Developmental geneticists have unraveled the transcription factors and signaling
pathways that control the formation of the cardiovascular system. These
investigations have demonstrated a clear conservation of genetic control, from
Drosophila to mammals. However, what these pathways control in terms of
downstream gene networks and how they dynamically interact to control the
diversification and the differentiation of cardiomyocytes remains largely
unknown. A detailed understanding of these processes will provide essential
insights into both normal and pathological heart development.
Drosophila is an excellent model system to study gene regulatory networks involved in cardiac organogenesis: in addition to the wealth of genetic and genomic tools available, this ?simple? genetic model organism possesses a fluid pumping heart. Our objectives are to generate and integrate genome-wide qualitative and quantitative data to dissect the Gene Regulatory Network that dynamically controls the diversification and progressive differentiation of the cardiovascular system in Drosophila. More precisely, we will:
? Generate large scale data sets by ChIP-seq and transcriptomics to describe the direct transcriptional target genes and their enhancers (cis-regulatory control elements).
? Use computational tools to integrate and analyse the newly generated datasets with pre-existing public data (coming from large scale transcriptome, proteome, and interactome screens, as well as low-throughput data documented in scientific articles and public databases).
? Establish predictive, qualitative and quantitative dynamical models of the regulatory network controlling cardioblast cell specification and differentiation.
? Exploit the genetic tools (reporter gene essays, in situ hybridization, targeted overexpression mediated gain of function, dsRNA mediated gene function knockdown...) available in Drosophila to validate and refine theses models.
? Use computational tools to evaluate the conservation of the underlying regulatory circuits from insects to mammals.
Overall, this project will contribute to building a systems-level view of Drosophila heart development and will benefit from the balanced expertise of its members..