Biological systems have the inherent stability and robustness necessary to sustain the sameness defining their identities trough the transmission and expression of unaltered genetic and epigenetic information.
Genome expression, maintenance and duplication
The spatio-temporal coupling of DNA transcription, replication and repair is essential to the establishment and maintenance of both genetic/epigenetic information and cellular identity.
By combining new cutting-edge tools allowing the analysis of single molecule, single cell or individual genome, with traditional genetic and biochemical methods, the Who am I? teams will tackle the following questions: How do vertebrate cells coordinate the activation of over 105 replication origins? How, when faced with extensive DNA damage, do cells decide whether to induce DNA repair to restore viability, or to die by apoptosis? What determines which of the multiple DNA repair and tolerance mechanisms are initiated once DNA damage is sensed? How are DNA replication and repair (or transcription and replication, or transcription and repair) coupled?
Coordinating DNA replication, segregation and cell division in space and time
Coordination between genome replication and the faithful chromosome segregation to daughter cells is essential to maintaining cell identity. However, the precise molecular mechanisms coordinating DNA replication and segregation in time and space remain poorly understood. Several questions remain: how many regulators of DNA segregation remain to be discovered? How do individual components controlling these processes assemble as functional units? What are the pathways regulating their assembly in space and time? What is the molecular basis for the robustness of cell cycle control? Who am I? will combine the expertise of its teams in the field of DNA replication and cell cycle control to characterize these processes and their regulation, both at the molecular and single cell levels, but also in the context of multicellular organisms, such as D.melanogaster and C.elegans.
Genome, Epigenome and spatiotemporal regulation of gene expression
Gene expression implicates a delicate crosstalk between genome and epigenome and results from carefully orchestrated series of events involving chromatin modifications, transcription, mRNA processing, quality control and nuclear export. A strict spatio-temporal control of these mechanisms is required for a correct and regulated expression. Based on recent studies on the role of histone modifications, the labex teams will (i) dissect the crosstalk between DNA methylation and histone modifications; (ii) analyze the coordination between chromatin dynamics and mature mRNP assembly and (iii) dissect the coupling between RNA biogenesis and transport.