About the Project
Renal stem cells form a unique population of cells that give rise to all nephrons. To ensure proper growth of the developing organ, renal stem cells need to balance pathways that promote self-renewal, proliferation and differentiation. How this delicate balance is achieved is only partially understood. The present project aims at identifying the genetic and epigenetic factors governing these fundamental decisions. We have generated several mouse models of transcription factors and epigenetic modifiers that appear to be essential for kidney development. The successful candidate will perform a detailed histological and molecular analysis of these mutant mice. In addition, he/she will carry out ChIP-Seq analysis to identify direct downstream target genes of these factors and determine how the epigenetic landscape is affected by the removal of these factors. Taken together, this research project will provide important insights into the regulation of stem cell biology, the interaction of transcription factors with the epigenetic machinery and should lead to a better understanding of congenital abnormalities of the kidney in human patients.
We are looking for a highly motivated and enthusiastic PhD student to join a well-funded team with international reputation. The ideal candidate will have a solid background in developmental biology. Experience in mouse genetics or ChIP-Seq/bioinformatics analysis are a plus.
The training will include a range of training activities including courses, meetings and workshops. Short-term internships at- and/or interactions with- the industrial partners will provide an understanding of the impact of research for the private sector. The scientific training will be further complemented by personal and career development courses (communication, research management, symposium organisation, etc.) that will provide the ESRs with essential transferable skills.
Funding Notes
This is a Marie-Curie funded position that is part of an international PhD program (RENALTRACT: http://www.ibdm.univ-mrs.fr/RENALTRACT/index.php?section=jobs). All nationalities are eligible, as long as the applicant has not spent more than 12 months in France during the last 3 years. There is no application deadline and the position will be filled as early as possible.
References
1) Schedl A. (2007) Renal abnormalities and their developmental origin. Nat Rev Genet. 8:791-802.
2) Reginensi A, Clarkson M, NeirijnckY, Lu B, Ohyama T, Groves AK, Sock E, Wegner M, Costantini F, Chaboissie MC, Schedl A (2011) SOX9 Controls Epithelial Branching by Activating RET Effector Genes during Kidney Development. Hum. Mol. Genet 20:1143-53.
3) Bandiera R, Vidal VPI, Ranc F, Clarkson M, Sahut-Barnola I, Tissier F, von Gise A, Bertherat J, Pu W, Hohenstein P, Martinez A and Schedl A. (2013) WT1 maintains adrenal-gonadal-primordium (AGP) identity and marks a novel population of AGP-like progenitors within the adult adrenal gland. Dev. Cell 27:5-18
4) Jian Motamedi F, Badro D., Clarkson MJ., Lecca MR, Bradford ST, Buske F., Saar K, Hübner N., Brändli AW, and Schedl A. (2014) WT1 Controls Antagonistic FGF and BMP-pSMAD Pathways in Early Renal Progenitors. Nature Communications doi: 10.1038/ncomms5444.
5) Lefebvre J., Clarkson M., Bradford S, Massa F., Charlet A, Lacas-Gervais S, Schulz H, Hata Y and Schedl A. Control of podocyte specific gene expression by alternatively spliced isoforms of WT1. Kidney International in press.
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