Ruprecht-Karls-Universität Heidelberg
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Hecker0119 - Scientist (f/m) / PhD position
Project no:
Hecker0119

Project leader:

Project supervisor:
Hecker, Markus
Application deadline:
15. Apr 2019
Start of PhD project:
1. May 2019

Project description:

Title:
Role of zyxin family members in hypertension-induced arterial remodelling
Summary:
In response to stretch or hypertension zyxin specifically translocates from the focal adhesions to the nucleus of vascular cells where it orchestrates expression of the majority of stretch-/pressure-induced genes, especially those encoding for matrix proteins and ECM-modifying enzymes. Data obtained in our group strongly indicate that other members of the zyxin family of LIM domain proteins can assume this function as a mechanotransducer in zyxin knockout mice. In (large) conduit arteries a chronic rise in blood pressure increases wall tension and stretching of vascular smooth muscle cells, which respond with hypertrophy (increase in cell size) and reorganization of the extracellular matrix. This project, which encompasses two doctoral theses, aims at elucidating the role zyxin and its closest homologue, lipoma preferred partner (LPP), play in this process. In one doctoral thesis particular focus will be on the activation and activity of these proteins and their interactions with other regulatory elements at the cell membrane, in the cytoplasm and the nucleus, and their possible mutual compensation if one of them is absent. To this end a combination of biochemical, molecular and cell biological techniques will be employed. Central part of the other thesis is the analysis of both conventional and inducible cell-specific single and double knockout mice recently generated in our group.
References:
Cattaruzza M et al., 2004;43(4):726-30.
Wójtowicz A et al., Circ Res. 2010;107(7):898-902.
Babu SS et al., Sci Signal. 2012;5(254):ra91
Ghosh S et al., J Am Heart Assoc. 2015;4(6). pii: e001712 2.
Methods that will be used:
• Primary cell culture, isolated perfused blood vessels
• CRISPR/Cas and siRNA-based knockout/knockdown
• Experimental mouse models (hypertension)
• State-of-the-art non-invasive high-resolution ultrasound and laser speckle contrast imaging methods as well as blood pressure recordings (mouse clinic)
• Full range of molecular biology and protein biochemistry techniques
• Immunohistochemistry, immunofluorescence, high-resolution confocal microscopy, TissueFAXS, FACS
Cooperation partners:
• Prof. Dr. Marc Freichel, Institute of Pharmacology, Heidelberg University
• Prof. Dr. Stefan Offermanns, Max Planck Institute for Cardiopulmonary Research, Bad Nauheim
Personal qualifications:
• Qualified master or diploma in biology, biochemistry, pharmacy or related fields
• Advanced knowledge of cell biological, molecular biological as well as biochemical techniques or high motivation to acquire the necessary skills, FELASA B certificate or equivalent
• Team-minded and flexible
• Ability to rapidly familiarize him/herself with new research areas in theory and practice
Keywords: