Ruprecht-Karls-Universit├Ąt Heidelberg
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Bukau0318 - Scientist (f/m) / PhD position
Project no:
Bukau0318

Project leader:

Project supervisor:
Bukau, Bernd
Application deadline:
30. Nov 2018
Start of PhD project:
1. Jan 2019

Project description:

Title:
Working principles of the Hsp70 chaperone system in cancer biology: J-protein substrate selection determines Hsp70 action on p53
Summary:
As guardian of the proteome, tumour suppressor protein p53 accumulates mutations that destabilise its interaction with DNA in most types of cancer, enabling the tumour cell to escape programmed cell death. In apparent contradiction, the human chaperone Hsp70 plays a key role in regulating both the folding/stabilisation and degradation of mutated p53. Such triage decision can have fundamental consequences on the determination of cancer cell faith, making Hsp70 an attractive target for therapeutic intervention. We aim to understand the mechanistic basis of the Hsp70-p53 interaction and how the various cellular outcomes are regulated by the concerted action of Hsp70 co-chaperones.
References:
Rosenzweig R, Sekhar A, Nagesh J, Kay LE. (2017) Promiscuous binding by Hsp70 results in conformational heterogeneity and fuzzy chaperone-substrate ensembles. Elife 6.

Nillegoda, N.B., Kirstein, J., Szlachcic, A., Berynskyy, M., Stank, A., Stengel, F., Arnsburg, K., Gao, X., Scior, A., Aebersold, R., Guilbride, D.L., Wade, R.C., Morimoto, R.I., Mayer, M.P. and Bukau, B. (2015). Crucial HSP70 co-chaperone complex unlocks metazoan protein disaggregation. Nature 524, 247-251.
Methods that will be used:
Chaperone biochemistry, fluorescence spectroscopy, molecular biology, CRISPR/Cas9 and cell culture based methods.
Cooperation partners:
Rosenzweig laboratory at the Weizmann Institute in Rehovot, Israel.
Personal qualifications:
We are looking for highly motivated PhD students with a keen interest in protein misfolding diseases and cancer biology. Previous experience with molecular chaperones or biophysical techniques are of advantage but not required. Due to the collaborative nature of the project successful candidates will have excellent communication skills, work efficiently both independently and as part of a team of international researchers, with a good mastery of English.
Keywords:
Molecular chaperones, Hsp70 system, p53, cancer