Integrated structural Biology
Mechanisms of gene expression, from structure to drug design
Research topics in this department aim at understanding the fundamental mechanisms of gene expression into messenger RNA and into protein. Our objective is to use a bottom-up approach to investigate the different levels of spatial organization that regulate and control this biological system from the atomic level up to the complete organisms. The complexity of the regulation mechanisms require a detailed analysis of the structural organization and of the dynamics of large molecular machines implicated in transcription and translation; transcriptional activators such as nuclear hormone receptors, enzymes responsible for epigenetic histone modifications and also the architecture of chromatin in the cell nucleus. Our teams focuses particularly on the regulation cascade of nuclear hormones, from the binding of the hormone to its receptor to the recruitment of the transcription machinery in the cell nucleus. Studies on the topological modification of DNA, the integration of foreign DNA and the repair of damaged DNA contribute to a better understanding of human genome stability. Our research benefits from a pluridisciplinary environment including structural biocomputing and model building, production and characterization of biomolecules as well as structure determination tools : X ray diffraction, Nuclear Magnetic Resonance and electron microscopy.
The structural description and the dynamic properties of the biological processes are essential, not only to understand human diseases such as cancer, osteoporosis, obesity or type II diabetes, but also to conceive new pharmaceutical compounds and optimize the treatments.