
do External Advisory Board na avaliação do Programa
feita em Maio de 2010.
O Centro Clínico Champalimaud conta já com a colaboração da Dra. Sofia Braga, especialista de Oncologia
Clínica, e do Dr. Nuno Figueiredo, especialista em Cirurgia, que participaram ambos na 1.ª edição do PFMA.
5.2. Simpósios e Reuniões
Champalimaud Cancer Research Symposium,
em homenagem ao Dr. Judah Folkman
A Fundação Champalimaud acolheu cerca de 15 reputadíssimos especialistas mundiais em investigação oncológica, que participaram nos dias 14 e 15 de Janeiro
num simpósio sobre angiogénese homenageando o
trabalho do Dr. Judah Folkman. Este simpósio foi organizado pelo Presidente do Conselho Científico da Fundação, James Watson, tendo sido aberto pela Presidente
da Fundação, que aproveitou a ocasião para agradecer
a presença dos participantes em Lisboa, mencionando o
impacto do trabalho desenvolvido pelo Dr. Folkman em
prol da investigação oncológica. A Prof.ª Mina Bissell, investigadora e distinta cientista do Lawrence Berkeley National Laboratory, prestou igualmente o seu testemunho
sobre a inspiradora visão de Judah Folkman e todos os
participantes que intervieram como oradores partilharam
desse testemunho ao apresentarem os seus trabalhos
de investigação em angiogénese
Dr. Mina Bissell, Life Sciences Division, Lawrence Berkeley
National Laboratory, Berkeley, CA, EUA
Judah Folkman
A palavra “pioneiro” é nos dias de hoje utilizada com
não podem ser ignorados e existem actualmente mais
alguma frequência e muitas vezes sem grande consis-
de 100 laboratórios, a nível mundial, a desenvolver
tência. Contudo, no caso do Dr. Judah Folkman esta
investigação em angiogénese, e mais de um milhão de
definição pode ser utilizada com toda a justiça: quando ele
pacientes a receberem tratamento anti-angiogénico.
propôs que um tumor poderia ser controlado, cortando
a sua alimentação sanguínea, enfrentou muitas vezes
A Fundação Champalimaud teve igualmente o gosto de
por parte da comunidade científica algum cepticismo
receber nesta ocasião a sua mulher, Paula Folkman, que
e até menosprezo. Apesar disso, ele perseverou nesta
se deslocou a Lisboa para poder estar presente nesta
via, desenvolvendo o seu trabalho com muita convicção
homenagem científica ao marido.
e determinação. Os resultados clínicos do seu trabalho
O programa do Simpósio teve as seguintes
intervenções:
Hellmut Augustin, Vascular Biology, Medical Faculty Mannheim, Heidelberg University (CBTM), and German
Cancer Research Center Heidelberg (DKFZ-ZMBH
Alliance), Germany: VEGF- and Agiopoietin-Mediated
signaling pathways in endothelial cells.
Mina Bissell, Life Sciences Division, Lawrence Berkeley
National Laboratory, Berkeley, CA: The microenvironment and the genome in breast cancer: How does tissue
Paula Folkman e Prof. James Watson
architecture inform therapy?
80/81
Lena Claesson-Welsh, University of Uppsala, Depart-
Yongzhang Luo, National Engineering Laboratory for
ment of Genetics and Pathology, The Rudbeck Labo-
Anti-tumor Protein Therapeutics, Beijing Key Laboratory
ratory, Uppsala, Sweden: Histidine-rich glycoprotein is
for Protein Therapeutics, Cancer Biology Laboratory,
an endogenous regulator of tumor inflammation and anti-
School of Life Sciences, Tsinghua University, Beijing,
-tumor response.
P. R. China: Unraveling the Mysteries of Endostatin: cycles
Elisabetta Dejana, FIRC Institute of Molecular Oncology
of bench to bedside.
and University of Milan, School of Sciences, Milan, Italy:
Donald McDonald, UCSF Comprehensive Cancer
Endothelial cell to cell junctions and Wnt signaling in the
Center, Cardiovascular Research Institute, and Depar-
control of vascular morphogenesis.
tment of Anatomy, University of California, San Francisco,
Napoleone Ferrara, Genentech, Inc., San Francisco, CA,
USA: VEGF-dependent and -independent angiogenesis.
Kairbaan Hodivala-Dilke, The Adhesion and Angiogenesis Laboratory, Centre of Tumour Biology, Institute of
Cancer and Cancer Research UK Clinical Centre, Barts
& The London, Queen Mary’s School of Medicine &
Dentistry, John Vane Science Centre, London, UK: Dose
matters and angiogenesis
San Francisco, CA, USA: Angiogenesis Inhibitors in
Cancer: Paradox or Tumor Biology.
Gregg Semenza, Vascular Program, Institute for Cell
Engineering; McKusick-Nathans Institute of Genetic
Medicine; and Departments of Pediatrics, Medicine,
Oncology, Radiation Oncology, and Biological Chemistry,
The Johns Hopkins University School of Medicine,
Baltimore, MD 21205, USA: Hypoxia-Inducible Factor 1:
Tumor Angiogenesis and More.
Lars Holmgren, Department of Oncology and Patho-
James Watson, Cold Spring Harbor Laboratory, USA:
logy, Karolinska Institutet, Stockholm, Sweden: The
Judah Folkman, Anti-angiogenesis and the Curing of
angiomotin family in control of vascular cell polarity.
Cancer.
Raghu Kalluri, Harvard Medical School, Boston, USA:
Zena Werb, Department of Anatomy, University of
Letters and teachings of Judah Folkman.
California, San Francisco, CA, USA: New insights into
Yibin Kang, Princeton University, Princeton, USA: Stromal
Interactions in Breast Cancer Bone Metastasis.
mechanisms underlying a role for tumor vascular stability
in chemotherapeutic responses.
Mark Kieran, Dana-Farber Cancer Institute, USA: Targeting Endothelial-Derived Epoxyeicosatrienoic Acids (EETs)
mediated Angiogenesis.
Auditório da Fundação Champalimaud
Champalimaud Cancer Research Symposium, em homenagem ao Dr. Judah Folkman,
14 e 15 Janeiro de 2011
5.3.Champalimaud Metastasis Programmes
Yibin Kang
Molecular Mechanism of Breast Cancer
Metastasis
Group members (as of 06/2012)
Yong Wei (Research Associate)
Rumela Chakrabarti (Post-doc)
Hanqiu Zheng (Post-doc)
Toni Celia Terrassa (Post-doc)
Heath Smith (Post-doc)
Brian Ell (PhD Student)
Liling Wan (PhD Student)
Maša Alečković (Ph.D. Student)
Bong Ihn Koh (Ph.D. Student)
Mark Esposito (Ph.D. Student)
Wenyang Li (Ph.D. Student)
Min Yuan (Research Technician)
Xiang Hang (Research Technician)
Our study on the biphasic role of the miR-200 family of
miRNAs in breast cancer metastasis, together with two other
articles on breast cancer research, was highlighted in the
cover of the September 2011 issue of Nature Medicine.
Metastasis, the spread of cancer cells from the
primary tumor to distant organs, is the most
dreadful development of neoplastic diseases.
The mission of our laboratory is to apply modern
In the past year, with the support of the
molecular biology, genomics, and computational
Champalimaud Foundation, we have made several
biology approaches to understand the molecular
major breakthroughs that lead to publication of
basis of cancer metastasis.
Major areas of
several high impact papers in Cancer Cell, Nature
research in our laboratory includes: identification
Medicine, Nature Reviews Cancer, etc. These
and functional characterization of metastasis
studies illustrate a novel role of Notch signaling
genes, pre-clinical evaluation of anti-metastasis
in osteolytic bone metastasis, the dynamic
therapeutics, development of advanced imaging
function of the miR-200 family microarrays in
technology and non-invasive detection of tumor-
breast cancer metastasis, the genetic basis for the
-stroma interaction during metastasis, the role
transition of dormant bone micrometastases to
of miRNA in cancer progression and metastasis,
overt metastasis. The following summarizes our
molecular characterization of mammary gland
major findings in the studies of molecular basis of
stem cells and their link to breast tumor stem
breast cancer progression and metastasis that we
cells.
conducted in the past year.
82/83
Jagged1-Notch signaling in osteolytic bone
metastasis (Cancer Cell, 2011)
metastasis, once again highlighting the aberrant
use of developmentally conserved pathways in
cancer progression.
Although previous work in our lab and others
clearly established the importance of TGFβ
signaling in bone metastasis, it was unclear
which genes among hundreds of TGFβ targets
VCAM1 as a driver for the activation of
dormant bone micrometastases (Cancer
Cell, 2011)
in cancer cells are crucial for driving bone
metastasis. In this study, we identified Jagged1
In breast cancer, metastatic relapse often occurs
as a crucial TGFβ downstream target which
after a prolonged period of clinically disease-
activates Notch signaling in bone stromal
free survival. The constant risk of recurrence is
cells to stimulate osteoclast differentiation
a source of substantial anxiety for breast cancer
and promote tumor growth through the IL-6
survivors and their families. Unfortunately, the
feedback loop. Bone destruction releases TGFβ
effort to understand the molecular basis of
to increase Jagged1 expression in tumor cells,
tumor dormancy and the subsequent metastatic
which in turn promotes osteoclastogenesis and
activation of indolent micrometastases is hindered
further degradation of bone matrix, forming a
by the lack of suitable animal models. This study
previously unknown vicious cycle in osteolytic
reported a functional genomic analysis of a
bone metastasis.
unique mouse model of indolent micrometastases
in bone and their activation to life-threatening
This series of work established the TGFβ , Notch
overt metastases. Using this model, we identified
and IL-6 signaling pathways as key components
VCAM1 as a crucial functional driver of this
in the network of “seed and soil” interaction in
process. We showed that tumor-derived soluble
bone metastasis and validated them as potential
VCAM1 serves as a chemoattractant to recruit
therapeutic targets. Based on this study, we have
circulating monocytic precursors of osteoclasts
developed a humanized neutralizing antibody
to indolent bone micrometastases. By interacting
against Jagged1, which has shown great efficacy
with its cognate receptor α4β1 intergrin, VCAM1
in reducing metastatic tumor growth in bone
also promotes the adhesion of pre-osteoclasts to
and pathological bone destruction, while having
the surface of tumor cells. These events increase
no significant adverse side effects or impact
the local density of pre-osteoclasts to facilitate
on physiological bone remodeling. This line of
their fusion and differentiation into mature
research may eventually lead to the development
bone-degrading osteoclasts, thereby initiating
of a new class of targeted therapeutics for bone
the vicious cycle of osteolytic bone metastasis.
metastasis that may be superior to the currently
VCAM1 is previously known to be important for
available therapeutics such as bisphosphonates
adhesion of leukocytes to endothelial cells during
and RANKL-blocking antibodies.
inflammation. Here, the function is hijacked by
tumor cells to initiate the development of bone
Previous research in Notch signaling has linked
metastasis.
hyperactive tumor-intrinsic Notch signaling to
tumorigenesis in leukemia and some solid tumors.
This study established VCAM1 as a potential
In contrast, this study is one of the first examples
target to prevent metastatic recurrence in high
of how tumor-derived Notch ligands activate
risk breast cancer patients. Indeed, neutralizing
Notch signaling in stromal cells to promote tumor
antibodies against VCAM1 or α4β1 integrin
progression. The findings from this work also
significantly reduced the growth of bone metas-
linked two important developmental pathways
tasis, especially when applied as preventive
(TGFβ and Notch) in the pathogenesis of bone
treatments.
In order to facilitate the analysis of real-time
miR-200s were therefore widely expected to be
interaction dynamics between tumor cells and
suppressors of metastasis.
monocytic precursors of osteoclasts at the single
found that miR-200 overexpression is associated
cell level in the bone marrow, we also developed
with poor distant relapse-free survival of breast
a novel ex vivo multiphoton fluorescent imaging
cancer
technique.
metastatic
This new method represents an
patients
and
Surprisingly, we
functionally
colonization
in
mouse
promotes
models.
important technical contribution to the field by
Supporting this paradoxical finding, we showed
significantly increasing the resolution of imaging
that miR-200 overexpression elicits a global shift
of tumor-stromal interaction in hard tissues.
of gene expression profiling toward that of highly
metastatic cells. Among several novel miR-200
The biphasic role of the miR-200 family in
breast cancer metastasis (Nature Medicine,
2011)
targets identified through an integrated genomic/
proteomic analysis, the Sec23a secretory pathway
stood out as a prominent functional target with
significant functionality in suppressing metastatic
The role of epithelial-mesenchymal transition
colonization. We further identified IGFBP4 and
(EMT) in promoting tumor invasion in the early
TINAGL1 as important Sec23a-dependent secreted
steps of metastasis has been increasingly well
proteins with significant metastasis suppressive
recognized.
However, the pathological and
functions. We are currently developing TINAGL1
clinical importance of the reverse process,
fragments for potential therapeutic application in
mesenchymal-epithelial transition (MET) is still
preventing lung metastasis.
poorly understood.
This study was one of the
most extensive analyses of MET in experimental
Beyond revealing a previously unsuspected role
and clinical models of breast cancer metastasis.
of miR-200s in promoting metastatic colonization,
Additionally, it revealed a dichotomous role for
our findings also established a new paradigm
the miR-200 family at different stages of metas-
in
tatic progression.
influences tumor metastasis by regulating not
which
epithelial-mesenchymal
plasticity
only the intrinsic characteristics of tumor cells,
Earlier studies by our group and others identified
but also their extrinsic interactions with their
the miR-200 family miRNAs as suppressors
microenvironment.
of EMT and tumor invasion that function via
one of the first successful applications of high
direct targeting of Zeb1 and Zeb2, which are
throughput proteomic profiling in the study of
well established master regulators of EMT
cancer metastasis.
and transcriptional repressors of E-cadherin.
This study also represents
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RESEARCH FUNDING
2. Tiede B and Kang Y. (2011) From milk to
malignancy: the role of mammary stem cells
Source: NIH (NCI)
in development, pregnancy and breast cancer.
Title: Metadherin in Metastasis and Chemo-
Cell Res., 21(2):245-57.
resistance of Breast Cancer
Total Period: 9/1/08-8/31/13
3. Sethi N, Dai X, Winter CG, and Kang Y.
(2011)
Source: NIH
Tumor-derived
Jagged1
promotes
osteolytic bone metastasis of breast cancer
Title: The Role of miRNAs in Epithelial Mesen-
by activating stromal Notch signaling. Cancer
chymal Transition and Metastasis
Cell, 19(2):192-205. (Cover Article)
Total Period: 4/1/10-3/30/15
Editorial by: Tao J, Erez A, Lee B. Cancer
Cell, 19(2):192-205. Recommended by Faculty
Source: Champalimaud Foundation
of 1000.
Title: Champalimaud Metastasis Program at
Princeton University
4. Blanco MA and Kang Y. (2011) Signaling
Total Period: 5/1/09-4/30/2014
pathways in breast cancer metastasis – novel
Source: New Jersey Commission on Cancer
Cancer Res., 13:206.
insights from functional genomics. Breast
Research
Title: Targeting Notch Signaling in Breast Cancer
5. Matsushima K, Isomoto H, Yamaguchi N,
Metastasis
Inoue N, Machida H, Nakayama T, Hayashi
Total Period: 6/26/09-6/25/11
T, Kunizaki M, Hidaka S, Nagayasu T,
Nakashima M, Ujifuku K, Mitsutake N,
Source: Breast Cancer Alliance Exceptional
Ohtsuru A, Yamashita S, Korpal M, Kang Y,
Project Grant
Gregory PA, Goodall GJ, Kohno S, Nakao K.
Title: The role of VCAM1 in the activation of
(2011) MiRNA-205 modulates cellular inva-
dormant breast cancer bone micrometastasis
sion and migration via regulating zinc finger
Total Period: 1/1/11-12/31/11
E-box binding homeobox 2 expression in
esophageal squamous cell carcinoma cells.
Source: Susan G. Komen for the Cure
J. Transl. Med., 9(1):30.
Title: Targeting VCAM1 to prevent metastatic
recurrence from dormant bone micrometastases
Total Period: 11/28/11-11/27/14
6. Shan J, Budjiono SJ, Hu G, Yao N, Kang Y,
Ju Y, and Prud’homme RK. (2011) PEGylated
composite nanoparticles containing upconverting
PUBLICATIONS
phosphors
and
meso-tetraphenyl
porphine (TPP) for photodynamic therapy.
Adv. Funct. Mater., 21:2488-2495.
7. Blanco MA, Alečković M, Hua Y, Li T, Wei Y, Xu
1. Tamasi J, Zhang X, Lu X, Zhu J, Chen H,
Z, Cristea I, and Kang Y. (2011) Identification
Tian X, Lee T-C, Threadgill DW, Kream BE,
of Staphylococcal nuclease domain containing
Kang Y, Partridge NC, and Qin L. (2011) In
1 (SND1) as a Metadherin-interacting protein
vivo epidermal growth factor receptor plays
with metastasis-promoting functions. J. Biol.
an anabolic role in bone metabolism. J. Bone
Chem., 286:19982-92.
Miner. Res., 26:1022-34.
8. Mercatali L, Ibrahim T, Sacanna E, Flamini E,
Scarpi E, Calistri D, Ricci M, Serra P, Ricci R,
Zoli W, Kang Y, and Amadori D. (2011) Bone
Seton-Rogers S. (2011) Nature Reviews
Cancer, 12: 920.
Haas MJ. (2012) SciBX, 5(2):1-2.
metastases detection by circulating biomarkers:
OPG and RANK-L. Int. J. Oncol., 9(1):30.
14. Sethi N and Kang Y. (2011) Notch signaling
in cancer progression and bone metastasis.
9. Lu X and Kang Y. (2011) Cell fusion hypothesis
Br. J. Cancer, 105:735-48.
of cancer stem cell. Adv Exp Med Biol.
714:129-140.
15. Sethi N and Kang Y. (2011) Notch signaling:
mediator and therapeutic target of bone
10. Ibrahim T, Sacanna E, Gaudio M, Mercatali
metastasis. IBMS BoneKEy, 8(10):
L, Scarpi E, Zoli W, Serra P, Ricci R, Serra
L, Kang Y, Amadori D. (2011) Role of RANK,
16. Koh B and Kang Y. (2012) The pro-metastatic
RANKL, OPG, and CXCR4 Tissue Markers in
role of bone marrow-derived stromal cells:
Predicting Bone Metastases in Breast Cancer
a focus on MSCs and Tregs. EMBO Report,
Patients. Clin. Breast Cancer. 11(6):369-75.
13(5):412-22.
11. Korpal M, Ell BJ, Buffa FM, Ibrahim T,
17. Blanco MA, LeRoy A, Khan Z, Alečković M,
Terrasa AC, Mercatali L, Khan Z, Blanco
Zee BM, Garcia BA, and Kang Y. (2012) Global
MA, Goodarzi H, Hua Y, Wei Y, Hu G, Garcia
secretome analysis identifies novel mediators
B, Ragoussis J, Amadori D, Harris AL, and
of bone metastasis. Cell Res., Jun 12. doi:
Kang Y. (2011) Direct targeting of Sec23a by
10.1038/cr.2012.89. [Epub ahead of print]
miR-200s influences cancer cell secretome
and promotes metastatic colonization. Nature
18. Celià-Terrassa T, Meca-Cortés Ó, Mateo F,
Medicine, 17:1101–1108. (Cover highlight)
Martínez de Paz1 A, Rubio N, Arnal-Estapé A,
Editorial by: Thompson EW and Haviv I.
Ell, BJ, Bermudo R, Díaz A, Guerra-Rebollo,
(2011) Nature Medicine, 17:1048–1049.
Zaromytidou AI. (2011) Nature Cell Biol.,
13:1294.
McKenna ES. (2011) Cancer Discovery, 1:28
Lozano JJ, Estarás C, Milà J, Vilella R,
Paciucci R, García de Herreros A, Gomis RR,
Kang Y, Blanco J, Fernández PL, and Thomson
TM. (2012) Epithelial-mesenchymal transition can suppress major attributes of epithe-
12. Sethi N and Kang Y. (2011) Unraveling
the complexity of metastasis: molecular
lial tumour-initiating cells. J. Clin. Invest.,
122(5):1849-68.
understanding and targeted therapeutics.
Nature Reviews Cancer, 11(10):735-748. (Part
19. Peinado H, Alečković M, Lavotshkin S, Costa da
of the “The next 10 years” special series)
Silva B, Moreno-Bueno G, Hergueta-Redondo
13. Lu X, Mu E, Riethdorf S, Yang Q, Wei Y,
M, Williams C, García-Santos G, Ghajar CM,
Yuan M, Yan J, Hua Y, Tiede BJ, Lu X, Reiss
Nitadori-Hoshino A, Hoffman C, Badal K,
M, Haffty BG, Pantel K, Massagué J, and
Garcia BA, Callahan MK, Yuan J, Martins VR,
Kang Y. (2011) VCAM1 promotes osteolytic
Skog J, Kaplan RN, Brady MS, Wolchok JD,
expansion of indolent bone micrometastases
Chapman PB, Kang Y, Bromberg J, Lyden D.
of breast cancer by engaging α4β1-positive
(2012) Melanoma-derived exosomes educate
osteoclast progenitors. Cancer Cell, 20:701-
bone marrow progenitor cells toward a
714. (Featured Article)
pro-metastatic phenotype. Nature Medicine,
Editorial by: Hynes RO. (2011) Cancer Cell,
20:689-690.
May 27. doi: 10.1038/nm.2753. [Epub ahead
of print]
86/87
20. Chakrabarti R, Wei Y, Romano R, DeCoste C,
Kang Y, and Sinha S. (2012) Elf5 regulates
mammary gland stem/progenitor cell fate
MEETINGS & SEMINARS
Meetings Organized
by influencing Notch signaling. Stem Cells,
Jul;30(7):1496-508.
doi:
10.1002/stem.1112.
[Epub ahead of print]
11th Annual Conference of Cancer-Induced Bone
Disease
Chicago, IL, November, 2011
21. Wendt MK, Schiemann BJ, Parvani JG, Lee
Y-H, Kang Y, Schiemann WP. (2012) TGF-β
Yibin Kang, Co-organizer and member of scientific
committee
stimulates Pyk2 expression as part of an
epithelial-mesenchymal transition program
2012 Annual Meeting of the American Association
required for metastatic outgrowth of breast
for Cancer Research (AACR)
cancer. Oncogene, in press.
Chicago, IL, USA April 2012
Yibin Kang, Member of the Scientific Committee
HONORS AND AWARDS
Yibin Kang:
Chair of the Major Symposium on miRNAs in
Cancer Progression
2013 Annual Meeting of the American Association
for Cancer Research (AACR)
• 2011 Vilcek Prize for Creative Promise in
Washington DC, USA April 2012
Yibin Kang, Member of the Scientific Committee
Biomedical Science (Yibin Kang)
• 2012 AACR Award for Outstanding Achieve
ment in Cancer Research (Yibin Kang)
Invited presentations
• 2012 Promotion to Full Professor (Yibin Kang)
• 2012 Promotion to Warner Lambert-Parke Davis
Professor (Endowed Chair) (Yibin Kang)
Postdoctoral Fellows:
• 2011 Department of Defense Postdoctoral Fello
wship (Rumela Chakrabarti)
• 2012 Komen for the Cure Postdoctoral Fello
wship (Hanqiu Zheng)
Graduate Students:
• 2011 Thomas Silhavy Graduate Student Award
(Brian Ell)
• 2012 Charlotte Elizabeth Procter Honorific Fello
wship (Liling Wan)
Yibin Kang has given invited lectures on
breast cancer metastasis in the following
meetings and seminars:
1. Champalimaud Cancer Centre Symposium,
Champalimaud Foundation, Lisbon, Portugal
(1/14/2011)
2. Department of Physiology, Tufts University
School of Medicine, Boston, MA (3/8/2011)
3. 12th World Conference, Fudan University
Alumni Association (5/7/2011)
4. Mary Babb Randolph Cancer Center, West
Virginia University, Morgantown, WV (5/11/2011)
5. Department of Hematology and Oncology,
University of Freiburg, Germany (5/20/2011)
6. The Gordon Research Seminar (GRS) and
Gordon Research Conference (GRC) on “Bones &
Undergraduate Students:
• 2012 Molecular Biology Department Award for
Outstanding Thesis Research (Lenka
Ilcisin)
Teeth”, Les Diablerets, Switzerland (6/18/2011)
7. Champalimaud-TuMic Metastasis Research
Meeting, Lisbon, Portugal (6/26/2011)
8. Bristol-Myers Squibb, Princeton, NJ (7/13//2011)
9. 13th International Symposium of the Society of
26.Distinguished Cancer Biology Seminar Series,
Chinese Bioscientists in America, Guangzhou,
Texas Tech University Health Science Center,
China (7/28/2011)
Amarillo, TX (1/18/2012)
10.Sun Yat-Sen University Cancer Center, Guangzhou, China (7/29/2011)
11.The 9
th
Sciences, Amsterdam, Netherlands (1/26/2012)
Biannual Conference of Chinese
Biological Investigator Society, ZhangJiaJie,
China (7/31/2011)
Florida (8/5/2011)
dorf, Hamburg, Germany (1/28/2012)
Cancer Center, Houston, TX (2/7/2012)
30.Department of Pediatrics, M.D. Anderson
13. 2011 FASEB meeting on TGF-β Signaling in
Development and Disease, Lucca, Italy (8/21/2011)
14.3rd International Tumor Progression and Metastasis Kloster Seeon Meeting, Seeon, Germany
(9/19/2011)
15.Department of Cellular and Structural Biology,
University of Texas Health Science Center, San
Antonio, TX (10/4/2011)
16.Genome Institute of Singapore, Singapore
(10/11/2011)
University
28.University Medical Center Hamburg-Eppen29.Metastasis Research Center, M.D. Anderson
12.The 6th DOD Era of Hope Meeting, Orland,
17.Zhejiang
27.Royal Netherlands Academy of Arts and
School
of
Medicine,
Hangzhou, China (10/19/2011)
18.Shanghai Jiao Tong University School of
Medicine, Shanghai, China (10/21/2011)
19.Fox Chase Cancer Center, Philadelphia, PA
(10/29/2011)
20.1st NIBB - Princeton Symposium “Proteomics,
Metabolomics, and Beyond”, Okazaki, Japan
(11/2/2011)
21.The 5th Japan & US Collaboration Conference in
Cancer Center, Houston, TX (3/13/2012)
31.Immunology and Cancer Biology Seminar
Series, Cedars-Sinai Medical Center, Los
Angeles (3/23/2012)
32.Robert H. Lurie AACR Scholars Symposium,
Northwestern University, Chicago, IL (3/30/2012)
33.103rd AACR Annual Meeting, Chicago, IL
(4/1/2012)
34.SAPA Symposium on Translational Medicine,
Princeton, NJ (4/14/2012)
35.National Breast Cancer Coalition’s (NBCC) Annual
Advocate Summit, Arlington, VA (5/6/2012)
36.National Cancer Institute-Frederick (5/7/2012)
37.2nd International Conference: Translational Research in Oncology, Forlì, Italy (5/9/2012)
38.Hepatic metastasis symposium, Champalimaud
Center, Lisbon, Portugal (5/12/2012)
39.National Institute of Biological Sciences,
Beijing, China (5/21/2012)
Gastroenterology, Tokyo, Japan (11/10/2011)
40.Tsinghua University, Beijing, China (5/22/2012)
22.Department of Developmental Biology and Can-
41.Ohio State University Comprehensive Cancer
cer Research, Hadassah School of Medicine,
Hebrew University, Jerusalem, Israel (11/17/2011)
23.Keynote lecture at the Annual Retreat of the
Proteases and Cancer Program, The Barbara
Center, Columbus, Ohio (6/6/2012)
42.Fourth International Conference on Osteoimmunology: Interactions of the Immune and
Skeletal Systems, Corfu, Greece (6/18/2012)
Ann Karmanos Cancer Institute, Detroit, MI
(12/1/2011)
24.11
th
Annual Conference of Cancer-Induced
Bone Disease, Chicago, IL (12/2/2011)
25.Department of Oncological Sciences, Mount Sinai
School of Medicine, New York, NY (1/10/2012)
Yibin Kang has been invited to give lecture
at the following upcoming meetings and
seminars:
43.Molecular Cancer Therapeutics Conference,
Princeton, NJ (7/16/2012)
88/89
44.Friedrich Miescher-Institute for Biomedical
Research, Basel, Switzerland (7/25/2012)
54.Xiamen University, Xiamen, China (11/13/2012)
55.3rd International Conference on Cellular Dyna-
45.Gordon Conference on Notch Signaling in
mics & Chemical Biology, Hefei, China (11/15/2012)
Development, Regeneration & Disease, Lewiston,
56.2012 CTRC-AACR San Antonio Breast Cancer
ME (8/12/2012)
46.The 14
th
International Biennial Congress of
the Metastasis Research Society, Brisbane,
Australia (9/4/2012)
47.1st ACTC “Advances in Circulating Tumor
Cells” meeting, Athens, Greece (9/26/2012)
48.Department of Pharmacology and Physiology, Drexel University College of Medicine,
Philadelphia, PA (10/2/2012)
49.The Herrenhausen Symposium on Metastasis,
Seeon, Germany (10/10/2012)
50.Korean Society of Molecular and Cellular Biology
2012 meeting, Seoul, Korean (10/12/2012)
51.World Oncology Forum, Lugano, Switzerland
(10/26/2012)
Symposium, San Antonio, TX (12/5/2012)
57.Department of Biology, Massachusetts Institute
of Technology, Cambridge, MA (12/11/2012)
58.Department of Cell Biology, Albert Einstein
College of Medicine, Bronx, NY (12/19/2012)
59.Department of Chemical Biology and Therapeutics, St. Jude Children’s Research Hospital,
Memphis, TN (1/10/2013)
60.AACR Special Conference on Tumor Invasion
and Metastasis San Diego, CA (1/22/2013)
61.Pathway in Development and Cancer Conference,
Freiburg, Germany (2/20/2013)
62.AACR-SNM Joint Conference on Molecular
Imaging in Cancer Research, San Diego, CA
(3/1/2013)
52.Zhejiang University, Hangzhou, China (11/8/2012)
63.Cancer Biology & Genetics Program, Memorial
53.Ray Wu Award Symposium, Hangzhou, China
Sloan-Kettering Cancer Center, New York, NY
(11/9/2012)
(4/19/2013)
David Lyden M.D., Ph.D.
Joon-Hyung Kim
Weill Cornell Medical College
Rachel Feder
(Medical Student, Weill Cornell Medical College)
(Medical Student, Stonybrook University)
Group members
Jeffrey Greenfield MD/PhD (Assistant Professor/
Neurosurgery, Matthew Larson Foundation)
Tang-Long Shew MD
(Tenured Professor, Sabbatical, University of
Taiwan)
Maria de Sousa PhD (Adjunct Professor, Weill
Cornell Medical College)
Hector Peinado PhD
(Champalimaud Foundation Instructor)
Helene Brazier PhD
(Department of Defense Post-Doc)
Yujie Huang PhD
(Post-Doc)
Rachel Ruden
(DVM, PhD Student, UPENN Veterinary College)
Sophia Ceder
(Visiting PhD scholar-Karolinska Institute)
Scott Kerns
(Lab Manager)
Caitlin Williams
(Technician)
Lavon Dirickson
(Executive Assistant)
Overall Summary
Our laboratory investigates the cellular and
Haiying Yhang
molecular pathways that contribute to the tumor
(Post-Doc)
and metastatic microenvironments. In response
Irina Matei
(Post-Doc)
to tumor-derived secreted factors, we have
determined that bone marrow-derived stem and
progenitor cells initiate neovasculogeneis and
Irini Bournazou
promote the formation of the “pre-metastatic
(AHEPA Foundation Post-Doc)
niche” at future sites of metastasis providing
Bruno de Costa Silva
(Manning Foundation Post-Doc)
a favorable microenvironment for the growth
of metastatic tumor cells.
Although secreted
factors are known contributors to bone marrow
Ayuko Nitadori
progenitor cell mobilization to the pre-metastatic
(Manning Foundation Post-Doc)
niche, the role of tumor-derived microparticles
Guillermo Garcia Santos
known as exosomes in this process is not known.
(Clarin Ayudas Post-Doc, Principality of Asturias)
Prajwal Rajappa MD
(Department of Neurosurgery Post-Doc)
Tumor exosomes are small microvesicles that
contain mRNAs, microRNAs, and proteins as new
factors in the crosstalk between tumor cells and
cells in the tumor microenvironment especially
Karen Badel MD
bone marrow progenitor cells. Tumor exosomes
(Department of Neurosurgery Post-Doc)
‘educate’ bone marrow progenitor cells towards
Yisi Wang PhD
(Visiting Post-Doc, Sichuan University)
a pro-vasculogenic and pro-metastatic phenotype
through the upregulation of the MET oncoprotein.
We have defined an exosome signature consisting
Rosario Andre MD
of tyrosinase-related protein 2, VLA-4 integrin,
(American Portuguese Biomed. Res. Fund/
Hsp70/90 and the Met oncoprotein representative
Champalimaud Foundation PhD student)
of exosomes in patient with Stage IV melanoma
90/91
with distant metastasis. In addition, melanoma
exosomes with tyrosinase-related protein 2 and
the MET oncoprotein were useful in predicting
Clinical Value of Circulating Exosome
Protein Levels and Content in Melanoma
Patients
which patients with Stage III disease (lymph node
involvement) would then go on to Stage IV disease.
During the past few years, the Lyden laboratory
Our results show that tumor-derived exosomes
has developed and standardized methods to
can alter the bone marrow in a durable manner
isolate exosomes from fresh as well as frozen
suggesting that genetic or epigenetic changes
plasma isolated from cancer patient blood.
could be involved in this phenomenon, as bone
To determine the significance of circulating
marrow cells retain the educated phenotype.
exosomes in metastasis, we focused on metastatic
We identify the exosome-mediated transfer of
melanoma. We isolated exosomes from the plasma
the oncoprotein MET as a key regulator of bone
of Stage I-IV melanoma patients by standard
marrow education, recruitment, and metastatic
ultracentrifugation or sucrose cushion flotation
progression.
methods. Patient exosomes were characterized
by electron microscopy (Fig.1A), flow cytometry
and western blot analysis of common exosome
Circulating Tumor-derived Exosomes
markers, such as CD63, CD9 and MHC-I, as
Soluble factors such as vascular endothelial
well as melanoma markers tyrosinase-related
growth factor (VEGF-A), placental growth
peptide 2 (TYRP-2) (data not shown). Exosome
factor (PlGF), transforming growth factor-β
size distribution and number were quantified
(TGF-β), tumor necrosis factor-α (TNF-α), and
using a nanoparticle tracking system (NanoSight
lysyl oxidase (LOX) play an active role in the
analysis). The levels and composition of the cargo
recruitment of bone marrow-derived progenitor
of exosome proteins were higher and distinct
cells (BMDCs) to the tumor and pre-metastatic
in patients with Stage IV disease compared to
niches.
vesicle-based
normal controls and patients with less advanced
information transfer by exosomes have changed
Recent
disease (Fig.1B). These data suggested that there
our view of the tumor microenvironment.
was a quantitative and qualitative difference in
Exosomes are small vesicles (40-100 nm)
protein content in exosomes from patients with
derived from the luminal membranes of the
metastatic disease. By examining exosomes
late endosomes/multivesicular bodies (MVB),
obtained from melanoma patients, we have
constitutively released via the fusion of MVBs
identified a “melanoma exosome signature”
with the cell membrane. Exosomes are now
consisting of heat shock proteins (HSP70/90), α4β1
considered bona fide biologically active entities
-integrin (VLA-4, also known as FN receptor),
and together with soluble factors, chemokines
and TYRP-2 that distinguish melanoma-derived
and hormones, represent the main extracellular
exosomes from normal exosomes (Fig.1C) and
signals
findings
implicated
in
on
the
regulation
of
multiple physiological processes. In cancer,
exosomes
are
involved
in
supporting
the
tumor microenvironment, promoting invasion,
angiogenesis and metastatic behavior. Therefore,
exosomes could be considered one of the major
forces acting either locally or systemically to
promote the continuous crosstalk between the
tumor and its microenvironment, influencing the
behavior of different cell types such as stromal,
endothelial and bone marrow (BM) cells.
may identify patients at high risk for metastatic
for the arrival and colonization by cells from
disease. Kaplan-Meier analysis of the total amount
the primary tumor at distant metastatic sites.
of protein in circulating exosomes from Stage IV
Our data showed that the integrin VLA-4
melanoma patients demonstrated that the amount
(α4β1) is involved in recruitment of BM-derived
of exosome protein content correlated with disease
VEGFR1+ CD11b+ MMP9+ HPCs to form cellular
outcome, as patients with exosome protein levels
clusters within the tissue parenchyma at sites of
in excess of 50 µg/ml had a significantly poorer
upregulated fibronectin (FN). Significantly, and
outcome (Fig.1D). These data provide promising
of equal importance, is the recruitment of BMDCs
support for the use of this simple blood test to
to the immediate surrounding microenvironment
predict outcome and suggest that investigating
of the primary tumor. Endothelial progenitor cells
the levels of exosome proteins in the blood of Stage
(EPCs) migrated to sites immediately adjacent
III patients with lymph node involvement may be
to the primary tumor contributing to de novo
predictive of disease progression.
generation of vessels.
Bone Marrow-derived Cells (BMDCs)
and Metastasis
“Re-education” by Exosomal Cargo
Evidence
decade
BM cells, we injected naïve C57BL/6 wild-type
supports a crucial role for cells in the surrounding
mice intravenously with exosomes derived from a
tumor microenvironment as critical components
syngeneic, metastatic mouse mammary tumor cell
regulating primary tumor growth and metastatic
line (EO771) every other day for 14 days. EO771-
behavior. Both progenitor and differentiated cells
derived exosomes reached organs such as the
originating from the BM were found to play a
lung and the BM (Fig.2A), and fused with BMDCs
central role in tumor malignancy and metastasis.
as we have observed previously for melanoma
Studies in our laboratory demonstrated that
exosomes. Tumor cell-derived exosomes can also
clusters of vascular endothelial growth factor 1
transfer receptors between tumor and BM cells.
(VEGFR1)-expressing hematopoietic progenitor
In fact, incubation of metastatic melanoma
cells (HPCs), are mobilized from the BM through
exosomes, which contain very high amounts of
influence from soluble factors secreted by the
Itgb1, with Lin- BM progenitor cells (BMPCs)
primary tumor. HPCs home to pre-metastatic
revealed: a) dramatic uptake of these exosomes
organs in preparation (i.e. pre-metastatic niche)
by Lin- BMPCs, b) subsequent upregulation of α4β1
accumulated
in
the
past
To establish whether BC exosomes interact with
92/93
integrin in BMPCs and c) enhanced engraftment of
distant metastases at diagnosis. Remarkably, the
fibronectin (FN) (Fig.2B). Pre-treatment of mice
5-year survival rate is only 40%, compared to the
with exosomes derived from highly metastatic
85% survival rate among non-IBC patients.
B16-F10 cells systemically resulted in enhanced
metastasis of the weakly metastatic B16-F1
IBC accounts for 3 to 10% of diagnosed breast
variant to a broader array of tissues. Neutralizing
carcinomas. However, the importance of studying
exosome Itgb1 with a blocking antibody inhibited
IBC is underlined by the fact that non-IBC primary
exosome uptake and subsequent α4β1 upregulation
lesions often recur with the IBC signature
by BMPCs, and blocked the construction of pre-
phenotype (i.e. tumor emboli found predominantly
metastatic sites by B16-F10 exosomes. Therefore
in lymph and blood vessels) and locally advanced
Itgb1, which is highly expressed in exosomes from
non-IBC successfully treated with neoadjuvant
metastatic melanoma and breast cancer cells,
chemotherapy
mediated exosome transfer to BMPCs, altered their
exclusively in the lymphovasculature. Therefore,
surface expression, and enhanced their ability
treatment strategies developed for IBC could be
to seed FN-rich environments and remodel sites
widely applicable for all BCs that do not remain
within distant tissues that favor colonization.
organ-confined.
The Role of Exosomes in Other Tumor
Models: Inflammatory Breast Cancer (IBC)
The IBC pre-clinical model, MARY-X
often
shows
residual
emboli
The human IBC xenograft model, MARY-X,
Inflammatory breast cancer (IBC) is the most
precisely captures the IBC signature phenotype
lethal form of primary breast cancer. Clinically,
in that the tumor emboli grow exclusively
IBC presents with skin findings that include
within the murine lymph and blood vessels,
erythema, peau d’orange (dimpling of thickened
and, in addition, replicate the clinical features of
skin) and regional warmth (Fig.3A). Clinical
erythema (Fig.4 A-C). Both the MARY-X in vitro
features of IBC are due to the signature
spheroids and in vivo tumor emboli form on the
phenotype of IBC, that of extensive intravasation
basis of an, overexpressed, intact E-cadherin/
in situ of the lymphatic and blood vessels by
α,β-catenin axis and exhibits a gain in cellular
tumor emboli (Fig.3B). Importantly, IBC most
organization. The molecular feature, namely
often presents without an associated mass or
the persistent overex-pression of the intact,
invasion of neighboring stroma (i.e. no invasion
E-cadherin/α,β-catenin axis is also consistent with
of the stroma tissue) (Fig.3B). Almost all women
human IBC. MARY-X is the only pre-clinical model
with primary IBC have lymph node involvement
of IBC having captured the signature phenotype
and approximately 25% of patients with IBC have
of tumor emboli found exclusively within lymph
and blood vessels. Of equal importance is that the
present in extremely high levels in both MARY-X
tight compact in vitro MARY-X spheroids mimic
spheroids and tumor emboli and may have the
the in vivo emboli providing an in vitro model with
capacity to recruit and differentiate circulating
tractable in vivo applications.
progenitor cells.
IBC/MARY-X
is
highly
metastatic;
however,
Preliminary data of our lab have showed that
metastasis is via an invasion-independent (no
progenitor cells play a major role in the process
epithelial-to-mesenchymal transition; EMT) and
of lymphovasculogenesis in inflammatory breast
passive dissemination of tumor emboli. The
cancer. Key to this process is the influence of
absence of EMT of IBC/MARY-X and preliminary
tumor emboli-derived soluble factors, namely
data strongly suggest a progenitor cell recruitment-
exosomes and the capacity of the exosome cargo
-dependent manner for de novo generation of
to “re-educate” progenitor cells.
vessels (e.g. achievement of lymphovasculogenesis).
our preliminary analysis of circulating exosomes
Previous studies have shown that IBC “short
in breast cancer (BC) patient blood specimens
circuits” the canonical pathway of intravasation
also showed that exosome protein levels (per mL
(i.e. invasion to achieve hematogenous entry)
plasma) are significantly higher in inflammatory
where the tumor emboli generate neovessels
breast cancer (IBC), the more aggressive BC with
through recruitment of BMDCs, which form around
poor-prognosis in comparison to BC patients
the tumor emboli. Central to the recruitment of the
of both receptor status negative and the lower
BMDCs for neovascularization is tumor emboli-
risk group (estrogen receptor positive; ER+)
secreted soluble factors. Preliminary data strongly
irrespective of tumor size.
have suggested tumor emboli-derived exosomes,
Importantly,
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RESEARCH FUNDING
I) NCI UO1 TMEN grant
V II) Malcolm Hewitt Wiener Foundation
“Characterization and Functional Analysis
“The role of exosome-derived genomic transfer”
of Breast Cancer Secreted Exosomes in
4/1/11-5-1-14
Malignant Progression” [NCI investigator
David Lyden PI
for exosome study in the tumor microenvironment network]
V III)Mary Kay Foundation Grant
8/1/12-7/31/17
“The role of bone marrow-derived proge-
David Lyden PI
nitor cells in malignant progression of
inflammatory breast disease”
II) NCI U54CA143836 Tumor Microenvironment
Network, PSOC Pilot Project
1-2-12 to 12-30-14
David Lyden PI
“Engineering a Model of the Bone Marrow
Microenvironment to Identify Mediators
IX) Beth C. Tortolani Foundation
of Breast Cancer Dormancy and Drug
“The molecular signature of inflammatory
Resistance”
breast cancer”
7-1-12-6-30-13
6/1/11-7-1-14
David Lyden PI
PIs: Lyden-Norton-Hudis-Bromberg-Chiosis
III) The Hartwell Foundation
“The role of IL-17 in exosomal transfer”
7/1/12-6/30/15
PUBLICATIONS
Refereed Journal Articles
David Lyden PI
Acharya SS, Kaplan RN, MacDonald D, Fabiyi
IV) Department of Defense, Breast Cancer
OT, DiMichele D, Lyden D. Neo-angiogenesis
Division “Unraveling the implication of the
contributes to the development of hemophilic
hematopoietic stem cells in bone metastasis
synovitis. Blood, 2011 117(8):2484-2493.
of breast cancer”
1/1/11-2/1/14
Polkinghorn WR, Dunkel IJ, Souweidane MM,
David Lyden PI
Khakoo Y, Lyden DC, Gilheeney SW, Becher OJ,
Budnick AS, Wolden SL. Disease Control and
V) Manning Foundation
“The role of bone marrow-derived cells in
cardiac valvular genesis”
7/1/11-8-1-14
David Lyden PI
VI) Manning Foundation
“Exosomes promoting blood-brain barrier
breakdown and neurological disorders”
8/1/12-7/31/14
David Lyden PI
Ototoxicity Using Intensity-Modulated Radiation
MEETINGS, COURSES, SEMINARS
Therapy Tumor-Bed Boost for Medulloblastoma.
Zhang H, Peinado H, Hoffman C, Williams C, Kim
Int J Radiat Oncol Biol 2011, 81(3): e15-20.
JH, Nitadori-Hoshino A, Blattner M, Yu H, Hearn
Matei I, Ghajar CM, Lyden D. A TeNaCious
S, Silva JM, Elemento O, Greenfield J, Boockvar
Foundation for the Metastatic Niche. Cancer Cell,
JA, Rubin MA, Brady MS, Wolchok JD, Chapman
2011 20(2):139-141.
PB, Riely GJ, Bromberg J, Lyden D. Tumorderived exosomes contain DNA and demonstrate
Azare J, Doane A, Leslie K, Chang Q, Berishaj M,
correlation with tumor malignancy and diagnostic
Nnoli J, Mark K, Al-Ahmadie H, Gerald W, Hassimi
value by facilitating non-invasive detection of
M, Viale A, Stracke M, Lyden D (corresponding
genetic mutations in cancers. Nature Genetics,
author), Bromberg J. Stat3 mediates expression
Under Review.
of autotoxin in breast cancer. PLoS One, 2011
6(11):e27851).
Meetings Organized
Peinado H, Lavtoshkin S, Lyden D. The secreted
Session Chair/Speaker
factors responsible for pre-metastatic niche
Keystone Symposia on Stem Cells, Cancer and
formation: Old sayings and new thoughts. Semin
Metastasis
Cancer Biol, 2011 21(2):139-146.
Keystone, Colorado
March 2011
Psaila B, Lyden D, Roberts I. Megakaryocytes,
malignancy and bone marrow vascular niches.
Educational Committee Chairman
Journal of Thrombosis and Haemostasis, 2012,
AACR Annual Meeting
10(2): 177-188.
“Emerging Role of Exosomes in Cancer Invasion
Peinado H, Aleckovic M, Lavothskin S, Costa da
and Metastasis”
Silva B, Moreno-Bueno G, Hergueta-Redondo M,
Orlando, FL
Williams C, Matei I, Garcia-Santos G, Nitadori-
April 2011
Hoshino A, Hoffman C, Garcia BA, Callahan
MK, Yuan J, Martins VR, Kaplan R, Brady MS,
Visiting Lecturer/Organizer
Wolchok JD, Chapman PB, Kang Y, Bromberg JF,
StratCan Summer School for Post-Doctoral Fellows
Lyden D. Melanoma-derived exosomes educate
Karolinska Institutet
bone marrow progenitor cells toward a pro-
Stockholm, Sweden
metastatic phenotype through upregulation of the
June 2011
MET oncoprotein. Nature Medicine (article), 2012.
[Nature Medicine ‘News and Views’; Nature
Organizing Committee Member
Reviews Cancer ‘Highlight’; Cancer Discovery;
New Concepts in Cancer Metastasis
Science Signaling].
TuMIC/European Union
Lisbon, Portugal
Peinado H, Psaila B, Ghajar C, Cox T, Bromberg
June 2011
J, Maru Y, Huelsken J, Karin M, Semenza G,
Bissell M, Erler J, Ferrara N, Hiratsuka S,
Session Chairperson
Lyden D. The Pre-Metastatic Niche and Organ-
Tumor Microenvironment Complexity: Emerging
Specific Metastasis. Nature Reviews Cancer, In
Roles in Cancer Therapy
Press.
Orlando, Florida
November 2011
96/97
Invited presentations
Invited Speaker
Honored Lecturer
Scholars
MD Anderson Cancer Center
The Rockefeller University
Houston, Texas
New York, New York
February 2011
January 2012
Keynote Speaker
Post-Doc Day University Speaker
11 Annual Immunology Conference
Berkeley Laboratories
Roswell Park Cancer Institute
Berkeley, California
Buffalo, New York
April 2012
Seminars in Clinical Research series for Clinical
th
September 2011
Alumni Grand Rounds Speaker
Invited Speaker
Duke University Medical Center
Beatson Institute
Durham, North Carolina
Glasgow, Scotland
October 2011
July 2012
Invited Speaker
I.J. “Josh” Fidler Innovation in Metastasis
Advanced
Breast
Cancer
First
Consensus
Research Award and Lecture
Conference
Metastasis Research Society and Anti-Cancer, Inc.
Lisbon, Portugal
Brisbane, Australia
November 2011
September 2012
Prémio António
Champalimaud
de Visão
6. Prémio António Champalimaud de Visão
6.1. Reunião do Júri e selecção dos premiados
6.2. Cerimónia de atribuição do Prémio
6.4. Conferência sobre o Prémio António Champalimaud de Visão na ARVO
Presidente Cavaco Silva entrega o troféu ao
Dr. Paul-Samson Lusamba-Dikassa, Director do APOC
Prémio António
Champalimaud de Visão
6.1. Reunião do Júri e selecção
dos premiados
indivíduos em alto risco de infecção na África subsariana.
Em 2011 os membros do Júri reuniram-se nas instala-
rurais, muito pobres e situadas em locais geográficos
ções do Centro da Fundação Champalimaud, em
distantes.
Um projecto vastíssimo que cobre mais de 16 países
africanos e que envolve milhares de comunidades
Lisboa, para a decisão final sobre o premiado de 2011,
num processo de selecção em várias fases, que se
Esta organização utiliza uma fórmula única para dar
iniciou em Janeiro, logo após o fecho de recepção
resposta eficaz a esta gigantesca tarefa: trata-se de um
das candidaturas.
processo denominado “Community Directed Treatment
with Ivermectin” (CDTI), que atribui a responsabilidade
O Prémio António Champalimaud de Visão 2011 foi atri-
da distribuição da medicação directamente às comu-
buído ao African Programme for Onchocerciasis Control
(APOC), uma extraordinária organização sediada no
Burkina Faso, criada em 1995 com o objectivo de eliminar
a oncocercose, mais conhecida pela “cegueira dos rios”,
bem como outras infecções provocadas pelo parasita
Onchocerca volvulus, considerado um problema de saúde
pública e de enorme peso social e económico em África.
Através da sua rede de estruturas de apoio, o APOC
consegue assegurar o tratamento regular de cerca de 57
milhões de pessoas e protege mais de 100 milhões de
Reunião do Júri do Prémio António Champalimaud
de Visão, na Fundação Champalimaud
100/101
nidades que dela beneficiam, promovendo, deste modo,
precisarem e enquanto for necessário, centros de
um sentido de co-responsabilidade e auto-suficiência
investigação e a enorme relevância da autoparticipação
nestes grupos.
das mais de 120 000 comunidades onde este flagelo é
endémico.
A verdadeira força deste programa está na sua capacidade de criar parcerias, que incluem 20 países e
Esta fórmula cria os meios para que seja possível, dentro
organizações doadoras, 15 organizações não governa-
de um período de tempo realista, eliminar, de forma
mentais, 19 países africanos participantes, a farma-
permanente, a transmissão do parasita Onchocerca
cêutica Merck & Co. Inc., que fornece gratuitamente
volvulus e deixar assim de ser eventualmente neces-
o medicamento Ivermectin/Mectizan a todos os que
sário o tratamento continuado da oncocercose.
Reunião do Júri do Prémio António Champalimaud de Visão:
De pé, esqª para a dtª: João Silveira Botelho, Paul Sieving, Mark Bear, Joshua Sanes,
Gullapalli N Rao, António Horta Osório, José Cunha Vaz e André Valente
Sentados, esqª para a dtª: António Guterres, Leonor Beleza, Alfred Sommer e Carla Shatz
Leonor Beleza, Presidente da Fundação Champalimaud
6.2. Cerimónia de atribuição
do Prémio
Champalimaud, no dia 9 de Setembro, e foi como
Em 2011 o Prémio António Champalimaud de Visão
ministro, Pedro Passos Coelho, e outros membros do
entrou no seu terceiro ciclo. Sendo este um ano ímpar,
Governo, e ainda altas individualidades como o ex-
o Prémio destinou-se a apoiar a aplicação efectiva dos
-presidente Ramalho Eanes, deputados da Assembleia
conhecimentos no combate à cegueira nos países em
da República e do Parlamento Europeu, embaixadores
vias de desenvolvimento, justamente onde o tratamento
de muitos países com especial representatividade
e apoio clínico é mais necessário.
lusófona e também muitas personalidades de diversos
habitualmente presidida pelo Presidente da República,
Aníbal Cavaco Silva. Estiveram presentes o primeiro-
sectores da vida económica e social, membros dos
Este importante prémio tem vindo a impor-se na
órgãos da Fundação, familiares do Fundador e muitos
comunidade internacional, uma vez que em cada edição
amigos da Fundação.
estamos a receber um número crescente de candidaturas. Foram já entregues cinco prémios pela Funda-
A cerimónia foi aberta pela Presidente da Fundação,
ção, três deles reconhecendo a eficácia e a qualidade
Leonor Beleza, que expressou bem o sentimento gerado
dos cuidados clínicos prestados às populações nos
pela instituição premiada: “Gostaria que este prémio,
países em desenvolvimento, na prevenção e no trata-
agora entregue a quem fala por essas populações, a
mento da cegueira e das doenças da visão – Aravind
Eye Care System, em 2007, Helen Keller International,
em 2009, e APOC em 2011 – e os outros dois atribuídos
a organizações ou grupos que se distinguiram pelos
seus contributos excepcionais na compreensão e
valorização de descobertas científicas no campo da
visão: laboratórios dos investigadores Jeremy Nathans
e King-Wai Yau, em 2008, e de J. Anthony Movshon e
William T. Newsome, em 2010.
A cerimónia de entrega do Prémio ao African Programme for Onchocerciasis Control (APOC) decorreu no
magnífico cenário do anfiteatro exterior da Fundação
Convidados da cerimónia de entrega do Prémio António
Champalimaude de Visão , 2011
102/103
quem trabalha com elas, seja visto como um gesto de
agradeceu profundamente a generosidade deste prémio,
solidariedade de todos os Portugueses. Num momento
referindo as enormes possibilidades que se lhes abrem
como o actual, continuamos a saber olhar para o mundo
ao conseguirem assim desenvolver ainda mais oportuni-
em que vivemos e continuamos a saber reconhecer
dades de prevenção e tratamento desta doença.
e relativizar as circunstâncias concretas da vida das
pessoas e das comunidades. É em África que trabalha o
O Presidente da República, fechou a sessão ressaltando
APOC. A África está há muito, e continua, perto de nós.”
que “Todos os homens e mulheres que dedicam as
suas vidas a auxiliar os outros no combate à cegueira
Seguiram-se as intervenções de Maria Luísa Champa-
são heróis. Este Prémio é para eles, para os que nunca
limaud, filha do Fundador, em representação da família, e
desistem de lutar para garantir melhores condições de
do presidente do Júri, Prof. Alfredo Sommer.
saúde e bem-estar.”
O Prémio foi entregue pelo Senhor Presidente da Repú-
A cerimónia terminou com um magnífico momento
blica ao director do African Program for Onchocerciasis
musical, interpretado por um conjunto de guitarras e
Control (APOC), Dr. Paul-Samson Lusamba-Dikassa, que
percussão numa variação do tema hino do Prémio.
Final da cerimónia da entrega do Prémio
mês de Maio em Fort Lauderdale, nos Estados Unidos,
Sendo 2012 um ano par, o Prémio irá de novo reconhe-
o maior acontecimento mundial na área da Visão, e
cer laboratórios ou grupos que se distingam na compre-
ponto de encontro para a maioria da comunidade
ensão dos mecanismos da visão.
internacional de investigação básica e clínica nas áreas
reunindo mais de 12 500 participantes, é provavelmente
da visão e oftalmologia. A Fundação Champalimaud,
Como habitualmente, a preparação do Prémio tem início
como habitualmente, organiza, nesta ocasião, a ARVO-
no ano anterior, o que implica uma série de acções
-Champalimaud Vision Award Lecture, que já vai na
no sentido de obter nomeações e, simultaneamente,
sua quinta edição e à qual assistem membros do
a expansão da respectiva rede de “nomeadores”
Júri do Prémio António Champalimaud de Visão, bem
independentes que a Fundação tem vindo a criar e
como muitos participantes interessados nos trabalhos
consolidar através de um esforço atento e empenha-
premiados do ano precedente.
do, como um dos meios fundamentais para atrair
candidatos. No presente, esta rede é constituída por
personalidades de muito relevo no mundo da Visão,
incluindo responsáveis de departamentos científicos
de oftalmologia, ciências da visão, neurologia, neurociências e física. Contamos, também, com reitores de
escolas médicas de topo a nível mundial, e com personalidades premiadas dentro da área da oftalmologia e
especialidades afins. O alargamento desta rede tem
dado resultados muito positivos, que se concretizam
no aumento exponencial de candidaturas apresentadas
em cada edição do Prémio.
A própria Association for Research in Vision and
Ophthalmology (ARVO), que engloba cerca de 13 000
pessoas em 75 países (40% médicos oftalmologistas,
38% doutorados e 22% especialistas, incluindo optometristas, osteopatas e veterinários) e a IAPB – International
Prof. Anthony Movshon, premiado em 2010
Agency for the Prevention of Blindness, que coordena os
esforços internacionais para a prevenção da cegueira,
Alfred Sommer, presidente do Júri do Prémio, apresentou
são organizações importantíssimas a que a Fundação
os premiados de 2010, professores Anthony Movshon
se encontra associada e que muito têm contribuído para
e William T. Newsome, que expuseram as realizações
a divulgação do Prémio.
científicas pelas quais foram premiados, bem como o
seu trabalho de investigação actual, referindo as formas
A entrega de candidaturas para o Prémio António
como utilizam os montantes recebidos e a enorme
Champalimaud de Visão 2012 decorreu até 31 de
importância que este tipo de fundos tem no avanço da
Dezembro de 2011.
investigação científica.
6.4. Conferência sobre o Prémio
António Champalimaud de Visão
na ARVO
A conferência e a recepção que se segue são uma
A reunião anual da Association for Research in Vision
te científico. A ARVO tem tido um papel fundamental
and Ophthalmology (ARVO), que se realiza sempre no
na divulgação do Prémio António Champalimaud de
excelente oportunidade para o reconhecimento e celebração dos trabalhos premiados, mas também uma boa
ocasião para que isto aconteça num importante ambien-
104/105
Visão e na distribuição de informação sobre as suas
características e sobre o período de apresentação de
candidaturas.
Por outro lado, a Fundação Champalimaud tem continuado a trabalhar com a ARVO Foundation for Eye
Research (AFER) e com a própria instituição ARVO
na expansão do seu programa de acolhimento de
investigadores “Host-a-Researcher”, que agora se
denomina “Developing Country Eye Researcher Travel
Fellowships Program”, focado nos países lusófonos.
Este programa destina-se a identificar futuros cientistas
e cientistas/clínicos, nestes países, dando-lhes acesso
aos últimos desenvolvimentos e tendências na área
da investigação em visão, permitindo-lhes expandir
os seus conhecimentos e fazendo com que os
Prof. William T. Newsome, premiado em 2010
candidatos seleccionados tenham oportunidades de
encontrar outros investigadores, colegas, mentores e
líderes proeminentes, ao mesmo tempo que recolhem
informação útil para o desenvolvimento de programas de
investigação consistentes nos seus países de origem.
5.ª edicção da ARVO-Champalimaud Vision Award Lecture,
Fort Lauderdale, EUA, Maio 2011
Rede
C-Tracer
7. Rede C-TRACER
7.2. The Fourth Annual Champalimaud Research Symposium - LVPEI
Entrega da placa comemorativa do 4.º Champalimaud Research Symposium - LVPEI
ao Prof. Narsing A Rao na presença de Gullapalli N Rao, Presidente do LVPEI,
Leonor Beleza e João Silveira Botelho, Presidente e Administrador da Fundação Champalimaud
Rede C-Tracer
constitui actualmente a mais inovadora experiência em
aplicação de células estaminais a nível mundial.
O Champalimaud Translational Centre for Eye
Research (C-TRACER) é um projecto-bandeira
Nos casos de lesões graves em ambos os olhos, as
para o desenvolvimento de investigação clínica de
equipas do C-TRACER têm adoptado uma técnica em
ponta na área da visão. Foi lançado em 2008, em
que o epitélio da córnea é gerado a partir de células
parceria com o LV Prasad Eye Institute (LVPEI), sob a
epiteliais do lábio inferior do paciente. Este tipo de
liderança do Prof. Balasubramanian. As equipas do
transplante alogénico (que provém da própria pessoa) já
C-TRACER contam já com descober tas e avanços
foi aplicado com sucesso e continua a ser desenvolvido
impor tantes no tratamento com células estaminais,
neste Centro.
e em par ticular com células límbicas, sendo uma
referência mundial no desenvolvimento e aplicação
Durante 2011, as equipas C-TRACER conseguiram
clínica da técnica de transplante de epitélio límbico
avanços significativos no processo CLET, através de um
de cultura (CLET).
processo denominado SLET – Simplified Limbal Epithelial
Transplantation. Este processo consta da limpeza do
Em muitos casos de lesão grave do tecido límbico da
tecido cicatricial/pannus da parte afectada da córnea
córnea, não é possível fazer um enxerto a partir da córnea
e do seu revestimento com membrana amniótica
de dadores. Nestes casos, as equipas do C-TRACER
humana, após o que o cirurgião pulveriza partículas do
têm conseguido reconstruir a parte danificada do
tecido límbico biopsiado nessa superfície e a fecha com
olho e restaurar a visão, com o transplante de tecido
lentes de contacto. Desta forma é possível a expansão/
epitelial resultante da cultura de células estaminais
cultura in situ e in vivo das células estaminais límbicas
límbicas obtidas do tecido límbico retirado do olho bom
contidas nessas partículas. Após 10 a 14 dias o resulta-
do paciente. Este processo tem sido frequentemente
do é idêntico ao processo CLET, com a diferença de
aplicado, desde 2008, nos laboratórios C-TRACER, e
que a cultura celular é feita in vivo e não em laboratório
108/109
(ex vivo), evitando a necessidade de um laboratório de
Symposium, que decorreu no dia 30 de Janeiro. O
biologia celular.
C-TRACER tem tido um enorme desenvolvimento desde
a sua inauguração em 2008, e o simpósio anual é uma
As vantagens que o SLET oferece aos cirurgiões
ocasião privilegiada para reflectir no passado, no presente
especialistas em córnea são inúmeras, pois, ao contornar
e no futuro da investigação nesta área. Na edição
a necessidade de um laboratório de biologia celular,
de 2011 esteve presente a Presidente da Fundação
permite-lhes realizar transplantes quando não existem
Champalimaud, Leonor Beleza, que foi acolhida pelo
estas instalações. Este procedimento pode ser feito por
Presidente do LVPEI, Dr. Gullapalli N Rao, e pelo seu
qualquer cirurgião com prática no transplante de córnea
Director de investigação, Dr. D. Balasubramanian.
(queratoplastia) e pode ser realizado em zonas rurais ou
em países onde as necessidades são grandes mas os
custos do CLET não são comportáveis.
A experiência levada a cabo até à data nos laboratórios
C-TRACER demonstra que o SLET pode ser um
processo ainda melhor que o CLET, particularmente
com crianças.
Os resultados com este novo processo foram já publicados (Sangwan VS, Basu S, Macneil S, Balasubramanian
D. Simple limbal epithelial transplantation (SLET): a novel
4.º Champalimaud Research Symposium - LVPEI
Janeiro 2011
surgical technique for the treatment of unilateral limbal
stem cell deficiency. Br J Ophthalmol. 2012 Feb 10.
A quarta edição da Palestra Champalimaud foi proferida
[Epub ahead of print]).
pelo Prof. Narsing A. Rao, do Doheny Eye Institute, nos
EUA, que apresentou o tema “MicroRNA therapeutic
Em 2011 foram ainda publicados outros 16 trabalhos
intervention in amelioration of autoimmune uveitis and
sobre investigação básica e clínica desenvolvida pelas
protection of photoreceptors”. O Prof. Rao sublinhou
equipas C-TRACER.
a importância da alfa-B-cristalina, uma proteína que
está essencialmente na lente ocular, na protecção da
7.2. The Fourth Annual
Champalimaud Research
Symposium - LVPEI
integridade dos componentes da retina. Em seguida
interveio o Dr. Kanury VS Rao, do Center for Genetic
Eng. & Biotech., de Nova Deli, que sublinhou a forma
como utilizou as ferramentas dos sistemas biológicos
para identificar muitos dos potenciais fármacos que
podem ser testados para matarem o micróbio TB.
O Prof. Cunha Vaz, do Instituto AIBILI de Coimbra, onde
se instalou recentemente o C-TRACER 2, falou depois
sobre o trabalho desenvolvido pelas suas equipas na
identificação das fases de progressão da retinopatia
diabética. Seguiu-se a apresentação do Prof. Pawan
Sinha, do Department of Brain & Cognitive Sciences,
MIT, EUA, sobre o Projecto Prakash, tendo descrito a sua
A colaboração da Fundação Champalimaud com o LV
colaboração com os hospitais oftalmológicos em Deli,
Prasad Eye Institute foi celebrada em Hyderabad, na
Rajastão e Uttar Pradesh no âmbito da recuperação da
Índia, com o The Fourth Annual Champalimaud Research
visão de crianças através de intervenções cirúrgicas às
cataratas, e resumido os resultados da sua investigação
Champalimaud e a AIBILI dá apoio a áreas avançadas
sobre o desenvolvimento dos circuitos cerebrais destas
de investigação em visão que estão a ser desen-
crianças à medida que a sua visão se desenvolve e
volvidas em Coimbra e pretende alcançar significativos
melhora.
avanços em oftalmologia e outras áreas médicas relacionadas com o trabalho que o Champalimaud Centre
Para finalizar, na sua apresentação sobre “Posterior
for the Unknown está a levar a cabo.
corneal lamellar transplantation: past, present and future
directions”, o Dr. Joaquim N. Murta, dos Hospitais da
Os projectos iniciados em 2011 incluem investigação
Universidade de Coimbra, sublinhou as perspectivas e
translacional sobre doenças degenerativas relacionadas
avanços futuros nos transplantes da córnea.
com a idade e I&D na utilização de novas ferramentas
de identificação da progressão da doença. Para além
da parceria criada entre a Fundação e a AIBILI, em 2011
Em 2010, foi lançado, em Coimbra, o C-TRACER 2,
que reuniu equipas do LV Prasad Eye Institute (Índia) e
criado para promover investigação de ponta na área
da AIBILI num estudo sobre a progressão da retinopatia
da visão e lançar uma rede de centros C-TRACER a
diabética.
também foi realizado um projecto conjunto C-TRACER
nível internacional. Para a concretização deste projecto,
a Fundação Champalimaud criou uma parceria com a
No âmbito desta cooperação, realizou-se, um Simpósio
AIBILI – Associação para a Investigação Biomédica e
Champalimaud, em Coimbra. Este primeiro encontro
Inovação em Luz e Imagem, sediada em Coimbra, com
conjunto C-TRACER realizado em Portugal, que incluiu
o objectivo de desenvolver actividade de investigação e
também o parceiro do C-TRACER na Índia, o LV Prasad
colaboração em áreas ligadas à visão.
Eye Institute (LVPEI), foi um marco importante para o início
A AIBILI é o centro coordenador da Rede Europeia
desta importante colaboração, e, na medida em que
de Centros de Ensaios em Oftalmologia (EVICR.net
esta rede se for alargando, estes encontros constituirão
– European Vision Institute Clinical Research Network),
ocasiões fundamentais para troca de informação e
uma rede de centros de investigação clínica oftalmoló-
experiências entre os vários parceiros.
gica, que utiliza os mais altos padrões de qualidade,
segundo as directivas europeias e internacionais em
investigação clínica.
O trabalho já desenvolvido pela AIBILI como centro
coordenador do EVICR.net é uma garantia de como
a investigação translacional transfere os resultados da
investigação básica para a investigação clínica orientada para o paciente e vice-versa. Esta metodologia
implica o teste de novas descobertas em ambiente
clínico através da realização de cuidadosa investigação
feita em pacientes, conhecida como ensaios clínicos.
Isto inclui não só o teste de novos medicamentos, mas
também de novos métodos, ferramentas e procedimentos cirúrgicos.
Simpósio C-TRACER no AIBILI, Coimbra
Orador: Prof. Cunha Vaz
O Simpósio foi aberto pela Presidente da Fundação
Champalimaud, Leonor Beleza, que agradeceu a presen-
Este projecto suporta já várias experiências clínicas em
ça dos ilustres representantes dos Centros C-TRACER.
Portugal e tem o potencial de ser alargado para além
Seguidamente interveio o Presidente da AIBILI, Prof. Doutor
da oftalmologia a outros campos da saúde relacionados.
José Cunha Vaz, que referiu a importância da inves-
A criação da parceria C-TRACER entre a Fundação
tigação translacional e da cooperação agora acorda-
110/111
da, agradecendo a presença do Director do C-TRACER-
Índia, Prof. D. Balasubramanian, e do Professor Rubens
Belfort Jr., Professor Titular no Departamento de Oftal-
Em 2011, foi igualmente decidido alargar a rede
mologia da Universidade Federal de São Paulo,
C-TRACER para incluir o IPEPO – Instituto Paulista
Brasil, dois médicos oftalmologistas de renome inter-
de Estudos e Pesquisas em Oftalmologia, em São
nacional que durante o Simpósio apresentaram expe-
Paulo, Brasil. Este projecto é dirigido pelo Prof. Rubens
riências dentro das suas áreas de actuação, desta-
Belfort Jr. e o centro será oficialmente considerado
cando a importância da formação de redes de inter-
como C-TRACER 3 em 2012, partilhando trabalho e
câmbio, tais como aquela que a Fundação Champalimaud
experiências com os centros já existentes na Índia e
está a consolidar com a rede C-TRACER ao continuar a
em Portugal, com o objectivo de reforçar o desenvolvi-
apoiar investigação pioneira na área da visão.
mento de soluções de vanguarda na área da visão.
Outras Parcerias
8. Outras Parcerias
8.2. EARMA – European Association of Research Managers and Administrators
8.3. Centro Português de Fundações e European Foundation Centre
Fundação Champalimaud
Outras Parcerias
massificação de produtos e serviços na área do Ambient Assisted Living), o lançamento do SciPort (base de
A Fundação Champalimaud manteve a sua participação
dados da oferta científica e tecnológica no sector da
nas actividades do Health Cluster Portugal (HCP),
saúde em Portugal) e o lançamento de uma iniciativa
contribuindo para o seu objectivo de afirmar Portugal
conjunta com a AEP para o desenvolvimento do Turismo
como referência na área da saúde a nível mundial.
de Saúde, na qual a Fundação Champalimaud teve uma
participação activa.
Para além da Assembleia Geral que reuniu em 9
de Maio e em 30 de Novembro, o HCP promoveu
O aumento de 30% nas exportações do sector da
diversos eventos de networking, workshops (“Patentes
saúde em 2011 em relação ao ano anterior é um dado
e transferência de tecnologia na área da Saúde”,
excelente que pode bem ser considerado um resultado
“Investigação de translação e transferência de tecnologia
indirecto das actividades do HCP.
na área da Saúde” e “Inovação e competitividade na
investigação de translação e na investigação clínica em
Continuando a agregar “o que de melhor existe em
Portugal”), e organizou a 1.ª edição dos “Encontros com
Portugal na cadeia de valor da saúde”, o HCP conta agora
a Inovação em Saúde” sobre “Inovação nos cuidados
com 127 associados (106 em 2010) que representam
de saúde primários e na informação de saúde”, bem
mais de 70% dos doutorados a trabalhar em Portugal
como a II Conferência Anual, sob o tema “Reforço da
para o sector da saúde e, na área clínica, mais de 70% do
competitividade do cluster português da Saúde: Novos
total do volume de negócios das unidades hospitalares
paradigmas, melhores oportunidades”.
privadas.
No ano de 2011 são de destacar o início dos “projectos
A Presidente da Fundação Champalimaud, Leonor
mobilizadores” DoIT (desenvolvimento e operacionaliza-
Beleza, foi reconduzida como presidente do Conselho
ção da investigação de translação) e AAL4ALL (para
Fiscal para o triénio 2011-2014
114/115
8.2. EARMA – European
Association of Research
Managers and Administrators
8.3. Centro Português de
Fundações e European
Foundation Centre
A Fundação Champalimaud foi admitida como membro
No âmbito do Centro Português de Fundações, 2011 foi
da European Association of Research Managers and
marcado pela realização em Portugal da 22.ª Assembleia
Administrators e participou na 17.ª Conferência Anual,
Geral Anual e Conferência do European Foundation
que se realizou em Bragança entre 22 e 24 de Junho.
Centre, onde também se incluiu o 8.º Encontro de
Fundações da CPLP.
A EARMA representa os administradores e gestores
de ciência da Europa, profissionais que actuam como
Relativamente ao movimento fundacional e com impacto
interface entre a comunidade científica, as entidades
directo na Fundação Champalimaud, teve início a refor-
financiadoras e a indústria. A EARMA é um fórum
ma legislativa que conduziu à aprovação da Proposta
de discussão e de colaboração, contribuindo para a
de Lei do Censo às Fundações, publicada já a 3 de
melhoria da gestão dos projectos científicos e para a
Janeiro de 2012.
definição das políticas de ciência europeias, estando
activamente empenhada na construção da European
Research Area (ERA).
Além do espaço europeu, a EARMA tem protocolos
de colaboração com outras instituições congéneres,
nomeadamente o National Council of University Research
Administrators (NCURA).
Programa
Champimóvel
9. Programa Champimóvel
9.1. Eventos
9.2. Roteiro
9.4. Reuniões
9.5. Divulgação
9
O Champimóvel na Fundação Champalimaud
Programa Champimóvel
O projecto educativo iniciado pela Fundação Champalimaud
em 2008 e a que demos o nome de Champimóvel tem
9.1. Eventos
continuado a cumprir o seu objectivo de levar a ciência
Para além do roteiro escolar, o Champimóvel esteve
às escolas de todo o País, contribuindo para que os
presente em 23 eventos, nos seguintes locais e
estudantes do ensino secundário possam aproximar-se
instituições:
mais facilmente da ciência e despertar para a investiga-
•Parque Municipal da Covilhã
ção, envolvendo activamente alunos e professores atra-
•Vila Nova de Poiares
vés de um conjunto de actividades que vão para além
•Parque Municipal de Santa Maria da Feira
da apresentação do simulador, estendendo-se a visitas
•Baía dos Pescadores em Cascais
a instituições científicas e eventos dentro desta área, e
•Museu da Chapelaria em São João da Madeira
ainda a organização de visitas ao Centro da Fundação
•Culturalverca 2011
Champalimaud.
Com esta perspectiva criou-se em 2011 o Facebook
do Champimóvel, www.facebook.com/champimovel,
para mais fácil e atractivo acesso pelos jovens. Durante
o ano constatou-se que o site teve 100 000 visitas, o
que certamente terá contribuído para que cerca de
100 200 visitantes tenham tido a experiência do simulador Champimóvel, desde que iniciou a sua actividade
em 2008.
Visitantes do Champimóvel
118/119
O Champimóvel no Festival Optimus Alive
•Festival da Criança nos Jardins do Casino Estoril
Poiares, Pampilhosa da Serra, Mira, Montemor-o-Velho,
•Feira da Saúde e do Bem-Estar, Amadora
Vila Velha de Ródão, Abrantes, Ourém, Soure, Góis,
•Darca’11 – Associação Juvenil de Utilidade Pública
Covilhã, Oliveira do Hospital, Santa Maria da Feira,
•Noite Internacional dos Investigadores 2011 – parceria
Cascais, Setúbal, São João da Madeira, Sever do Vouga,
com a Universidade de Coimbra
Vale de Cambra, Cantanhede, Lisboa, Vila Franca de
•Festival Optimus Alive
Xira, Torres Novas, Amadora, Vila Nova de Famalicão,
•Castro Marim – férias das actividades dos tempos
Castro Marim, Ílhavo, Fundão, Belmonte, Idanha-a-Nova,
livres da área social
Sertã, Proença-a-Nova, Braga, Santo Tirso, Paços de
•Mira – Festas de São Tomé
Ferreira, Portimão, Mealhada, Anadia, Oliveira do Bairro,
•Cantanhede – Expofacic
Vagos, Aveiro, Lourinhã, Sintra, Mafra, Águeda, Estarreja,
•Ílhavo – Festival do Bacalhau
Sesimbra, Torres Vedras, Azambuja, Oeiras e Vila Real
•Portimão – Autódromo Internacional do Algarve
de Santo António), visitando 174 escolas e percor-
•Oliveira do Bairro – Festival das Sopas
rendo 8 530 km.
Em 2011 o Champimóvel esteve também no Centro de
Ciência Viva de Sintra.
Durante o ano de 2011 realizaram se 1 838 sessões,
9.2. Roteiro
perfazendo um total de 31 192 visitas, sendo 26 427
O roteiro do Champimóvel vai sendo definido em
tos/não professores.
dos visitantes crianças, 2 010 professores e 2 775 adul-
articulação com o Ministério da Educação e conforme
diversos critérios (por exemplo, integração no plano de
actividades das escolas). Fora dos períodos escolares
9.4. Reuniões
são programadas outras visitas, como aos Centros de
Em 2011 decorreram 104 reuniões preparatórias em
Ciência Viva, Câmaras Municipais, hospitais e outras
Câmaras Municipais, para receberem o Champimóvel nos
instituições, eventos esses abertos ao público.
seus municípios. Além de um membro do executivo camarário, participaram também os directores dos conselhos
O sucesso do Champimóvel também se manifesta
executivos dos respectivos agrupamentos escolares.
através de um maior número de pedidos de visita.
Durante o ano de 2011, o Champimóvel esteve em
9.5. Divulgação
seis distritos (Aveiro, Braga, Castelo Branco, Coimbra,
O roteiro e as actividades relacionadas com o
Faro e Lisboa) e percorreu 58 concelhos (Penela,
Champimóvel estão disponíveis no site da Fundação
Penacova, Miranda do Corvo, Lousã, Condeixa-a-Nova,
Champalimaud (www.fchampalimaud.org) e em www.
Figueira da Foz, Coimbra, Arganil, Tábua, Vila Nova de
parlamentoglobal.pt.
Reuniões
da Fundação
120
10. Reuniões da Fundação
10.1. Conselho de Curadores
Reunião de Curadores, Abril 2011
Da esqª para a dtª: Carlo Greco, Fernando Henrique Cardoso, Leonor Beleza,
Daniel Proença de Carvalho, Zvi Fuks e António Parreira
Reuniões da Fundação
10.1. Conselho de Curadores
novos responsáveis clínicos, Dr. Zvi Fuks, director do
Em 2011 foram realizadas três reuniões do Conselho
Centro, Prof. Doutor António Parreira, director clínico,
de Curadores, a primeira em 13 de Janeiro, para
e Prof. Doutor Carlo Greco, director de investigação
deliberação sobre a entrada de um novo membro do
clínica, ocasião em que cada um teve a oportunidade
Conselho de Administração, o Dr. António Horta Osório,
de expor as suas ideias e projectos para o Centro Clínico
e ainda a integração do Prof. Doutor António Borges
Champalimaud.
como curador, ao deixar o seu cargo na administração
da Fundação para assumir a direcção europeia do FMI.
Ambas as propostas foram aceites por unanimidade.
Seguiram-se mais duas reuniões, a segunda em 1 de
A 11 de Novembro decorreu a terceira reunião, onde foram
apresentados, entre outros temas, o desenvolvimento
do projecto do Centro de Investigação, em especial da
componente clínica.
Abril, na qual foram apresentados aos curadores os
Reunião de Curadores, Janeiro 2011
Leonor Beleza Presidente, João Silveira Botelho
e António Horta Osório, Administradores
Reunião de Curadores, Novembro 2011
Da esqª para a dtª: António Travassos, Leonor Beleza,
António Damásio, António Almeida Santos, Pedro Abreu Loureiro,
António Coutinho, Daniel Proença de Carvalho,
António Borges e João Silveira Botelho
Comunicação
e Relações Públicas
11. Comunicação e Relações Públicas
11.2. Nos média
11.3. Livro O binómio de Newton & a Vénus de Milo
124/125
Visita ao Centro de Investigação da Fundação Champalimaud
Comunicação
e Relações Públicas
a ser operacionalizada pela abertura da Clínica no
segundo semestre do ano.
A partir do final de Janeiro, a Fundação abriu as visitas
ao Centro de Investigação para grupos de pessoas
Foi particularmente gratificante para a Fundação facultar
que desde a inauguração tinham mostrado enorme
visitas a tantos grupos de estudantes, de variadas áreas,
interesse em ver as instalações e conhecer melhor as
mas bastante focalizadas em arquitectura, tecnologia
nossas actividades. Mais de 2 000 pessoas, das mais
e ciência, que daqui levaram um incentivo fortíssimo à
variadas áreas e com interesses muito diferentes, por
auto-iniciativa e um furacão de esperança em novos
aqui passaram durante o ano, quer em visitas de grupo
horizontes, que a Fundação provava ser possível
ou particulares ou ainda visitas de carácter institucional
existirem.
orientadas pela Dra. Leonor Beleza. Em todos estes
momentos, sempre sentimos uma enorme surpresa
e admiração pelo projecto arquitectónico de Charles
Correa e pela implantação dada ao edifício, nessa
fuga para o desconhecido, e, simultaneamente, forte
curiosidade e interesse pelo programa de neurociências,
testemunhado pelas reacções entusiásticas à visita aos
próprios laboratórios em plena laboração. Mas a maior
expectativa era gerada pela estratégia desenhada pela
Fundação na ligação da investigação básica à sua
aplicação clínica, nesta passagem do conhecimento
à prevenção e tratamento das doenças oncológicas,
Acolhimento dos visitantes
Público, 2 de Abril 2011
11.2. Nos média
O Champalimaud Cancer Symposium, realizado em
A Fundação Champalimaud esteve presente ao longo
mediática: a apresentação de projectos de inegável
de todo o ano de 2011 na comunicação social (digital,
interesse científico e clínico, como os avanços na área
escrita e rádio e televisão), num enquadramento
da radioterapia ou na prevenção e vigilância activa; o
estratégico orientado para o início da actividade clínica
carácter inovador da clínica do cancro da mama; o papel
e, em simultâneo, no desenvolvimento dos programas
do Centro Clínico na investigação e tratamento avançado
de investigação, muito especialmente o Programa de
do cancro; a importância e impacto nas comunidades
Neurociências e o Programa de Cancro. A progressiva
africanas de língua oficial portuguesa com a atribuição
integração da Fundação como espaço de Ciência
do Prémio António Champalimaud de Visão; os sucessos
e Cultura aberto à sociedade também foi salientada
do Champimóvel na divulgação científica aos mais
inúmeras vezes pela imprensa a propósito, por exemplo,
jovens; ou a publicação por cientistas Champalimaud
de exposições ou eventos, como o “Ar”.
de artigos científicos de grande relevância são exemplos
Janeiro, mobilizou um enorme interesse e cobertura
dos temas mais recorrentes. Neste período geraram-se
mais de 1 500 notícias positivas.
126/127
11.3. LIVRO “O binómio
de Newton & a Vénus de Milo”
Esta antologia foi compilada por Vasco Graça Moura,
A Fundação Champalimaud promoveu este ano a edição
recebido pelo seu trabalho, entre outros, o Prémio
de um livro dedicado à poesia portuguesa e à sua relação
Pessoa (1995), a Coroa de Ouro do Festival Internacional
com os temas da ciência, desde o século XVI aos dias
de Struga (2004), o Prémio Max Jacob Étranger (2007), o
de hoje. Tratando-se de dois temas tão distantes mas, ao
Prémio Nacional de Tradução italiano (2009), os Grandes
mesmo tempo, com tantos pontos de contacto, Vasco
Prémios de Poesia (1998) e de Romance e Novela
Graça Moura e Maria Bochicchio foram buscar o título
(2004) da Associação Portuguesa de Escritores, e os
desta obra a um breve poema de Álvaro de Campos,
Prémios Paulo Quintela, da Universidade de Coimbra
cujo primeiro verso parece bastante adequado na sua
(2006), e Vergílio Ferreira, da Universidade de Évora
original formulação provocatória: “O binómio de Newton
(2007), bem como por Maria Bochiccio, investigadora de
é tão belo como a Vénus de Milo…”
poesia portuguesa contemporânea, tema sobre o qual
poeta, ficcionista, ensaísta, cronista e tradutor, sendo
um dos maiores especialistas em poesia, e tendo
se debruçou na tese de doutoramento que apresentou à
A selecção de Vasco Graça Moura e Maria Bochicchio
Universidade do Porto.
resulta numa obra de referência, ricamente ilustrada
neste álbum de luxo, que se sucede a outras obras de
Foi igualmente produzida uma antologia em língua inglesa
referência, produzidas anteriormente para a Fundação
que inclui a tradução de alguns poemas originariamente
Champalimaud, como O Tratado dos Olhos de Pedro
em português, com o título A Quark for Mister Mark.
Hispano ou Os Descobrimentos Portugueses e a Ciência
Europeia, entre outras.
Livro O binómio de Newton & a Vénus de Milo
de Vasco Graça Moura e Maria Bochicchio
Biografias
128
12. Biografias
Médicos contratados em 2011
Zvi Fuks
Carlo Greco
António Parreira
Investigadores contrados em 2011
Programa Champalimaud de Neurociências
Christian Machens
Alfonso Renart
Leopoldo Petreanu
desenvolvimento da terapia de radiação modulada de
intensidade tridimensional, como uma nova modalidade
na radioterapia. Os avanços feitos nesta área representam possivelmente o nível mais alto da investigação de
translação aplicada no combate ao cancro.
O laboratório do Dr. Fuks também contribuiu de forma
decisiva para a compreensão do mecanismo que levou
ao desenvolvimento da radioterapia de dose única como
um modo único do tratamento de cancro, algo distinto
Zvi Fuks
mecanicamente da radioterapia fraccionada clássica,
Director
Champalimaud Centre for the Unknown
promover a cura do cancro humano.
que actualmente emerge com novos potenciais para
O Dr. Fuks é membro de várias sociedades profissionais:
Zvi Fuks licenciou-se em Medicina na Hebrew University-
Colégio Americano de Radiologia, Associação America-
-Hadassah Hospital, e especializou-se em Radioterapia
na da Pesquisa de Cancro, Sociedade Americana de
na Faculdade de Medicina da Universidade de Telavive.
Radiologia Terapêutica e Oncologia, Sociedade Europeia
Entre 1971 e 1976 esteve na Universidade de Stanford,
de Radiação Terapêutica e Oncológica, Sociedade de
onde a sua pesquisa se concentrou na biologia e na
Investigação Radioactiva e Presidente de programas
gestão de linfomas e cancro no ovário. Foi nomeado
de oncologia de radiação académicos. Também serviu
Professor e Presidente do Departamento de Radioterapia
no Conselho Científico do Instituto Nacional do Cancro
(1976-1984) na Hebrew University-Hadassah Hospital.
(EUA), nos Comités Consultivos Externos do Centro de
Em 1984, o Dr. Fuks juntou-se ao Departamento de
Pesquisa de Cancro da Escola Médica do Sudoeste,
Radioterapia do Centro Sloan-Kettering para o Cancro
da Universidade do Centro de Pesquisa de Cancro de
(EUA), onde serviu como Presidente (em 1984-1998 e
Chicago, MD Anderson, Centro de Cancro de Johns
2004-2005), e como Médico-Chefe do Departamento
Hopkins e Harvard Medical School.
de Planeamento do Hospital do Centro Sloan-Kettering
(1998-2004). Actualmente, é membro do Departamento
Ganhou vários prémios e distinções, entre eles a Cadeira
de Radioterapia e membro do Programa de Química e
de Alfred P. Sloan, a Medalha de Ouro no Prémio Klaas
Farmacologia Molecular no Instituto Sloan-Kettering para
Breuer, o Prémio Sir James Carreras, os Prémios de
a Pesquisa do Cancro. Foi também fundador e, por isso,
Oncologia Probstein, a Medalha de Ouro da Sociedade
é ainda Presidente do Conselho Internacional, do Centro
Americana de Radiação Terapêutica e Oncologia, o
Davidoff para o Cancro da Universidade de Telavive,
Prémio Folke Edsmyr do Instituto Karolinska na Suécia,
em Israel.
o Prémio de Excelência na Medicina do Centro Sloan-Kettering para o Cancro, o Prémio Willet F. Whitmore de
O Dr. Fuks é médico e cientista, e é reconhecido inter-
Excelência Clínica, o Prémio Honorário da Associação
nacionalmente pelas suas contribuições para os avanços
Canadiana de Oncologistas de Radiação, e a Medalha
na cura do cancro humano com radiação, muitas das
de Ouro para Hospitais de Juan A. del Regato, da
quais permanecem como padrão da prática clínica.
Universidade de Chicago. Em 2010, o Dr. Fuks foi
As suas primeiras contribuições na pesquisa clínica
admitido como membro no Instituto de Medicina das
incluem o desenvolvimento conceptual e a aplicação
Academias Nacionais. O Dr. Fuks publicou mais de 500
da irradiação de um raio de electrões na totalidade da
artigos revistos por seus pares e mais de 100 capítulos
pele com linfoma cutâneo e novas definições do papel
de livros.
da radioterapia no cancro no ovário. Mais recentemente,
os esforços clínicos do Dr. Fuks concentraram-se no
130/131
ano de 1988. Em 1989 foi recrutado como Assistente
de Pesquisa no Centro Sloan-Kettering para o Cancro,
em Nova Iorque, onde trabalhou activamente na área de
Mecanismos de Quimio-sensibilização na Radioterapia.
Certificado em Radioterapia desde 1992, tem estado
particularmente interessado no desenvolvimento de instrumentos para uma definição precisa do corpo-alvo,
baseado em técnicas de imagiologia e na prestação
de tratamentos de alta precisão.
Carlo Greco
Foi nomeado para o Instituto Europeu de Oncologia (IEO)
Director de Investigação Clínica
e do Departamento de Radioterapia
de Radioterapia até 2004. No IEO foi instrumental na
em Milão, onde serviu como Director-Adjunto da Unidade
fase de preparação das intalações de radioterapia e na
implementação da mais avançada técnica de tratamento
Carlo Greco é o regente da cadeira de Radioterapia na
do cancro através da Radioterapia Conformal em 3D
Universidade de Pisa (Itália), desde Dezembro de 2009.
(3D-CRT) Intensamente Modulada. Entre 2006 e 2009
Em Janeiro de 2010 foi também nomeado Director do
trabalhou activamente em vários projectos envolvendo o
programa da especialidade. É Professor Associado
uso da Tomografia por Emissão e Radiação de Positrões
naquela Universidade.
Informatizada para a definição do corpo-alvo, e tem feito
parte de uma equipa de investigadores que têm utilizado
Licenciou-se em Biologia na Universidade de Londres,
de forma pioneira a utilização da Radioterapia Singular
no Reino Unido (King’s College). Recebeu o seu diploma
Orientada por Imagiologia no tratamento de tumores extra-
de Medicina na Universidade de Catania, em Itália, no
-cranianos.
Consultor de Hematologia Clínica, no Hospital de Santa
Maria, em Lisboa, desde 1981-90.
Assistente de Pesquisa na Unidade de Leucemia do
Royal Postgraduate Medical School, Hammersmith
Hospital, em Londres, graças a uma bolsa patrocinada
pela Fundação Calouste Gulbenkian, 1983-85.
Professor Associado de Hematologia, na Faculdade de
Medicina da Universidade de Lisboa, 1989-1992.
Consultor de Hematologia Clínica, no Instituto Português
António Parreira
do Cancro, Lisboa, 1992.
Director Clínico
Director da Unidade de Hematologia, no Instituto
Português do Cancro, Lisboa, 1992-2004.
Formado em Medicina – Faculdade de Medicina da
Universidade de Lisboa, 1972.
Certificado em Hematologia – Faculdade de Medicina da
Universidade de Lisboa, Hospital de Santa Maria, 1979.
Doutorado em Hematologia – Faculdade de Medicina da
Universidade de Lisboa, 1989.
Cargos desempenhados:
Professor Assistente de Farmacologia, 1969-72.
Director do Departamento de Oncologia Médica, no
Instituto Português do Cancro, Lisboa, 1996-2004.
Chefe do Departamento de Hematologia, Instituto
Português de Oncologia, Lisboa, desde 2004.
Director do Instituto Português de Oncologia, Instituto
Português de Oncologia, Lisboa, 2008-2011.
Professor Associado de Medicina, Faculdade Ciências
Médicas, Universidade Nova de Lisboa, desde 1996.
Estágio em Medicina Interna, 1973-74.
Membro das seguintes Sociedades Científicas:
Efectivo de Medicina Interna, no Hospital de Santa Maria,
Sociedade das Ciências Médicas de Lisboa
em Lisboa, 1975-76.
Efectivo no Departamento de Hematologia, Hospital Henri
Mondor, em Creteil, França, patrocinado por um fundo
Sociedade Portuguesa de Hematologia
Associação Espanhola de Hematologia e Hemoterapia
granjeado pelo Governo Francês, 1977.
Sociedade Europeia de Oncologia Médica
Efectivo em Hematologia Clínica, no Hospital de Santa
Associação Europeia de Hematologia
Maria, em Lisboa, 1977-80.
Sociedade Americana de Hematologia
132/133
Programa Champalimaud de Neurociências
Christian Machens
Alfonso Renart
Christian Machens estudou Física na Univerdade de
Alfonso Renart nasceu em Madrid e em 1996 terminou
Tübingen, em SUNY, Stony Brook, e na Universidade
a sua licenciatura em Física Teórica na Universidade Autó-
de Humboldt em Berlim. Desde cedo que se interessou
noma de Madrid. Foi também na Universidade Autónoma
pela possibilidade de aplicar conceitos e métodos
de Madrid que no ano de 2000 Alfonso Renart obteve o
tradicionalmente usados em Física ao estudo do
seu grau de doutoramento, durante o qual desenvolveu
cérebro, tendo realizado a sua tese de doutoramento
modelos computacionais relacionados com memória asso-
em neurociência computacional com Andreas Herz na
ciativa e actividade neuronal persistente no laboratório
Universidade de Humboldt. Em 2002 mudou-se para
de Néstor Parga. Mudou-se depois para o laboratório
os Laboratórios de Cold Spring Harbor, nos EUA, para
de Xiao-Jing Wang na Brandeis University, Boston, EUA,
realizar o seu pós-doutoramento e onde trabalhou com
onde investigou os mecanismos neuronais responsáveis
Tony Zador e Carlos Brody. Após uma breve passagem
pela memória operacional espacial e pela capacidade de
como Investigador Independente na Ludwig-Maximilians
estimar intervalos temporais. Durante a sua estadia em
– Universidade de Munique durante o ano 2006/2007,
Boston, Alfonso passou o Verão de 2002 a aprender
foi nomeado Professor Assistente na École Normale
diferentes técnicas de electrofisiologia no curso de sistemas
Supérieure em Paris em 2007, onde se juntou ao Grupo
neurais no laboratório de Biologia Marinha, em Woodshole,
de Teoria Neuronal. Em Julho de 2011 Christian Machens
Massachusetts. Em 2004 ingressou no Instituto de
associou-se como Investigador Principal no Programa
Neurociências de Alicante como investigador Ramón y
Champalimaud de Neurociências.
Cajal. Em 2005, voltou aos Estados Unidos de América
para integrar o laboratório de Ken Harris, na Universidade
de Rutgers, convencido de que os avanços significativos na
nossa compreensão da forma como a informação é processada pelos circuitos neuronais requereriam a combinação de
métodos teóricos com a capacidade de gravar a actividade
simultânea em populações neuronais extensas. Em Rutgers,
usou registos electrofisiológicos in vivo do comportamento
de roedores e usou modelos matemáticos para estudar a
estrutura das correlações temporais nos respectivos circuitos
corticais. O seu laboratório no Champalimaud Neuroscience
Program, usará gravações de populações neuronais em
roedores despertos, modelos de redes neuronais, e ferramentas de análise de dados para pesquisar como a cognição
é moldada pela dinâmica dos circuitos neuronais.
Leopoldo Petreanu
Leopoldo Petreanu nasceu e fez os seus estudos em
Maria Luísa Vasconcelos fez o programa doutoral
Buenos Aires, Argentina, onde se licenciou em Biologia
PGDBM do Instituto Gulbenkian de Ciência, tendo
na Universidade de Buenos Aires, Argentina. Mudou-
desenvolvido a tese com o Dr. S. Lawrence Zipursky
se depois para Nova Iorque, EUA, onde obteve o seu
na Universidade da Califórnia em Los Angeles, EUA.
doutoramento na Rockefeller University, e investigou os
Estudou Dscam, uma molécula da superfície das células
mecanismos de integração de novos neurónios no bolbo
da família das imunoglobulinas que tem um papel
olfactivo. Durante o seu pós-doutoramento, Leopoldo
importante na construção dos circuitos neurais. Em
Petreanu continuou a estudar circuitos neuronais,
2004 associou-se ao Laboratório do Dr. Richard Axel
desta vez no córtex cerebral, no laboratório de Cold
na Universidade de Colúmbia, EUA, onde identificou
Spring Harbor e na Janelia Farm Research Campus,
componentes de um circuito neural que gere o compor-
nos EUA. Utilizando uma nova forma de mapeamento
tamento sexual dimorfo. Em 2008 transferiu-se para
de circuitos e métodos de imagiologia, estudou como
o Instituto Gulbenkian de Ciência, para iniciar o seu
é que a actividade do córtex cerebral é modulada por
próprio grupo de estudo focalizado em circuitos neurais
sinais eléctricos vindos de zonas distantes do cérebro.
que controlam os comportamentos inatos, tendo desde
O seu laboratório na Fundação Champalimaud conti-
então colaborado com o Programa Champalimaud de
nuará a investigar o córtex, tentando perceber como
Neurociências ao qual se junta agora.
é que diferentes áreas do cérebro coordenam a sua
actividade de modo a gerar comportamento, utilizando
para isso uma combinação de métodos de imagiologia,
fisiologia e comportamento.
Gestão do
Património
Financeiro
136/137
Nesta altura o Endowment é ainda a origem principal do
Estas ameaças manifestaram-se especialmente no
financiamento da Fundação. Há que referir que o ano
terceiro trimestre, altura em que os mercados accionistas
de 2011 foi de desafios para os mercados financeiros
globais perderam entre 12 a 22% e, embora no quarto
com inúmeras fontes de risco que afetaram o sentimento
trimestre se tenham verificado muitas recuperações,
geral de investimento e o crescimento económico em
com especial destaque para o Dow Jones Industrials
todo o mundo. Havia razões para preocupações de
que fechou em 8,4% positivo, a maioria dos mercados
fundo e a Fundação, em resposta aos riscos cada vez
accionistas acabou o ano em terreno negativo registando
mais elevados dos mercados financeiros, inverteu em
o seu segundo pior ano, com perdas de 6% no índice
devida altura a alocação dos seus activos para um perfil
global de acções a nível mundial.
mais conservador, protegendo dessa forma uma parte
substancial do seu portfolio de investimento.
Os recursos gerados na Fundação na venda de acções
foram investidos num pacote extenso de obrigações
Embora os objectivos de longo prazo da Fundação na
de rendimento elevado, que proporcionaram atractivas
gestão da sua carteira de investimentos passem pela
remunerações e reduziram a exposição à volatilidade
maximização da rentabilidade dos seus activos num
da carteira de investimento. A valores de mercado, a
quadro de diversificação para redução da volatilidade, a
Fundação Champalimaud fechou o ano com perdas
política de investimento financeiro mantém-se passiva,
de 4,4% o que fez com que o valor dos seus activos
e em 2011 com motivos reforçados, pelos inúmeros
financeiros em 31 de Dezembro se fixasse em 426.684
acontecimentos que ensombraram os mercados como a
milhares de euros. Mas note-se que a Abril de 2012
“primavera” árabe, a ameaça de abrandamento do cresci-
esta situação estava recuperada com ganhos de 5,2%
mento na China, a descida do rating dos USA e, mais
o que permitiu mais do que neutralizar as perdas de
que tudo, a ameaça da crise da dívida na Europa, onde
2011 referidas.
alguns se questionam já sobre a integridade do euro.

Relatório Anual 2011

Transcrição

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