Working on mechanisms of RNA degradation related with mRNA translation and the assembly of RNA-protein complexes. Developing both large scale quantitative biochemical and genetic approaches in S. cerevisiae and the tools for the integration of the obtained results with functional genomics data.
Medical Degree (1996), Cluj, Romania – scientific report on a method for multiple substrate enzyme kinetics parameter estimation.
PhD in biochemistry (2001) supervised by Mircea Cucuianu, Cluj, Romania, on the characterisation of proteins through complex purification and mass-spectrometry identification.
Habilitation for PhD supervising, HDR (2010) Paris Diderot University.
Silver medal at the 22nd International Chemistry Olympiad (1990)
Thérèse Lebrasseur prize (2019)
RIBOSOME BIOGENESIS OCCURS THROUGH ORDERED ASSEMBLY OF DOZENS OF PROTEINS
My work on ribosome biogenesis started by with one of the first purification of precursors to the 60S ribosomal subunit, the identification of new factors (EMBO J, 2001) and the first demonstration of an assembly order in this highly complex and conserved pathway (Mol Cell Biol 2003). To establish in which order the 120 factors involved in the formation of 60S ribosomal subunits assemble, I pioneered the use of quantitative mass- spectrometry and combinations of mutants for the study of large complexes assembly (Nucl Acids Res, 2008, 2013).
NUCLEAR RNA DEGRADATION REQUIRES POLY-ADENYLATION AND SPECIFIC FACTORS
Among the different factors and interactions that I discovered in collaborative projects, an important one involved the purification of a complex that is required for the poly-adenylation and degradation of defective transcription products in the nucleus of eucaryotic cells (Cell, 2005, collaboration with D. Tollervey) and the identification of other involved factors (Mol Cell Biol, 2008).
GENETIC INTERACTION PROFILES ARE THE BEST PREDICTORS OF GENE FUNCTION
In search for new ways to explore gene function, I participated to the development of a method that allows to measure on a large scale the impact on growth of introducing mutants of two different genes in the same strain (Genetic Interactions Mapping, GIM). The best predictor for an unknown gene function can be found by correlating the profiles of sensitivity of mutants to a range of perturbations (PNAS, 2008). A larger scale genome-wide set of screens that I coordinated, led to results that identified, for example, a new ribosome-associated complex involved in aberrant protein degradation (PNAS, 2013, collaboration with M. Fromont-Racine) and new genes involved in RNA transport, maturation and degradation (manuscript in preparation).
Funded by young investigator ANR-08-JCJC0019-01, GENO-GIM (2008-2012)
TRANSLATION-DEPENDENT mRNA DEGRADATION IN YEAST INVOLVES UNEXPLORED MECHANISMS AND SUBSTRATES
I coordinated the generation of a collection of 900 yeast strains in which a long 3′ untranslated region (UTR) replaced the normal UTR, in an attempt to destabilize the mRNA. Initially to be used as a tool to systematically explore the function of essential genes, the collection turned out to be valuable to identify the importance of the translated region length in mRNA stability (Cell Rep, 2014). Work in collaboration with my colleagues showed that the involved degradation mechanism, called NMD, for nonsense-mediated mRNA decay, affects a massive number of transcripts, generated from about half of yeast genes. These abortive transcripts result from an intrinsic inability of RNA polymerase II to precisely start transcription (eLife, 2015).
How exactly NMD substrates are degraded cannot be discovered without highly sensitive biochemical assays. We performed a large number of systematic analyses of NMD complexes and discovered two mutually exclusive macromolecular assemblies required for this degradation pathway (EMBOJ, 2018). How these assemblies form and how their activity is regulated are currently under investigation.
The main project on NMD and RNA degradation pathways funded through ANR: CleaNMD, ANR-14-CE10-0014, 2014-2018, and DEFineNMD, ANR-18-CE11-0003, 2019-2023.
We benefit from support from the French Ministry of higher education, research and innovation and from the “Fondation ARC pour la recherche sur le cancer“. Our laboratory is affiliated to the “Complexité du Vivant” doctoral school, Sorbonne University.