Denis Duboule's scientific contributions concern the molecular genetics of vertebrate development, with interfaces in medical genetics, evolutionary biology and transcription regulation. His latest work focuses on the Hoxgene family , a series of transcription factors of high heuristic value, in particular concerning their regulatory strategies, functional organization and role in morphological evolution.
This year's lecture will focus on recent developments in the regulation of developmental genes, particularly at large distances and using the latest technologies such as high-throughput approaches and deep learning to identify and characterize regulatory sequences (enhancers) and understand their operating logic.
During animal development, genes must be switched on (and off) at extremely precise times and in particular cell types. How can this choreography be set up, what signals are involved and how do they act, who gives the " orders " to such and such genes to produce their RNAs from which the proteins will be coded ? Much of this information is transmitted via DNA sequences located in the vicinity of the genes in question, which are capable of transferring this information and thus controlling gene activity. These sequences, known as enhancers , were discovered in the 1980s. More recent developments in high-throughput technologies will revitalize these studies and lead to remarkable discoveries, in particular concerning the " logics " of action of these sequences, either isolated or in groups. After a general introduction, this year's lecture will present some of these advances, relating for example to pathological states induced by genetic problems in these sequences (enhanceropathies), or to the emerging role of transposable elements, or to the use of artificial intelligence to establish and use the grammars, i.e., the internal logic of the DNA sequences that make up these enhancers.