BOLSA DE TÉCNICO DE INVESTIGAÇÃO (m/f)
Encontra-se aberto concurso para a atribuição de uma Bolsa de Técnico de Investigação no âmbito do
projecto “Unveiling the thymic interleukin 7 niche in vivo - A framework to study the cellular and
molecular control of a master regulator of T lymphopoiesis”, PTDC/SAU-IMU/110116/2009,
financiado por fundos nacionais através da FCT/MCTES (PIDDAC) e co-financiado pelo Fundo
Europeu de Desenvolvimento Regional (FEDER) através do COMPETE – Programa Operacional
Factores de Competitividade (POFC), nas seguintes condições:
Área Científica: Ciências da Saúde - Imunologia e Inflamação
Requisitos de admissão: Os candidatos devem possuir o grau de licenciatura nas áreas das Ciências da
Saúde (média superior a 15), como Bioquímica, Biologia ou afins. É dada preferência aos candidatos com
experiência prévia em técnicas de imunologia e biologia celular e molecular (citometria de fluxo,
microscopia de fluorescência, extracção de DNA e RNA, PCR).
Plano de trabalhos:
Assistência técnico-científica ao projecto.
The capacity of the immune system to respond to diverse external and internal threats (e.g. pathogens and
tumors) relies on the efficient development of a functional population of T cells. As such, a
comprehensive analysis of the factors that regulate T cell ontogeny, homeostasis and function is pivotal to
develop and optimize therapeutic strategies aimed at boosting T cell immunity. The thymus is the “cradle”
of T cell development, and provides a myriad of cytokines, chemokines and ligands for adhesion
molecules and antigen receptors that in concert instruct proper T cell development. This process is not
thymocyte-autonomous and depends on an organized tri-dimensional cellular network, collectively called
thymic stroma, composed of dendritic cells (DCs), macrophages, endothelial cells, fibroblast, and two
specialized subsets of thymic epithelial cells (TECs), cortical (cTECs) and medullary (mTECs).
Interleukin 7 (IL-7), a cytokine belonging to the common cytokine-receptor gamma-chain (Gc), is a
master regulator of T lymphopoiesis and is presumably produced by some of the aforementioned thymic
stroma components. IL-7 binds a dimeric receptor expressed in T cell precursors that consists of ligandspecific IL-7Ralpha chain and the Gc chain. Deficiency in IL-7-mediated signals in T cell progenitors,
caused by the lack of IL-7 or its corresponding functional receptors, provokes a severe defect in T cell
development in human and mice. Despite its essential role in T cell ontogeny, the identity of thymic IL-7producing cells in vivo and the underlying mechanism that controls IL-7 expression remains unresolved.
Thymic IL-7 levels are believed to change during distinct physiological settings, including aging and
immunodeficiencies, suggesting that IL-7 expression is tightly control under distinct in vivo conditions.
Recently, we provided the first temporal-spatial analysis of thymic IL-7 expressing cells in vivo, using a
novel bacterial artificial chromosome (BAC) transgenic mouse, in which a yellow fluorescent protein
(YFP) is expressed under control of IL-7 promoter (BAC.IL-7.YFP mice). We found that cells coexpressing YFP and abundant IL-7 transcripts are confined to a fraction of TECs (IL7hiTECs) detected
early during fetal development and that persist throughout post-natal life. This reporter mouse provides a
valuable tool to survey IL-7 expression in the thymus.
The development of functionally competent TECs is fundamental for thymopoiesis. Genetic defects that
block different stages of TEC differentiation cause diverse pathologies that range from immunodeficiency
(mutation in forkhead box N1, Foxn1) to autoimmunity (mutation in autoimmune regulator, Aire). The
two-prototypical TEC subsets differ not only in their anatomical location but also in their function.
Whereas cTECs are important at early stages of thymopoiesis, mTECs regulate later phases of T cell
development. It is currently accepted that both derived from a common epithelial progenitor although the
details of progenitor-product relationship are unresolved. In this regard, we documented that in the adult
thymus, IL-7hiTECs were predominantly localized at the cortico-medullary junction and displayed
features of either cTECs or mTECs, suggesting that they may constitute an intermediate progenitors of
the two mature TEC subsets. Still, many questions related to the molecular mechanism underlying the
proposed functional diversification of TECs remain unanswered. In this project, we exploit BAC.IL7.YFP mice to study (1) the development origin of IL7hiTECs in vivo and (2) the cellular and molecular
interactions that regulate thymic IL-7 expression. To accomplish these aims, a thorough phenotypic,
molecular and functional characterization of IL7hiTECs during fetal developmental and lymphopenic
conditions will be done, employing both in vivo (different stages of gestation, neonatal mice and bone
marrow chimeras using as host BAC.IL-7.YFP mice with combined deletion of RAG2 and Gc genes) and
in vitro (fetal and reaggregate thymic organ cultures, FTOC and RTOC, respectively) assays. These
experimental approaches enable us to gain insights in the timing and requirements for IL-7 expression
during thymic organogenesis, to define multiple stages and novel checkpoints in the development of
IL7hiTECs and to analyze how the interaction between TECs and distinct thymic cellular components
impact on the expression of IL-7. With a more complete understanding of the physiology of IL-7 and the
communication between TECs and thymocytes, a more rational tailored-made therapeutic approach in
immune-based pathologies can be envisage. As such, this project may provide novel insights that aid at
developing strategies to enhance thymus reconstitution and functioning in clinical contexts where more
complete T cell responses are required, including immunodeficiencies (e.g. HIV infection, bone marrow
transplantation settings) and vaccination protocols.
Legislação e regulamentação aplicável: Lei Nº. 40/2004, de 18 de Agosto (Estatuto do Bolseiro de
Investigação Científica); Regulamento da Formação Avançada e Qualificação de Recursos Humanos 2010
e Regulamento de Bolsas de Investigação Científica do IBMC aprovado pela Fundação para a Ciência e a
Tecnologia.
Local de trabalho: O trabalho será desenvolvido no grupo de “Cell Activation and Gene Expression”
(CAGE) do Instituto de Biologia Molecular e Celular - IBMC, sob a orientação científica do Doutor
Nuno Alves.
Duração da(s) bolsa(s): A bolsa terá à duração de 12 meses, com início previsto em Abril de 2011. O
contrato de bolsa poderá ser renovado até ao máximo de 33,5 meses.
Valor do subsídio de manutenção mensal: O montante da bolsa corresponde a € 745,00, conforme
tabela de valores das bolsas atribuídas directamente pela FCT, I.P. no País
(http://alfa.fct.mctes.pt/apoios/bolsas/valores) e será paga mensalmente por transferência bancária
(preferencialmente).
Métodos de selecção: A seriação dos candidatos será efectuada por avaliação curricular e entrevista aos
candidatos que cumpram todos os requisitos de admissão, com a respectiva valoração de 50%.
Composição do Júri de Selecção:
Presidente: Nuno Alves (PhD)
Vogais efectivos: Alexandra Moreira (PhD), Alexandre Carmo (PhD)
Vogal suplente: Mafalda Pinto (PhD)
Forma de publicitação/notificação dos resultados: Os resultados finais da avaliação serão
publicitados, através de lista ordenada por nota final obtida, publicada no site do IBMC, sendo o
candidato(a) aprovado(a) notificado através de e-mail.
Prazo de candidatura e forma de apresentação das candidaturas: O concurso encontra-se aberto no
período de 21 de Março e 1 de Abril de 2011.
As candidaturas devem ser formalizadas, obrigatoriamente, através de submissão electrónica de carta de
motivação
e
CV
em
http://www.ibmc.up.pt/gestaocandidaturas/index.php?codigo=PR802510.