Ruprecht-Karls-Universität Heidelberg
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Mayer0119 - Scientist (f/m) / PhD position
Project no:
Mayer0119

Project leader:

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

Project description:

Title:
Interaction of Hsp90 with cochaperones and client proteins
Summary:
In the center of this PhD project is the molecular mechanism of the Hsp70-Hsp90 chaperone machinery. Hsp70 and Hsp90 together with a large number of cochaperones form dynamic complexes with some 200 proteins in a native or near native state. Many of these “client” proteins are receptors, protein kinases and transcription factors involved in signal transduction and cell cycle regulation and depend on their interaction with Hsp70 and Hsp90 to become responsive to upstream signals. Thus, the Hsp70-Hsp90 chaperon machine is a key regulator of cell homeostasis, proliferation, differentiation, and programmed cell death and in recent years became a prime target for anti-tumor therapy. In this PhD project the fundamental questions are investigated of how the chaperone machine can interact with so many client proteins that are not related in sequence or structure and how this interaction regulates stability and activity of the clients. These questions will be addressed with biochemical and biophysical techniques using purified proteins. Complementary in-vivo-experiments will be carried out in yeast and mammalian cell culture.
References:
Graf C, Stankiewicz M, Kramer G, Mayer MP (2009) Spatially and kinetically resolved changes in the conformational dynamics of the Hsp90 chaperone machine. EMBO J 28: 602-613

Mayer MP & Le Breton L (2015) Hsp90: Breaking the Symmetry. Mol Cell 58: 8-20

Nguyen, M. T. N. et al. Isoform-Specific Phosphorylation in Human Hsp90β Affects Interaction with Clients and the Cochaperone Cdc37. Journal of Molecular Biology 429, 732–752 (2017).
Daturpalli, S., Knieß, R. A., Lee, C.-T. & Mayer, M. P. Large Rotation of the N-terminal Domain of Hsp90 Is Important for Interaction with Some but Not All Client Proteins. Journal of Molecular Biology 429, 1406–1423 (2017).
Methods that will be used:
Protein purification methods, biochemical assays, fluorescence spectroscopy and mass spectrometry; yeast genetics and 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 yeast genetics or mammalian cell culture would be an advantage.
Keywords: