Group leader, CNRS Research Director (DR2), Director of BioCampus Montpellier, Head of the MGX-Montpellier GenomiX core NGS facility
Institut de Génomique Fonctionnelle, Montpellier, France
Parental genomic imprinting is an epigenetic mechanism of gene regulation. It is understood as a mechanism aimed at controlling the amount of maternal resources allocated to the offspring from conception to weaning. Laurent Journot is performing a holistic analysis of imprinted gene function to understand the role of these genes in embryonic development, cell differentiation, and tumorigenesis.
Parental genomic imprinting restrains the expression of about 150 genes in eutherian mammals to one allele according to its parental origin. The alteration of genomic imprinting at defined loci results in different syndromes with complex phenotypes: Angelman, Beckwith-Wiedemann, Prader-Willi, Silver-Russel, and Transient Neonatal Diabetes Mellitus (TNDM). In addition, a number of imprinted genes are involved in tumor formation as oncogenes or tumor suppressor genes.
The present research on genomic imprinting is focusing on 3 main questions:
Laurent Journot and his group address the latter question, with a special emphasis on one of the imprinted genes, Zac1/Plagl1, the TNDM gene.
Imprinted genes are seemingly functionally unrelated; they do not belong to a single gene family or signaling pathway, nor do they work in an identified biological process. Accordingly, the reason for the selective targeting by genomic imprinting of a limited subset of genes with disparate molecular functions during mammalian evolution is unclear.
One current hypothesis with respect to imprinted gene function is they affect the metabolic homeostasis at the organismal level by controlling independently the metabolism of different organs including muscle, liver, pancreas, adipose tissue… The alternative hypothesis explored by Laurent Journot and his team is that imprinted genes cooperate in a single biological process that remains to be identified.
To analyze the function of imprinted genes Laurent Journot and his group combine genome-wide genomic and epigenomic techniques, in vitro cell culture, the characterization of mouse mutants, computational biology, and bio-statistics. They develop a cellular model for TNDM from human induced pluripotent stem cells and study the impact of imprinted gene mutation on normal developmental processes such as corticogenesis, adipogenesis, and pancreatic beta cell differentiation. They also study the impact of imprinted gene mutation in preclinical models of tumorigenesis.
Understanding the function of imprinted genes during normal development is crucial to identify the biological process that was targeted by parental genomic imprinting during mammalian evolution. It will also help understanding the processes that are altered in imprinted disorders and in tumors with gain or loss of imprinted gene function.
• 1981-1984, Undergraduate studies at the Ecole Normale Supérieure de Cachan, Cachan, France
• 1991, Ph.D. in Molecular Biology, University of Montpellier, France, Joël Bockaert’s Lab
• 1991-1993, Postdoctoral fellow at the Zentrum für Molekulare Biologie der Universität Heidelberg, Heidelberg, Germany, Peter H. Seeburg’s Lab.
• 1993, Appointed CNRS Staff Scientist, Centre de Pharmacologie-Endocrinologie, Montpellier, France
• 1998, Appointed CNRS Research Director, Group Leader, Institut de Génomique Fonctionnelle, Montpellier, France
• Award of the Ligue Nationale contre le Cancer, 1997
• CNRS Bronze Medal, 1995
• EMBO Fellow, 1991
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