Over the past 14 years, my research has focused on molecular mechanisms underlying temporal dynamics of nucleoprotein complexes and the biological phenomena that emerge from such events. My work has revealed how dynamic protein complex assembly events can i) elicit temporal cascades of mRNA translation during early development (PhD) or ii) drive highly precise circadian transcription in the adult mouse tissues (Postdoc) and iii) lead to the establishment of dynamic chromatin states in mammalian cells and tissues (CR1, INSERM). During my PhD, I investigated biochemical mechanisms that control translation of mRNAs in Xenopus laevis. My work led to the identification of the mechanism governing one of the temporally earliest known translational events during oocyte maturation. Specifically, we discovered how RNA binding protein complexes including Pumilio, DAZL and ePAB could switch from being repressors to activators in order to initiate translational cascades in the oocyte. For my postdoctoral work, I investigated mechanisms that regulate transcription of core-clock genes in mice. The components that controlled the core circadian transcriptional oscillator were largely unknown at that time and our proteomics approach led to the identification of a sensory RACK1-PKC module that relayed information to DNA bound coreclock
transcription factors. Second, using novel transgenic mouse models, I identified a role for the PER-RNAPolII-SETX complex that controlled not only transcriptional initiation but also rhythmic transcriptional termination to establish precise circadian transcriptional cycles. More recently, I have been involved in the characterization of protein complexes that influence chromatin structure by exchanging canonical histones with non-canonical variant histone proteins. As collaborative studies, we identified the first mammalian chaperone for the histone variant H2A.Z and role for the histone variant H3.3 in governing genome stability. How these dynamic chromatin phenomena govern cellular physiology over the course of 24 hours and indeed over the lifetime of an animal remains enigmatic and is a subject that is actively being pursued currently in my laboratory.
Gratuit
Disciplines