Ruprecht-Karls-Universität Heidelberg
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Hecker0118 - Scientist (f/m) / PhD position
Project no:
Hecker0118

Project leader:

Project supervisor:
Hecker, Markus
Application deadline:
31. Jul 2018
Start of PhD project:
1. Sep 2018

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 take over this function as a biomechanical transducer in zyxin knockout mice. In conduit arteries a chronic rise in blood pressure increases wall tension and stretching of vascular smooth muscle cells, which respond with hypertrophy/hyperplasia and reorganization of the extracellular matrix. This project aims at elucidating the role the focal adhesions proteins zyxin and lipoma preferred partner (LPP) play in this process. 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 project is the analysis of both conventional and conditional 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 (e.g., hypertension)
• State-of-the-art non-invasive imaging methods and blood pressure recordings
• Full range of molecular biology and protein biochemistry techniques
• Immunohistochemistry, immunofluorescence, high-resolution microscopy, FACS
Cooperation partners:
• Prof. Dr. Marc Freichel, Dr. Dagmar Schumacher, 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
• Team-minded and flexible
• Ability to rapidly familiarize him/herself with new research areas in theory and praxis
Keywords: