Ruprecht-Karls-Universität Heidelberg
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Arnold_Hecker0119 - Scientist (f/m) / PhD position
Project no:
Arnold_Hecker0119

Project leader:

Project supervisor:
Arnold, Caroline
Hecker, Markus
Application deadline:
13. Jul 2019
Start of PhD project:
1. Sep 2019

Project description:

Title:
The role and regulation of arterial RGS16 during hypertension
Summary:
Hypertension or raised blood pressure is a major risk factor for cardiovascular diseases such as coronary heart disease, myocardial infarction or stroke. Thus, strategies to lower blood pressure are associated with a reduction in cardiovascular complications. Hypertension affects the arterial system by triggering the reorganization of the arterial vessel wall, i.e. vessel wall thickening. While beneficial at first, in the long term, the increase in vascular stiffness promotes hypertension even further. Vessel wall thickening is brought about by activated, i.e. proliferating and migrating, vascular smooth muscle cells (VSMCs). Thus, inhibiting VSMC activation is a promising strategy to combat the deleterious consequences of hypertension-induced arterial remodeling. In this context, G-protein activity and signalling was shown to be a limiting factor for signal transduction to orchestrate VSMC responses. However, the regulation of G-protein signalling in VSMCs is still incompletely understood. Interestingly, there is a protein family known as the “regulators of G-protein signalling” (RGS) which are endogenous inhibitors of G-protein activity. Remarkably, the members of the RGS family differ in their affinity and specificity for the different G-protein subunits which makes them highly suitable as novel drug targets.
Our previous work already identified the family member RGS5 as an important regulator of the VSMC phenotype during different types of arterial remodeling. Further, new preliminary data also points towards a promising role of RGS16 in VSMC phenotype regulation. Thus, this project aims at exploring the regulation and functional contribution of RGS16 to G-protein- and hypertension-induced VSMC responses and arterial remodeling.

Our work group (AG Arnold) grants a professional and individual supervision of PhD students in this project and provides a stimulating atmosphere within a team of young and enthusiastic scientists. The work program of this DFG-funded project comprises application of a wide range of cutting-edge techniques which guarantees a high level of scientific training. We also offer in-house methods seminars for advanced training and support participation in national and international scientific meetings. Our monthly progress reports ensure that the candidate will broaden his/her theoretical and practical knowledge and independent research skills. Detailed information about our group can be obtained from the institute’s website http://www.medizinische-fakultaet-hd.uni-heidelberg.de/index.php?id=110926&L=en

References:
Arnold C, Demirel E, Feldner A, Genové G, Zhang H, Sticht C, Wieland T, Hecker M, Heximer S, Korff T, Hypertension-evoked RhoA activity in vascular smooth muscle cells requires RGS5, FASEB J. 2018 Jan 5:fj201700384RR

Arnold C., Feldner A., Pfisterer L., Hödebeck M., Troidl K., Genové G., Wieland T., Hecker M., Korff T, RGS5 promotes arterial growth during arteriogenesis, EMBO Mol Med. 2014 Jun 27;6(8):1075-89.
doi:10.15252/emmm.201403864.
Methods that will be used:
Our experimental portfolio includes multiple established, state-of-the-art in vitro, ex vivo and in vivo techniques. Besides standard methods (qPCR, immunofluorescence imaging, confocal microscopy, Western blot, immunoprecipitation), we use vessel perfusion models, spheroid assays and 3D organoid cultures. In vivo, we utilize several surgical mouse models which allow for quantitative assessment of vascular remodeling processes such as arteriogenesis, neointima formation or hypertension-induced arterial remodeling in RGS16-deficient mice. To unravel the mechanisms by which RGS16 controls cellular functions, microarray and proteome profiling techniques will be applied.
Cooperation partners:
Nina Wettschureck (Bad Nauheim), Scott Heximer (Toronto, Canada), Thomas Wieland (Mannheim), Rudolf Schubert (Mannheim), Kirk Druey (USA)
Personal qualifications:
Successful PhD candidates should be ambitious, highly motivated and enjoy teamwork in a team of competitive young scientists. The PhD candidate should take a great interest in life sciences, molecular biology as well as physiology and be creative to apply this knowledge to develop new hypotheses. The successful candidate will be tightly supervised by the PI, should be able to work independently and also enjoy interaction and discussion with other scientists. A good background in standard molecular biological methods is expected. Experience with animal handling (FELASA B certificate or equivalent) would be beneficial but is not mandatory for application.
Keywords:
G-protein signalling, vascular smooth muscle cells, vascular remodeling, preclinical research, vascular function