Ruprecht-Karls-Universität Heidelberg
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Mayer0219 - Scientist (f/m) / PhD position
Project no:

Project leader:

Project supervisor:
Mayer, Matthias
Application deadline:
30. Jun 2019
Start of PhD project:
1. Jul 2019

Project description:

Structure-function analysis of J-domain cochaperones
In the center of this PhD project is the molecular mechanism of the Hsp70 chaperone machinery. Hsp70 chaperones are central hubs of the protein quality control network and work in collaboration with J-domain cochaperones and nucleotide exchange factors to facilitate a wide variety of protein folding processes and so (re)establish protein homeostasis. The Hsp70s are highly dynamic nanomachines that modulate the conformation of their substrate polypeptides by transiently binding to short, mostly hydrophobic stretches. This interaction is regulated by an intricate allosteric mechanism. The J-domain cochaperones target Hsp70 to their polypeptide substrates, and the nucleotide exchange factors regulate the lifetime of the Hsp70-substrate complexes. In vivo, Hsp70 and J-domain cochaperones are modified by posttranslational modifications and the aim of this PhD project will be to analyze the effect of posttranslational modifications in J-domain proteins in vitro using biochemical and biophysical techniques with purified proteins. Complementary in-vivo-experiments will be carried out in mammalian cell culture. This PhD project is a collaborative project between our group in Heidelberg and the group of Nadinath Nillegoda in Australia and the successful PhD student will start in Heidelberg and finish her/his PhD in Heidelberg but will also spend two years in Australia at Monash University.
Mayer, M. P. & Gierasch, L. M. Recent advances in the structural and mechanistic aspects of Hsp70 molecular chaperones. Journal of Biological Chemistry jbc.REV118.002810 (2018). doi:10.1074/jbc.REV118.002810

Kityk, R., Kopp, J. & Mayer, M. P. Molecular Mechanism of J-Domain-Triggered ATP Hydrolysis by Hsp70 Chaperones. Molecular Cell 69, 227–237.e4 (2018).

Kityk, R., Vogel, M., Schlecht, R., Bukau, B. & Mayer, M. P. Pathways of allosteric regulation in Hsp70 chaperones. Nat Commun 6, 8308 (2015).

Mayer, M. P. Hsp70 chaperone dynamics and molecular mechanism. Trends in Biochemical Sciences 38, 507–514 (2013).
Methods that will be used:
Protein purification methods, biochemical assays, fluorescence spectroscopy and mass spectrometry; mammalian cell culture.
Cooperation partners:
Personal qualifications:
The candidate should have a strong background in biochemistry/biophysics and should be highly motivated to succeed in science. Experience in mammalian cell culture would be an advantage.