Ruprecht-Karls-Universität Heidelberg
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Dobreva0119 - Scientist (f/m) / PhD position
Project no:
Dobreva0119

Project leader:

Project supervisor:
Dobreva, Gergana
Application deadline:
31. May 2019
Start of PhD project:
1. Jul 2019

Project description:

Title:
Epigenetic regulation of Cardiovascular Development and Disease
Summary:
Dynamic interactions between endothelial cells and cardiomyocytes are crucial for cardiac morphogenesis, postnatal cardiac growth, contractile performance and rhythmicity. Cardiac endothelial cells release various factors that drive cardiomyocyte proliferation, survival and contraction. Similarly, signaling from myocardial to endothelial cells is required for cardiac development and function. At a molecular level, these dynamic cell interactions induce signaling cascades, which converge to induce transcriptional and epigenetic programming that directs cardiomyocyte behavior and regulates cardiac function. Our aim is to decipher the transcriptional and epigenetic events occurring as a result of endothelial-cardiomyocyte communications. The identification of factors that regulate cardiac function in response to cell-cell signalling will help to develop novel therapeutic strategies for genetic heart diseases and regenerative approaches for heart failure
References:
• Gao R, Liang X, Cheedipudi S, Cordero J, Jiang X, Zhang Q, Caputo L, Günther S, Kuenne C, Ren Y, Bhattacharya S, Yuan X, Barreto G, Chen Y, Braun T, Evans SM, Sun Y, Dobreva G. “Pioneering function of Isl1 in epigenetic control of cardiomyocyte cell fate.” Cell Research, in press

• Singh I, Contreras A, Cordero J, Rubio K, Dobersch S, Günther S, Jeratsch S, Mehta A, Krüger M, Graumann J, Seeger W, Dobreva G, Braun T, Barreto G. “MiCEE is a ncRNA-protein complex that mediates epigenetic silencing and nucleolar organization.” Nat Genet. 2018 Jul;50(7):990-1001.

• Yuan X, Qi H, Li X, Wu F, Fang J, Bober E, Dobreva G, Zhou Y, Braun T. “Disruption of spatiotemporal hypoxic signaling causes congenital heart disease in mice.” J Clin Invest. 2017 Jun 1;127(6):2235-2248.

• Caputo L, Witzel HR, Kolovos P, Cheedipudi S, Looso M, Mylona A, van IJcken WF, Laugwitz KL, Evans SM, Braun T, Soler E, Grosveld F, Dobreva G. “The Isl1/Ldb1 Complex Orchestrates Genome-wide Chromatin Organization to Instruct Differentiation of Multipotent Cardiac Progenitors.” Cell Stem Cell 2015, 17(3):287-99

• Witzel H, Jungblut B, Choe CP, Crump JG, Braun T, Dobreva G. “The LIM protein Ajuba restricts the second heart field progenitor pool by regulating Isl1 activity” Dev Cell 2012, 23(1):58-70
Methods that will be used:
We use a wide range of biochemical, molecular/cell biological, embryological and transgenic techniques to study cardiovascular development and disease both in vitro (cell culture) and in vivo in mouse and zebrafish.
Cooperation partners:
Personal qualifications:
The applicant should possess a solid background in molecular and cell biology; specific experience in embryonic development, stem cell biology and/or epigenetics will be an advantage.
Keywords:
Epigenetics, heart development, heart disease, cellular communication