Marcel Méchali - Curriculum Vitae#

Education: PhD

Position: CNRS Research Director (DRCE2 outstanding) and Laboratory head.

Institute of Human Genetics, CNRS-University of Montpellier, 141, Rue de la Cardonille, 34396 Montpellier Cedex 5, France

Scientific itinerary

• Present Position: 1998 - now CNRS Research Director (DRCE2 outstanding) and Laboratory Head, Replication and Genome Dynamics, Institute of Human Genetics
  
• 2003 - 2006 Director of the Institute of Human Genetics, CNRS, Montpellier
  
• 1984 - 1998 Laboratory Head, Laboratory of Molecular Embryology, Institut Jacques Monod, CNRS, Paris, France
  
• April 1981 - July 1984 Post-doctoral fellow at the MRC Laboratory of Molecular Biology, Cambridge, UK, in Ron Laskey-John Gurdon team

Teaching/Clinical Activities

Founder and Director of GENOPOLYS, UMS 3656 until 2016, a Life Science communication building devoted to link basic research to clinical research, industries and citizens.

Main research interest

The primary research focus is DNA replication in higher organisms and its regulation during the cell cycle and embryonic development. Most analyses employ a dynamic combination of genomic and protein methodologies, and experimental systems are Xenopus and mouse development and human and mouse ES cell cultures.

A significant contribution was to suggest that the blueprint of replication origins is intricately linked to cellular identity throughout development and differentiation. At the structural level, DNA replication origins were viewed as elements segmenting and regulating the genome in autonomous units of replication and expression. This concept reshaped our understanding of the delicate balance between cellular proliferation and differentiation and shed light on its perturbation in cancer.

At the molecular level, this research uncovered novel genetic and epigenetic facets of DNA replication origins in drosophila, mouse and human ES cells. An important discovery was an Origin-G-rich Repeated Element (OGRE) consensus, potentially forming G-quadruplexes at replication origins. This result was completely unexpected, given the AT-rich consensus sequence found at the origins of bacterial and viral DNA replication. It is now confirmed by several other investigators and by the binding to such elements of several factors involved in the initiation of DNA replication.

The chromatin environment of replication origins was also investigated, revealing a nucleosome-free region upstream of the initiation site surrounded by a regulated nucleosome spacing. Traditionally associated with developmentally regulated genes, polycomb marks were also found tightly associated with the corresponding replication origins, suggesting an intricate interplay between replication and cellular destiny.

The laboratory also discovered and characterised crucial factors involved in DNA replication during the cell cycle. They include Cdt1, the "licensing factor" responsible for controlling the initiation of DNA replication; MCM8 and MCM9, involved in DNA replication, recombination, and repair and essential for genome stability and fertility; and, more recently, Obi1, a previously unknown factor involved in replication origin activation.