Bolsa de Investigação Optimus Alive!11 Oeiras-IGC emGenética e Evolução

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Anúncio para atribuição de Bolsa de Investigação Científica no âmbito da parceria estabelecida entre o Instituto Gulbenkian de Ciência e a Everything is New, promotora do OPTIMUS ALIVE!11 OEIRAS Encontra-se aberto o concurso para atribuição de uma Bolsas de Investigação, designada por “Bolsa de Investigação Optimus Alive!11 Oeiras-IGC em Genética e Evolução” (ref:BolsaAlive-Genética e Evolução2011), no âmbito da parceria estabelecida entre o Instituto Gulbenkian de Ciência e a Everything is New, promotora do evento de música e arte OptimusAlive!Oeiras. Esta bolsa é financiada pela Everything is New, nas seguintes condições: 1. Duração e Regime de Actividade: Cada bolsa terá a duração de 12 meses a desenvolver no Instituto Gulbenkian de Ciência e no TAGC-Technological Advances for Genomics and Clinics em França, com início previsto para 1.10.2011, em regime de exclusividade, conforme regulamento de bolsas do Instituto Gulbenkian de Ciência (http://www.igc.gulbenkian.pt). 2. Objecto de Actividade: Porque razão depois de milhões de anos as infecções genómicas ancestrais ainda causam doenças? 3. Orientação Científica: Equipa de Genómica Computacional e Fisiologia Linfócitos Orientação: Jose Pereira-Leal e Jocelyne Demengeot. 4. Formação Académica: Serão admitidos para candidatura recém-licenciados (até 4 anos após licenciatura) em Biologia ou áreas afins (apenas para cidadãos Portugueses). 5. Remuneração: De acordo com a tabela de valores das Bolsas de Investigação, atribuídas pela FCT (€745.00/mês em Portugal / €1450.00/mês no estrangeiro). 6. Documentos de Candidatura: As candidaturas devem ser enviadas por correio electrónico num só documento pdf “NomeCandidato_Bolsa_Genética e Evolução.pdf”. Este documento deverá conter os seguintes elementos: Carta de Motivação, Curriculum Vitae detalhado, Cartas de referência e/ou contacto de anterior(es) orientador(es), por correio electrónico para: Maria João Leão Email: colabore@igc.gulbenkian.pt Nota: Indicar a referência da bolsa no título do email

7. Data de início e de conclusão do prazo do Concurso: De 28.06.2011 até 28.07.2011.


Descrição do Projecto (Inglês)

Title: How can an ancient genomic infection still cause diseases after millions of years? External collaboration (compulsory): Country: France Institution: TAGC-Technological Advances for Genomics and Clinics Duration : 3 months Abstract: Millions of years ago, the genomes of our ancestors were infected by a transposon (a mobile genetic element). By mechanisms still unknown, this infection was turned to the victim’s advantage and based the emergence of an “adaptive immune system”. Today, antibody diversity is generated by DNA rearrangement events, termed V(D)J recombination, mediated by RAG recombinases. The RAG enzymes are the descendents of these ancestral transposons. RAGs recognize specific sequences in the genome, termed RSS (Recombination Signal Sequences), that lie upstream of the V,D and J gene segments. RAGs catalize the random recombination of the multiple segments to generate antibody and T-cell receptor repertoires, essential for our immune system proper function. There are however sequences similar to RSSs elsewhere on the genome (cRSSs, where the c stands for cryptic), and sometimes, illegitimate recombination happens at these sites – resulting in tumorigenic translocations (Leukemias, Lymphomas). The questions we would like to address in this project are: Genome Evolution: How did the genomes of vertebrates protect themselves from the presence of these recombinases (purging RSS-like sequences from the genome, rendering them inaccessible to the RAGs by epigenetic modification, etc)? Human Disease: Can we identify potential cRSSs, and predict their recombination efficiency, in cancer genome sequences, or in human genetic variability data (SNPs)? Brief description of the experimental approach: This project will be based on bioinformatics and comparative genomics approaches. The first step of the project concentrates on the development of a bioinformatics predictor of recombination efficiency, that can predict the likelihood that any given sequence of DNA will be a substrate for RAG mediated recombination, and at which efficiency. In our groups there are experimental data on recombination efficiency on which this bioinformatics work can be based. It is in the scope of this phase that a stay at the TAGC (Marseille, France) is envisioned, in order to analyse additional datasets to maximize the predictive power of the predictor. The second step will focus on using the predictor developed to compare the genomes of organisms with and without RAGs, to identify the strategies by which genomes can cope with the presence of a recombinase. The third step will involve analyzing cancer genomes to identify RAG mediated translocations, and to analyze SNP data to assign recombinogenic potential to specific genotypes. Impact of the Study: This project addresses a fundamental evolutionary question about how organisms can cope with an infection by a mobile genetic element that causes recombination (breaking the DNA and re-joining it in different ways). This is a poorly understood event that is common in evolution, and must require some protective mechanisms. It is however for the cancer field that this project holds more promise. Illegitimate recombination is a common event in chromosomal translocations that are linked to the onset of lymphoid cancers. Being able to identify potential pathogenic RSSs in human genomes would open the possibility to develop preclinical and predictive diagnostic tools for these tumors.


Call for Application Instituto Gulbenkian de Ciência - Everything is New/OptimusAlive!11Oeiras Research Fellowships Applications are open for a Research Fellowship established under a partnership between the Instituto Gulbenkian de Ciência and Everything is New, promoters of the music and art event OptimusAlive!Oeiras. The “Optimus Alive!11 Oeiras-IGC Research fellowship inGenetics and Evolution” (ref:BolsaAlive-Genética e Evolução2011) will be financed by Everything is New under the following conditions: 1. Duration: Each Fellowship will run for 12 months, from 1.10.2011, between Portugal, at the Instituto Gulbenkian de Ciência, and TAGC-Technological Advances for Genomics and Clinics in França, on a full-time basis, according to the fellowship regulation of the Instituto Gulbenkian de Ciência (http://www.igc.gulbenkian.pt). 2. Research Topics: How can an ancient genomic infection still cause diseases after millions of years? 3. Scientific Supervision: Computational Genomics and Lymphocyte Physiology Teams; Supervision: Jose Pereira-Leal e Jocelyne Demengeot 4. Selecting Criteria: All candidates should hold a Degree in Biology or related subject, obtained within the last 4 years (only Portuguese citizens). 5. Monthly Stipend: In accordance with regulations of the FCT Scientific Fellowships in Portugal (€745.00/month in Portugal and €1450.00/ outside of Portugal). 6. Application procedure: Applications should be sent by e-mail in a unique pdf document named as follows “NomeCandidato_Bolsa_Genética e Evolução.pdf”. This document should contain a Letter of Motivation, the complete Curriculum Vitae, reference letters and/ or contacts of previous supervisors, to the following address: Maria João Leão Email: colabore@igc.gulbenkian.pt 7. Call for Applications: From 28.06.2011 until 28.06.2011.


Project Description Title: How can an ancient genomic infection still cause diseases after millions of years? External collaboration (compulsory): Country: France Institution: TAGC-Technological Advances for Genomics and Clinics Duration : 3 months Abstract: Millions of years ago, the genomes of our ancestors were infected by a transposon (a mobile genetic element). By mechanisms still unknown, this infection was turned to the victim’s advantage and based the emergence of an “adaptive immune system”. Today, antibody diversity is generated by DNA rearrangement events, termed V(D)J recombination, mediated by RAG recombinases. The RAG enzymes are the descendents of these ancestral transposons. RAGs recognize specific sequences in the genome, termed RSS (Recombination Signal Sequences), that lie upstream of the V,D and J gene segments. RAGs catalize the random recombination of the multiple segments to generate antibody and T-cell receptor repertoires, essential for our immune system proper function. There are however sequences similar to RSSs elsewhere on the genome (cRSSs, where the c stands for cryptic), and sometimes, illegitimate recombination happens at these sites – resulting in tumorigenic translocations (Leukemias, Lymphomas). The questions we would like to address in this project are: Genome Evolution: How did the genomes of vertebrates protect themselves from the presence of these recombinases (purging RSS-like sequences from the genome, rendering them inaccessible to the RAGs by epigenetic modification, etc)? Human Disease: Can we identify potential cRSSs, and predict their recombination efficiency, in cancer genome sequences, or in human genetic variability data (SNPs)? Brief description of the experimental approach: This project will be based on bioinformatics and comparative genomics approaches. The first step of the project concentrates on the development of a bioinformatics predictor of recombination efficiency, that can predict the likelihood that any given sequence of DNA will be a substrate for RAG mediated recombination, and at which efficiency. In our groups there are experimental data on recombination efficiency on which this bioinformatics work can be based. It is in the scope of this phase that a stay at the TAGC (Marseille, France) is envisioned, in order to analyse additional datasets to maximize the predictive power of the predictor. The second step will focus on using the predictor developed to compare the genomes of organisms with and without RAGs, to identify the strategies by which genomes can cope with the presence of a recombinase. The third step will involve analyzing cancer genomes to identify RAG mediated translocations, and to analyze SNP data to assign recombinogenic potential to specific genotypes. Impact of the Study: This project addresses a fundamental evolutionary question about how organisms can cope with an infection by a mobile genetic element that causes recombination (breaking the DNA and re-joining it in different ways). This is a poorly understood event that is common in evolution, and must require some protective mechanisms. It is however for the cancer field that this project holds more promise. Illegitimate recombination is a common event in chromosomal translocations that are linked to the onset of lymphoid cancers. Being able to identify potential pathogenic RSSs in human genomes would open the possibility to develop preclinical and predictive diagnostic tools for these tumors.


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