Ruprecht-Karls-Universität Heidelberg
HBIGS homepage | Forgot password
SFB 1158_Kuner_Agarwal0119 - Scientist (f/m) / PhD position
Project no:
SFB 1158_Kuner_Agarwal0119

Project leader:

Project supervisor:
Kuner, Rohini
Application deadline:
15. Aug 2019
Start of PhD project:
1. Oct 2019

Project description:

Title:
Functional roles and mechanisms of post-translation modification in diabetic neuropathy
Summary:
Post-translational modifications (PTM) constitute a key mode of regulation of protein function and localization in biological processes. Post-translational covalent modification is an important regulator of the functional properties of many proteins and is emerging as a prominent regulatory mechanism in the pathophysiology of a variety of disorders, including cancer, diabetes and a wide range of neurodegenerative diseases. Diabetes is manifest with an increase in the levels of ROS, methylglyoxal (MG) and glyoxal (GL). ROS, produced during metabolic stress, hyperglycemia, etc., directly regulates post-translation of target proteins. In this project, we aim to investigate the changes in proteomes and alteration in PTM of proteins in Schwann cells and peripheral neurons at different diabetic stages to understand the modulation of axonopathy by Schwann cell dysfunction in progression of Diabetic peripheral neuropathy (DPN). You will identify and characterize the novel metabolic target(s) of PTM and their impact on the metabolic pathways.
References:
1. Rojas DR, Kuner R, Agarwal N. Metabolomic signature of type 1 diabetes-induced sensory loss and nerve damage in diabetic neuropathy. J Mol Med (Berl). 2019 Jun;97(6):845-854.

2. Agarwal N, Helmstädter J, Rojas DR, Bali KK, Gangadharan V, Kuner R. Evoked hypoalgesia is accompanied by tonic pain and immune cell infiltration in the dorsal root ganglia at late stages of diabetic neuropathy in mice. Mol Pain. 2018 Jan-Dec;14

3. Rojas DR, Tegeder I, Kuner R, Agarwal N. Hypoxia-inducible factor 1α protects peripheral sensory neurons from diabetic peripheral neuropathy by suppressing accumulation of reactive oxygen species. J Mol Med (Berl). 2018 Dec;96(12):1395-1405.

4. Njoo C, Agarwal N, Lutz B, Kuner R. The Cannabinoid Receptor CB1 Interacts with the WAVE1 Complex and Plays a Role in Actin Dynamics and Structural Plasticity in Neurons. PLoS Biol. 2015 Oct 23;13(10)

5. Simonetti M, Agarwal N, Stösser S, Bali KK, Karaulanov E, Kamble R, Pospisilova B, Kurejova M, Birchmeier W, Niehrs C, Heppenstall P, Kuner R. Wnt-Fzd signaling sensitizes peripheral sensory neurons via distinct noncanonical pathways. Neuron. 2014 Jul 2;83(1):104-21.
Methods that will be used:
Standard molecular biology techniques, protein biochemistry, quantitative fluorescence microscopy, Generation of conditional tissue-specific mutant mice using Cre/lox P system, rodent behavioral assay for DPN, advance in vitro methods to study neuronal and Schwann cell interactions.
Cooperation partners:
We are collaborating extensively locally (SFB 1118, COS, SFB1158 and Uni HD) and internally and expect that applicant engage in interdisciplinary exchange and is open to collaboration partners.
Personal qualifications:
It is expected that the applicant should be highly motivated to conduct challenging and internationally competitive research at the interface of biochemistry, molecular biology and behavioral studies. Experience in biochemistry, molecular biology and animal handling is preferred.
Keywords:
Biochemistry, Molecular biology, Rodent behavioral studies, Diabetes, cellular communications