Date : 14/09/2010

Internship proposal for : Master 1 or Master 2

Laboratory
Epigenetic and Cancer
FRE 3239 CNRS
Institut André Lwoff 7 rue Guy Moquet 94800 Villejuif
Director : Annick Harel-Bellan
Website : http://www.vjf.cnrs.fr/newial/eng/recherche/FRE2944HarelBellan.php
Main discipline : Molecular biologySystems Biology

Supervisor
Nadya Morozova
email : Cet e-mail est protégé contre les robots collecteurs de mails, votre navigateur doit accepter le Javascript pour le voir
phone : +33 33149583414

Subjects / Tools-Methodologies
1 : Network and pathway analysis/Systems Biology
2 : Bioinformatics/Computer Science
3 : Cancer Biology/Complex Systems

Summary of lab's interests

The laboratory "Epigenetic and Cancer" is affiliated to Institute Andre Lwoff, University Paris 11 and CNRS. It is located in Villejuif near Paris. The general research theme of the laboratory centers on the transcriptional- and post-transcriptional-level mechanisms controlling cell entry into proliferation versus differentiation pathways, two phenomena which are usually mutually exclusive and whose deregulation exerts a decisive effect in the process of tumorigenesis. Accordingly, one group of projects in the lab is dedicated to studies of various cancer models, aiming to elucidate the mechanisms underlying the processes of differentiation and cancerogenesis, with the strong emphasis on the epigenetic regulation of these processes. The main direction of current research is the discovery of the details and mechanisms of microRNA regulation, which is important for both differentiation and cancerogenesis. Another principal model in the lab is muscle differentiation, with the research focused on chromatin-related epigenetic aspects of differentiation control (chromatin modification, gene repositioning, etc.). The lab has extensive experience in cellular and molecular biology techniques, including siRNA technologies, which has resulted in several patent applications and led to the establishment of a Functional Genomics Platform for high-throughput screening.Currently the lab has several interdisciplinary projects, namely the mathematical modeling of microRNA action, bioinformatic analysis of the results of RNA deep sequencing, and some others. The genome wide loss-of-function screens of cancerogenic cell lines open the wide field for creating new analytical tools important for system biology of cancer.

Summary of project

The analysis of genome wide loss-of-function screens of cancerogenic cell lines open the wide opportunity for searching for new analytical and system biology tools important as for the analysis of current data resulting in the discovery of new putative treatment for the given type of cancer, so for the creation of new approach in system biology of cancer. The main assumption of the project is that the observed effect of the knockdown of the given gene is the sum of the effect in all possible pathways influencing cell proliferation and/or viability. The main outline of the project is the following: 1. Building of Integrated Protein-Protein interaction, Transcriptional and Metabolic Network. 2.Considering the shortest pathways from the given gene to all genes/proteins involved in the realization of final effect of knockdown of the given gene. 3. Calculating the specific set of rules determining the length of the pathways (in number of edges) edges, which is considerable for the given network and should be included in the next analysis. 4. Calculating the coefficient of the strength of the given pathway, depending on the strength of the given type of interaction between the nodes in it: Protein-Protein, Transcriptional or Metabolic ones). This approach can elucidate the number of the most important pathways (or new pathways) in the given specific network corresponding to the given system.