Ruprecht-Karls-Universität Heidelberg
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Nawroth0218 - Scientist (f/m) / PhD position
Project no:
Nawroth0218

Project leader:

Project supervisor:
Nawroth, Peter
Üstünel, Bilgen Ekim
Application deadline:
31. Dec 2018
Start of PhD project:
1. Feb 2019

Project description:

Title:
Mechanistic role of TSC22D4 in type 2 diabetes
Summary:
Recently we identified TSC22D4 as a novel regulator of the insulin/Akt signaling pathway and glucose metabolism in mice. Interestingly, hepatic TSC22D4 expression is upregulated by liver injury as well as during cancer cachexia. In diabetic obese mouse models, TSC22D4 promotes hyperglycemia and insulin resistance and strikingly, in obese human patients elevated hepatic TSC22D4 expression levels positively correlate with insulin resistance. Our studies clearly establish a novel connection between TSC22D4 and metabolic regulation, yet the molecular mechanisms of this connection remain elusive.
Therefore, in this project we will explore the novel functions and upstream regulators of TSC22D4 in metabolic homeostasis and we will address the open question of how exactly TSC22D4 contributes to the pathogenesis of insulin resistance and type 2 diabetes.
References:
- Ekim Ustunel, B., Friedrich, K., & Herzig, S. Control of diabetic hyperglycaemia and insulin resistance through TSC22D4. Nat Commun, 2016. 7: p. 13267. doi: 10.1038/ncomms13267

- Jones, A., K. Friedrich., & Herzig. S., TSC22D4 is a molecular output of hepatic wasting metabolism. EMBO Mol Med, 2013. 5(2): p. 294-308.

- Canterini, S., A. Bosco., & Fiorenza, M.T., Subcellular TSC22D4
localization in cerebellum granule neurons of the mouse depends on development and differentiation. Cerebellum, 2012. 11(1): p. 28-40.

- Canterini, S., V. Carletti, S., & Fiorenza, M.T., Multiple TSC22D4 iso-/phospho-glycoforms display idiosyncratic subcellular localizations and interacting protein partners. FEBS J, 2013. 280(5): p. 1320-9.
Methods that will be used:
The techniques that we will use include but are not limited to:

- Molecular Biology (PCR, Cloning, Transformation, Site-directed mutagenesis)
- Protein Biochemistry (Immunoprecipitation, Western Blotting)
- Genetic Manipulation of Mice
- Biochemical and immunohistochemical analyses of mouse and human tissues
- Immunofluorescence and Fluorescent Microscopy
Cooperation partners:
Prof. Dr. Stephan Herzig (IDC – Helmholtz Center Munich)
Prof. Dr. Peter Nawroth (Heidelberg University Hospital)
Personal qualifications:
We are looking for highly motivated and hardworking PhD students who have:

- an M.S. degree in Biochemistry, Molecular Biology, or related disciplines.
- strong analytical and critical thinking skills.
- good understanding of metabolic regulation and insulin signaling pathway
- outstanding academic record
- preferably expertise in protein-protein interactions and confocal microscopy
Keywords:
TSC22D4, insulin signaling, metabolism, insulin resistance, diabetes