Cyril Bourgeois
  • E-mail :[email]
  • Phone : +33 4 72 72 86 63
  • Location : Lyon, France
Last update 2018-02-21 17:24:07.739

Cyril Bourgeois PhD Molecular and Cellular Biology, INSERM Scientist

Course and current status

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

2011-2015 : INSERM scientist at CRCL (Centre de Recherche en Cancérologie de Lyon), Centre Léon Bérard, Lyon (France), Didier Auboeuf's lab

2010 : HDR Sciences de la Vie, Université de Strasbourg

2009-2011 : Visiting scientist at the CNR (Institute of Molecular Biology and Pathology), University of Rome « Sapienza », Irene Bozzoni's lab

2003-2008 : INSERM Scientist at IGBMC (Strasbourg-Illkirch, France), James Stevenin's lab

2000-2003 : Post-doc at the MRC Laboratory of Molecular Biology (Cambridge, UK). and at Case Western Reserve University (Cleveland Ohio, USA), Jon Karn's lab

1994-1999 : PhD in molecular and cellular biology at IGBMC (Institute of Genetics and Molecular and Cellular Biology), Strasbourg-Illkirch (France), James Stevenin's lab

Scientific summary

During my PhD at IGBMC, I studied the regulation of alternative splicing, focusing mostly on the members of the serine/arginine (SR)-rich protein family. I analysed how these proteins recognize with high specificity and affinity their small RNA targets motifs, and how this translates into their capacity to activate splicing of substrates containing these 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 factors. My work paved the way for subsequent global analysis of alternative splicing regulation by those factors 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. My colleagues and I 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. We also showed that the recruitment of TFIIH to the HIV-1 promoter, along with NF-kB (which stimulates the CTD kinase activity of the CDK7 kinase of TFIIH), is a rate-limiting step in the emergence of the virus from latency.

Back to IGBMC in 2003, I worked on various projects related to splicing regulation, taking a more pathology-related turn, due to the rapidly increasing number of discoveries linking alternative splicing to human pathologies (cancer and genetic diseases) and to the looming perspective of splicing-based therapies.

A large part of my work between 2003 and 2009 consisted in studying the molecular mechanisms that control alternative splicing in the male germline during spermatogenesis. This was carried out in collaboration with the group of David Elliott (University of Newcastle, UK). In particular, we studied the function of RBMY, a chromosome Y-encoded hnRNP protein associated with male infertility. We characterised in vitro and in cellulo the interactions between human RBMY and a subset of SR proteins, and found that such interactions impaired the capacity of SR proteins to regulate specific splicing events, including germline-specific exons. We also identified the RNA targets recognised by RBMY and characterised the species-specific properties of interaction of the human RBMY protein with this highly specific stem-loop sequence.

Finally, through the study of the expression of SR protein SRSF2/SC35, a prototypical example of AS-NMD regulation (SRSF2-induced removal of terminal intron triggers nonsense-mediated RNA decay), I 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 during cell differentiation.
My work has been focusing on the functions of RNA helicases DDX5 and DDX17, which shape the gene expression programs during differentiation through their activity at different levels: chromatin regulation, transcription, alternative splicing and biogenesis of miRNAs.

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