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Epigenetic regulation of cardiac myocyte proliferation/cell cycle – from single cells to organ function - Belgium  

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Posted on : 26 August 2017

Project Description

Project

Building on our recently published findings (Thienpont, Aronsen, Robinson et al., JCI 2017), we are analysing the contribution of the epigenome in determining and maintaining the post-mitotic adult cardiac myocyte phenotype and how it can be manipulated to enhance regeneration and ameliorate disease. Given that the absence of proliferation is the Achilles’ heel of the adult myocyte, underlying the inadequate proliferation required to repair the damaged heart, identifying how cardiac myocyte fate can be reprogrammed is an exciting and clinically relevant area of research. Moreover, the absence of proliferation in the adult heart provides an ideal substrate to examine epigenetic mechanisms independent of cell cycle.

The aim of this project is to probe the role of histone methylation in the regulation ofc ardiac proliferation and in preventing/reversing deleterious hypertrophicremodelling associated with disease and ageing. This research will test the notion that manipulation of histone methylation can be employed as a tool to reprogram cardiac myocyte phenotype, and excitingly enhance proliferation required for repair.

Genomic/epigenomic analysis is performed on cardiac myocytes isolated from genetically modifiedmice (cardiac specific knockout and transgenics, adeno-associated virustransduced), mouse models of disease (aortic banding, myocardial infarction), human tissue and iPS-derived cardiac myocytes. We analyse transcriptomes andepigenomes, including methylomes of cell populations and single cells (next generation sequencing - ChIP-Seq/RNA-Seq/BS-Seq). As evidenced by our publications, we collaborate extensively within KU Leuven and outside to enhance our research.

If you are a talented scientist, with a special interest in understanding transcriptional regulation, including by the epigenome, in regulating cell fate transitions, please apply. It is also important that you wish to dig deeper than the obvious and perform important research that is relevant to human disease mechanisms.


Selected references:

Thienpont, B., J.M. Aronsen, E.L. Robinson, H. Okkenhaug, E. Loche,A. Ferrini, P. Brien, K. Alkass, A. Tomasso, A. Agrawal, O. Bergmann, I.Sjaastad, W. Reik, and H.L. Roderick. 2017. The H3K9 dimethyltransferases EHMT1/2 protect against pathological cardiac hypertrophy. J Clin Invest.127:335–348. doi:10.1172/JCI88353.


Drawnel, F.M.,D. Wachten, J.D. Molkentin, M. Maillet, J.M. Aronsen, F. Swift, I. Sjaastad, N.Liu, D. Catalucci, K. Mikoshiba, C. Hisatsune, H. Okkenhaug, S.R. Andrews, M.D.Bootman, and H.L. Roderick. 2012. Mutual antagonism between IP(3)RII and miRNA-133a regulates calcium signals and cardiac hypertrophy. J Cell Biol.199:783–798. doi:10.1083/jcb.201111095.


Higazi, D.R.,C.J. Fearnley, F.M. Drawnel, A. Talasila, E.M. Corps, O. Ritter, F. McDonald,K. Mikoshiba, M.D. Bootman, and H.L. Roderick. 2009. Endothelin-1-stimulated InsP3-induced Ca2+ release is a nexus for hypertrophic signaling in cardiac myocytes. Mol Cell. 33:472–482. doi:10.1016/j.molcel.2009.02.005.

Profile

  • You are motivated, have an enquiring mind and are excited by science.
  • You enjoy collaborating with your colleagues and externally to scientific advance.
  • You hold a Masters degree or equivalent in Bioinformatics, Bioengineering, Biomedical or Life Sciences with knowledge in relevant areas.
  • Exposure to bioinformatic analysis of next generation sequencing data and interest in R would also be an advantage.
  • You ideally have an interest in andknowledge of cell biology, physiology and cardiac biology.
  • You are a team player with excellent written and oral communication skills in English.
  • You are an independent thinker who can drive a project forward.
  • You enjoy presenting your data to collaborators and to the community at scientific meetings.
  • You perform your research to the highest standards and integrity.


Offer


  • a PhD position for 4 years.

  • a stimulating and supportive environment in which you acquire expertise as a multidisciplinary researcher.

  • Support to apply for independent funding from the Flemish Research Council (FWO).