Date : 08/03/2013

Laboratory

Epigenetic and Cancer
CNRS FRE 3377
CEA Saclay Bat 144
91191 Gif Sur Yvette cedex
Website
Main disciplin : Molecular Biology
Lab Director : Annick Harel-Bellan

IHES
Le Bois-Marie 35, route de Chartres
91440 Bures-sur-Yvette
Webiste
Main disciplin : Mathematics, Physics
Lab Director : Jean Pierre Bourguignon

PhD Supervisor 1
Annick Harel-Bellan
email : This e-mail address is being protected from spam bots, you need JavaScript enabled to view it
phone : +33 1 69 08 35 86

PhD Supervisor 2
Nadya Morozova
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phone : +33 1 60 92 66 96

Subjects
1 : Network and pathway analysis
2 : Bioinformatics
3 : Cancer Biology

Tools and Methodologies
1 : Systems Biology
2 : Computer Science
3 : 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.

Interdisciplinarity of project :
The analysis of data obtained in genome-wide loss-of-function screens
requiers a search for new system biology tools for network and pathways
analysis. Skills in mathematical modeling,as well as good programming and
bioinformatic skills will be important for this project.
A suggested system biology approach can be useful as for analysis of
current data obtained in the lab(on human lung adenocarcinoma), so for the
creation of new analytical tool(s) in system biology of cancer.

Do you have an available funding for this project ?
yes