Cyril Bourgeois PhD Molecular and Cellular Biology, INSERM Scientist

Course and current status

Since 2022 : Group leader, REGArDS team (co-head : D. Auboeuf) - LBMC, Ecole Normale Supérieure de Lyon, Lyon (France)

Since 2015 : INSERM scientist (CRCN) - Laboratory of Biology and Modeling of the Cell (LBMC) - Ecole Normale Supérieure de Lyon, Lyon (France), Didier Auboeuf's team

2011-2015 : INSERM scientist - Cancer Research Center of Lyon (CRCL), Lyon (France), Didier Auboeuf's team

2010 : HDR Sciences de la Vie, Université de Strasbourg

2009-2011 : Visiting scientist at University of Rome «Sapienza» - Institute of Molecular Biology and Pathology, Irene Bozzoni's team

2003-2008 : INSERM Scientist - IGBMC, Strasbourg-Illkirch, France, James Stevenin's team

2000-2003 : Post-doc research associate - MRC Laboratory of Molecular Biology, Cambridge (UK) and Case Western Reserve University, Cleveland OH (USA), Jon Karn's team

1994-1999 : PhD in molecular and cellular biology - IGBMC, Strasbourg-Illkirch (France), supervision: James Stevenin

Scientific summary

During my PhD, I studied the regulation of alternative splicing, focusing on the serine/arginine (SR)-rich protein family. I analysed the capacity of these proteins to activate splicing through their small RNA targeted motifs. I also characterized, in the Adenovirus E1A transcript, a splicing enhancer motif with a bidirectional activity on the upstream 3’ splice site or the downstream 5’ splice site depending on the combination of interacting SR proteins. My work paved the way for subsequent global analyses of splicing regulation and for the development of softwares aiming to predict binding of specific factors on a given RNA sequence.

During my post-doc, I studied the mechanisms controlling transcriptional elongation of HIV-1. We demonstrated how the activation of CDK9 by the viral Tat/TAR complex results in an hyper-phosphorylation of the RNA pol II carboxyl-terminal domain (CTD) and of the elongation factor Spt5, which makes the transcription complex highly processive and able to travel through pause sites.

Back to IGBMC in 2003, I worked on several projects related to splicing regulation in normal and pathological situations, accompanying the rapidly increasing number of discoveries linking alternative splicing to human pathologies (cancer and genetic diseases) and the looming perspective of splicing-based therapies.

A large part of my work consisted in studying the molecular mechanisms that control alternative splicing in the male germline during spermatogenesis, in collaboration with the group of David Elliott (University of Newcastle, UK). We studied different aspects of the function of RBMY, a chromosome Y-encoded hnRNP protein associated with male infertility, including its properties of interaction with a highly specific stem-loop RNA sequence.

Finally, through the study of the expression of SR protein SRSF2/SC35, we highlighted the complex control of expression of RNA binding proteins, that results from self- and cross-regulation loops.

Since 2009, I have been studying the regulation of alternative pre-mRNA processing in the context of cell differentiation.
My work has been focused on the functions of RNA helicases DDX5 and DDX17, which regulate gene expression patterns during differentiation through their activities at different levels: chromatin regulation, transcription, alternative splicing and biogenesis of miRNAs. More recently, our work has unveiled a link between the helicase-regulated 3D organization of genes and the transcription and co-transcriptional processing of the corresponding messenger RNAs.

Image d’exemple