Ruprecht-Karls-Universität Heidelberg
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Freichel_Bading0117 - Scientist (f/m) / PhD position
Project no:

Project leader:

Project supervisor:
Freichel, Marc
Bading, Hilmar
Application deadline:
28. Feb 2018
Start of PhD project:
1. Apr 2018

Project description:

The role of nuclear calcium signals in cardiomyocytes for pathological remodeling
We showed in previous studies that Ca2+-conducting TRPC channel proteins in the plasma membrane control calcium homeostasis in cardiomyocytes under neurohumoral stimulation, and, thereby, control the activation of the hypertrophic gene program as well as pathological cardiac remodeling in vivo (Ref. 1). Transcriptional activation of the hypertrophic gene program was also shown to be dependent on a Ca2+ rise in the nucleus in isolated cardiomyocytes. However, the molecular constituents of the pathways mediating nuclear calcium rise has not been unequivocally elucidated nor the causal relationship of nuclear Ca2+ rise and the development of pathological remodeling in vivo.
1) Camacho Londoño JE, Tian Q, Hammer K, Schröder L, Camacho Londoño J, Reil JC, He T, Oberhofer M, Mannebach S, Mathar I, Philipp SE, Tabellion W, Schweda F, Dietrich A, Kaestner L, Laufs U, Birnbaumer L, Flockerzi V, Freichel M*, Lipp P*. A background Ca2+ entry pathway mediated by TRPC1/TRPC4 is critical for development of pathological cardiac remodelling. Eur Heart J 36: 2257-66, 2015 (*shared senior authorship)

2) Uhl S, Mathar I, Vennekens R, Freichel M. Adenylyl cyclase-mediated effects contribute to increased Isoprenaline-induced cardiac contractility in TRPM4-deficient mice. J Mol Cell Cadiol 74: 307-17, 2014

3) Mathar I, Kecskes M, Van der Mieren G, Jacobs G, Camacho Londoño JE, Uhl S, Flockerzi V, Voets T, Freichel M, Nilius B, Herijgers P, Vennekens R. Increased β-adrenergic
inotropy in ventricular myocardium from Trpm4-/- mice. Circ Res 114: 283-94, 2014

4) Bading H. Nuclear calcium signalling in the regulation of brain function.
Nat Rev Neurosci. 2013 Sep;14(9):593-608

5) Mauceri D, Freitag HE, Oliveira AM, Bengtson CP, Bading H. Nuclear calcium-VEGFD signaling controls maintenance of dendrite arborization necessary for memory formation.
Neuron. 2011 Jul 14;71(1):117-30
Methods that will be used:
The methods within the project will be extended as the project develops and the following list provides an overview of initial techniques that will be used.
• Cell culture models of iPS derived cardiomyocytes, neonatal and adult cardiomyocytes from mice.
• Methods to measure nuclear calcium signals and cardiomyocyte hypertrophy in vitro and in vivo
• AAV9 mediated transductions methods
• in vivo hypertrophy/remodeling models
• standard molecular biology and biochemical methods

Depending on project demands, the candidate will be involved in additional technologies, either aiming to establish them in the laboratory or developing them with external partners.
Some of the experiments will require animal work (rat and mouse models).
Cooperation partners:
Laboratories of Prof. Hilmar Bading and Professor Marc Freichel, partners of the DZHK shared expertise program or international partners
Personal qualifications:
The successful candidate should have a master’s degree in (molecular/cell) biology, molecular medicine, pharmacy or equivalent. Detailed knowledge on molecular and cell biology is expected. Ideally, the candidate has proven knowledge in cardiovascular biology and comes with a broad repertoire of basic methods in the fields of molecular and cell biology, as well as biochemistry. Previous experience in working with animal models is a plus. We expect a good command of English, a high level of motivation and the ability to design and conduct experiments independently. Furthermore, the candidate should enjoy working in an international and collaborative team.
nuclear Ca2+ signaling, cardiomyocytes, pathological cardiac remodeling