The Project
Genomic and functional analysis of genomic imprinting.
Winner
Dr Déborah Bourc’his
Inserm U741/Paris 7 University
Tour 43-44/2eme etage/couloir 43-44
2 place Jussieu
75251 Paris Cedex 05
France
Déborah Bourc’his, aged 34, is a research scientist at the Jacques Monod Institute in Paris, specialising in the genetic and epigenetic control of genomic imprinting and retrotransposons in mammals . She gained a PhD in human genetics at Denis Diderot University in Paris in 2000, then had a postdoctoral position at Columbia University, New York in the Department of Genetics and Development under Professor Timothy Bestor, before joining her present post in 2005.
"My work has been driven by a real passion for the biology of genomic imprinting and has been stimulated by collaborations and interactions with many leading scientists who have contributed to make the field of epigenetics fascinating. The EURYI award provides a tremendous opportunity for my team to make further advances in the understanding of genomic imprinting and its impact on human health."
Provisional Award
€ 1,217,159
Project Description
Genomic imprinting is established in mammalian gametes via the deposition of methylation marks under the control of Dnmt3L, a regulator of DNA methylation activities. These epigenetic marks are translated into a parent-specific expression of imprinted genes that have a key role on fetal development and brain functions. Because of their functional haploidy (ie expressed on just one chromosome) and their epigenetic mode of regulation, imprinted genes are particularly prone to alteration of their expression through the influence of environmental factors and assisted reproduction procedures and are commonly found involved in cancers, and congenital disorders. So far some 80 imprinted genes have been identified. However the biological function of imprinting and the complete documentation of all imprinted genes along with their phenotypic effects in mammals remains a major challenge. Bourc’his and colleagues have developed a system combining developmental and computational biology that facilitates a global approach to the biology of imprinting based on both maternal imprint-free and totally imprint-free embryos to:
Determine the net and combined effect of maternal and paternal imprinting on development by phenotypic comparison between maternal imprint-free and completely imprint-free embryos.
Extend the developmental potential of these embryos using aggregation chimeras, aiming to assess the influence of imprinting on brain functions.
Identify new imprinted genes by expression microarray analysis of Bourc’his’ imprinting deficiency models compared to wild type conceptuses, and develop a database of candidate genes for pathologies involving parental determinism.
The team’s preliminary results suggest that the number of imprinted genes could be greater than predicted and that maternal imprints play a dominant role on development. This project will give further insight into the overall biological role of imprinting and its evolutionary significance for mammals as a whole, as well as advancing our understanding of epigenetics in human health.
*Conceptus is the collective name for all products of conception including placenta, fetal membranes, as well as the fetus itself.
