Ruprecht-Karls-Universität Heidelberg
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Heineke0118 - Scientist (f/m) / PhD position
Project no:

Project leader:

Project supervisor:
Heineke, Jörg
Application deadline:
25. May 2018
Start of PhD project:
1. Aug 2018

Project description:

Impact of endothelial cell derived lncRNAs for cardiomyocyte signal-transduction and the cardiac stress response
We have identified a novel lncRNA, which is secreted by endothelial cells within extracellular vesicles and impacts cardiomyocyte signal-transduction. Using newly generated endothelial specific knock-out mice of this lncRNA, we will assess its functional impact on the myocardial stress response in mouse models of pathological cardiac overload. We will use proteomic and RNA sequencing methods as well as co-culture of endothelial cells and cardiomyocytes to identify and study the molecular mechanism of action of this novel lncRNA.
Malek Mohammadi M, Kattih B, Grund A, Froese N, Korf-Klingebiel M, Gigina A, Schrameck U, Rudat C, Liang Q, Kispert A, Wollert KC, Bauersachs J, Heineke J. The transcription factor GATA4 promotes myocardial regeneration in neonatal mice. EMBO Mol Med. 2017 Feb;9(2):265-279. doi: 10.15252/emmm.201606602

Appari M*, Breitbart A*, Brandes F, Szaroszyk M, Froese N, Korf-Klingebiel M, Mohammadi MM, Grund A, Scharf GM, Wang H, Zwadlo C, Fraccarollo D, Schrameck U, Nemer M, Wong GW, Katus HA, Wollert KC, Müller OJ, Bauersachs J, Heineke J. C1q-TNF-Related Protein-9 Promotes Cardiac Hypertrophy and Failure. Circ Res. 2017 Jan 6;120(1):66-77.
Methods that will be used:
Transverse aortic constriction surgery and echocardiography in mice. Isolation and primary cell culture of cardiomyocytes and endothelial cells. Calcium contractility measurements in cardiomyocytes. Immunofluorescence, FACS, Western blotting, immunoprecipitation, and standard methods in molecular biology (DNA subcloning, qPCR etc.). RNA (single cell) transcriptomics and proteomic screening methods.
Cooperation partners:
Prof. Dr. G. Dobreva, Prof. Dr. T. Wieland, Prof. Dr. S. Goerdt, Prof. Dr. H. Augustin
Personal qualifications:
Highly motivated, determined PhD student, with practical expertise in mouse work (a FELASA certificate is needed) as well as excellent practical expertise in common laboratory techniques (PCR, cloning RNA extraction, Western blotting, cell culture), good computer skills, analytical, creative thinking.
lncRNAs, intercellular communication, signal-transduction, animal models of human disease, heart failure