Ruprecht-Karls-Universität Heidelberg
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Korff0118 - Scientist (f/m) / PhD position
Project no:

Project leader:

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

Project description:

Impact of the transcription factor NFAT5 on vascular responses in the hypoxic lung
The lung forms a specialized border for gas exchange and may rapidly respond to local hypoxia by adapting its perfusion for optimized blood oxygenation. However, chronic hypoxia that is associated with many pulmonary diseases (e.g. fibrosis or chronic obstructive pulmonary disease, COPD) promotes irreversible structural remodeling and subsequent lung dysfunction. We observed that the transcription factor NFAT5 is expressed in vascular endothelial and smooth muscle cells of the hypoxic lung and seek to study its role in controlling structural remodeling and inflammatory responses. Specifically, the NFAT5-dependent modification of the vascular transcriptome and its impact on pulmonary resistance, blood oxygenation and activation of alveolar macrophages will be investigated.

Our work group (AG Korff) grants a professional and individual supervision of PhD students and provides a stimulating atmosphere within a team of young and enthusiastic scientists. The work program of this project allows applying 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 on international meetings. Detailed information about our group can be obtained from the institute’s website
Scherer C, Pfisterer L, Wagner AH, Hödebeck M, Cattaruzza M, Hecker M, Korff T. Arterial wall stress controls NFAT5 activity in vascular smooth muscle cells. J Am Heart Assoc. 2014 Mar 10;3(2):e000626. doi: 10.1161/JAHA.113.000626.

Hödebeck M, Scherer C, Wagner AH, Hecker M, Korff T. TonEBP/NFAT5 regulates ACTBL2 expression in biomechanically activated vascular smooth muscle cells. Front Physiol. 2014 Dec 3;5:467. doi: 10.3389/fphys.2014.00467. eCollection 2014.

Zappe M, Feldner A, Arnold C, Sticht C, Hecker M, Korff T. NFAT5 Isoform C Controls Biomechanical Stress Responses of Vascular Smooth Muscle Cells. Front Physiol. 2018 Aug 23;9:1190. doi: 10.3389/fphys.2018.01190. eCollection 2018.
Methods that will be used:
The experimental portfolio of this project includes already established multiple state-of-the-art in vitro and in vivo techniques. For instance, adenovirus-based transduction will be used to overexpress/knockout NFAT5 in cultured hypoxia-exposed endothelial and smooth muscle cells. Mouse lines allowing for cell specific inducible knockout of NFAT5 are available to study the impact of NFAT5 on lung functions in the context of hypoxia. Morphological studies will be performed based on whole mount immunofluorescence analyses in combination with confocal microscopy. To unravel the mechanisms by which NFAT5 controls cellular functions microarray and proteome profiling techniques will be applied.
Cooperation partners:
Hugo Marti (Heidelberg), Hellmut Augustin (Heidelberg), Jörg Heineke (Mannheim)
Personal qualifications:
Successful candidates should enjoy competitive and interactive teamwork within the new CRC1366 “Vascular Control of Organ Function” and the European Center for AngioScience (ECAS). They should have great interest in the life sciences, modern cell and molecular biology methods as well as physiology. Experience with animal handling (FELASA B certificate or equivalent) would be beneficial but is not mandatory for application. The PhD student should also be willing to participate in local Integrated Research Training Groups which will provide young researchers with scientific competence as well as laboratory management and communication skills.