PhD position. Molecular and functional analysis of cardiac diversification by cell specific genomic approaches

We are looking for a highly motivated candidate with knowledge in genetic, developmental biology, biochemistry and molecular biology. Experience in genomic approaches (ChIP-seq, RNA-seq), immuno-purification, bioinformatics and confocal microscopy would be also appreciated.

Our GReD (Genetics, Reproduction and Development) Laboratory seeks to understand the molecular and cellular mechanisms that control the formation of a eukaryotic organism from a fertilized egg. CNRS (UMR6293), INSERM (U1103) and two Universities of Clermont (University of Auvergne and Blaise Pascal University) are involved in financing 10 research teams that compose it. These teams analyze surveillance systems and repair that maintain genome integrity. They study how from an undifferentiated cell, divisions and cell differentiation lead to the formation of a harmoniously developed organism. Extending these fundamental aspects, medical approaches aimed at elucidating the genetic program of a healthy cell, identify deregulation of certain diseases, and find appropriate therapy.

Our current goal in the group is the understanding of molecular mechanisms that control the identity of heart and muscle precursors and the acquisition of morphological and functional properties during development . To investigate this we use genomic approaches: microarray, chromatin immunoprecipitation (ChIP ) and modern in vivo imaging approaches in the Drosophila model . Studies in our team have previously allowed to better understand how the heart and muscle progenitors are specified during embryonic development. An important finding was made revealing that the intrinsic and extrinsic regulators of myogenesis and early cardiogenesis were conserved between invertebrates and vertebrates. Ongoing projects aim at a better understanding of i) mechanisms of appendicular myogenesis ii ) specification of muscle stem cells in Drosophila iii ) functions of the target genes of transcription factors ladybird and their roles in migration and acquisition of cell identity iv ) morphogenesis genetic control of the formation of anterior cardiac tube v) establishing of a drosophila model of myotonic dystrophy type I.

Proposed project: The diversification of cardiac cells is accompanied by numerous changes in the expression of genes that allow cells to acquire their own identity and functions. The proposed PhD project is an integral part of a long-term project that aims to improve our understanding of the genetic pathways that control the formation of different types of cardiac cells using new technological developments involving whole genomic approaches in cell type resolution. We will therefore identify the transcriptome specific to each type of cardiac cells and the mechanisms of transcriptional regulation throughout the process of heart cells diversification. There are three main objectives in this study: i) A comparative analysis of transcription in subsets of cardiac cells ii ) A measure of the dynamics of cell – specific translation by isolating mRNA associated with ribosomes in subpopulations of cardiac cells ( TRAP method ( Heiman et al. cell, 2008) ) iii ) Sort the identified candidate and define the molecular signatures that specify different subsets of heart cells at different time windows . All experiments will be performed on Drosophila embryos. The data will then be analyzed by powerful bioinformatics tools available in the team and supplemented by functional analyzes on these candidates.

Related publications:
Jagla, T., Bidet, Y., Da Ponte, J.P., Dastugue, B., and Jagla, K. (2002). Cross-repressive interactions of identity genes are essential for proper specification of cardiac and muscular fates in Drosophila. Development 129, 1037-1047

Junion G, Bataille L, Jagla T, Da Ponte JP, Tapin R, Jagla K. 2007. Genome-wide view of cell fate specification: ladybird acts at multiple levels during diversification of muscle and heart precursors. Genes & development 21: 3163-3180

Junion G, Spivakov M, Girardot C, Braun M, Gustafson EH, Birney E, Furlong EE. 2012.
A transcription factor collective defines cardiac cell fate and reflects lineage history. Cell 148: 473-486

Contract: ANR fundings for 3 years

Contact:
Dr Guillaume Junion
Krzysztof Jagla team
GReD, INSERM U1103, CNRS UMR6293,
University of Clermont-Ferrand
28, Place Henri Dunant
63000 Clermont Ferrand
France
guillaume.junion1atudamail.fr
Tel: +33473178459

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