Ruprecht-Karls-Universität Heidelberg
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Kroll0118 - Scientist (f/m) / PhD position
Project no:
Kroll0118

Project leader:

Project supervisor:
Kroll, Jens
Application deadline:
30. Sep 2018
Start of PhD project:
1. Jan 2019

Project description:

Title:
The function of the Rac1 regulator ELMO1 in the vasculature and in renal development under high glucose in zebrafish and in human diabetic nephropathy
Summary:
Glucose-induced microangiopathy and nephropathy are diabetes-associated diseases. The Rac1 regulator ELMO1 is an important regulator of vascular development in zebrafish and polymorphisms in different regions of the human ELMO1 gene are associated with diabetes-associated nephropathy. The aim of this project is to analyze ELMO1’s function in the development of glucose-associated pathophysiological disorders in zebrafish and in diabetic patients. The project will include expression analyses in zebrafish and in diabetic patient samples; loss-of-function and gain-of-function experiments in zebrafish and biochemical studies in vitro.
References:
1. She J, Yuan Z, Wu Y, Chen J, Kroll J (2018). Targeting erythropoietin protects against proteinuria in type 2 diabetic patients and in zebrafish. Mol Metab. doi: 10.1016/j.molmet.2017.11.006.

2. Wiggenhauser LM, Kohl K, Dietrich N, Hammes HP, Kroll J (2017). Studying diabetes through the eyes of a fish: Microdissection, visualization and analysis of the adult tg(fli:EGFP) zebrafish retinal vasculature. J Vis Exp. doi: 10.3791/56674.

3. Schaeker K, Bartsch S, Patry C, Cramer-Stoll S, Hillebrands JL, Wieland T, Kroll J (2015) The bipartite Rac1 guanine nucleotide exchange factor engulfment and cell motility 1/dedicator of cytokinesis 180 (Elmo1/Dock180) protects endothelial cells from apoptosis in blood vessel development. J Biol Chem 290: 6408- 6418.

4. Jörgens K, Stoll SJ, Pohl J, Fleming TH, Sticht C, Nawroth PP, Hammes HP, Kroll J (2015) High tissue glucose alters intersomitic blood vessels in zebrafish via methylglyoxal targeting the VEGF receptor signalling cascade. Diabetes 64(1):213-2.

5. Epting D, Wendik B, Bennewitz K, Dietz CT, Driever W, and Kroll J (2010) The Rac1 regulator ELMO1 controls vascular morphogenesis in zebrafish. Circ Res. 107: 45-55.
Methods that will be used:
CRISPR/CAS mutagenesis, imaging, organ analysis, metabolome analysis, endothelial cell signalling, expression studies, gene analysis, zebrafish
Cooperation partners:
Prof. Dr. Hans-Peter Hammes, Prof. Dr. Peter Nawroth
Personal qualifications:
Master in live science, great interest and enthusiasm for science
Keywords:
metabolism, endothelial signalling, diabetic complications, zebrafish