Presentation
The research projects of the Integrative Biology and Molecular Genetics Department aim at understanding the fundamental mechanisms used by eukaryotic and prokaryotic cells to adapt to their natural environment or to a variety of stresses. The teams of the Unit try to unravel the mechanisms that control DNA damage, those that regulate gene expression, the implication of chromatin structure in epigenetic mechanisms, and the nature of the stress responses induced by oxidants or heavy metals.
Various biological model systems, chosen for their biological and experimental relevance, like the yeast Saccharomyces cerevisae, the cyanobacterium Synechocystis, the mouse or mammalian cell cultures, are studied. The research teams use a large number of experimental approaches that are either targeted (biochemistry, genetics, molecular and cellular biology…) or global (transcriptomics, proteomics, metabolomics, bio-informatics, model building…) to understand the mechanisms under study in an integrated fashion at the molecular, cellular or organismal level.
The Department is organized in five laboratories:
Laboratory of Integrative Biology (LBI)
The laboratory focuses on the multi-disciplinary analyses of the global responses of model microorganisms, cyanobacteria (mainly Synechocystis PCC6803) and yeasts (mainly Saccharomyces cerevisae) to environmental stresses triggered by oxidative agents, heavy metals, or drastic changes in nutrients availability. The genome-wide responses studied with the "omics" techniques (transcriptomics, proteomics, metabolomics and genetics) generate a wealth of experimental data that are processed, archived, integrated and represented as working models through bioinformatics and mathematics. The biological significance of the data and representative models is subsequently tested through relevant genetics, biochemical and structural analyses.
Laboratory of DNA Metabolism and Response to Genotoxics (LMARGe)
The laboratory studies various aspects of DNA metabolism such as repair, replication or the metabolism of nucleic acids. Its research activities concern the DNA surveillance mechanisms in the yeast Saccharomyces cerevisiae and in mammalian cells. Its interests also include a series of related themes such as studies about the proteasome and the analysis of DNA replication by experimental (DNA combing) and theoretical approaches (computer simulations).
Physiogenomics Laboratory (LPG)
The principal project consists in characterizing the various regions of the mouse brain by their gene expression pattern. New molecular markers have been identified. Their physiological role is currently studied by the analysis of their expression in different physio-pathological models and, using proteomics approaches, the identification of those that are secreted.
The other project aims at the molecular characterization of animal remains from the world oldest painted cave, the Chauvet Cave (Ardèche, France). The Laboratory has now sequenced the entire mitochondrial genome of the extinct cave bear (Ursus spelaeus).
Regulation of Gene Expression and Epigenetics Laboratory (LREGE)
The laboratory investigates the molecular mechanisms of gene expression and its control in eukaryotes. The function and organization of various macromolecular complexes involved in gene transcription and their regulation in stress conditions are analyzed. The organization of chromatin playing a key role in genome expression, a team investigates the epigenetic mechanisms implicated during development and differentiation, or those leading to cancer.
Oxydative Stress and Cancer Laboratory (LSOC)
The activity of the laboratory revolves around two themes. The first one bears upon cellular redox biology in S. cerevisiae and mammals. The biological impact of reactive oxygen species (ROS) is being studied through the angle of both the intrinsic toxicity of these molecules and their involvement in cellular signalling. The general aim is to establish whether and how ROS and/or cellular redox alterations contribute to the genesis of cancer and age-related diseases.
The Laboratory is interested in the mechanisms that ensure the genome stability in eukaryotes, particularly in the face of genotoxic stresses. It aims at the understanding of the mechanisms that, on the one hand, ensure the fidelity of duplication and segregation of the genome packed into chromatin and those that, on the other hand, oversee the proper progression of these processes.