Ruprecht-Karls-Universität Heidelberg
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Bukau0218 - Scientist (f/m) / PhD position
Project no:
Bukau0218

Project leader:

Project supervisor:
Bukau, Bernd
Application deadline:
31. Oct 2018
Start of PhD project:
1. Dec 2018

Project description:

Title:
Modulation of protein aggregation by molecular chaperones in neurodegeneration
Summary:
The gradual accumulation of proteins into ordered, amyloid-type aggregates is a shared characteristic of debilitating neurodegenerative conditions such as Alzheimer’s and Parkinson’s disease. As regulators of protein folding states, molecular chaperones are uniquely placed to interfere in the formation and aid the clearance of such aggregate deposits in the early stages of disease. To unravel the potentially pivotal role of molecular chaperones in neurodegeneration, we aim to build a mechanistic understanding of the role of the Hsp70 chaperone machinery in the formation, clearance and propagation of amyloid fibrils and the key role of co-chaperones in modulating such diverse Hsp70 activities.

As part of an international research consortium, this project will identify (co-) chaperones with promising therapeutic potential using biochemical and cell biology approaches in collaboration with the Nussbaum-Krammer group.
References:
Nillegoda, N.B., Wentink, A.S., Bukau, B. (2018) Protein Disaggregation in Multicellular Organisms. TiBS 43, 285-300.

Gao, X., Carroni, M., Nussbaum-Krammer, C., Mogk, A., Nillegoda, N.B., Szlachcic, A., Guilbride, D.L., Saibil, H.R., Mayer, M.P., and Bukau, B. (2015). Human Hsp70 Disaggregase Reverses Parkinson's-Linked alpha-Synuclein Amyloid Fibrils. Mol Cell 59, 781-793.

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 and amyloid biochemistry, electron microscopy, fluorescence spectroscopy, molecular biology, CRISPR/Cas9 and cell culture based methods.
Cooperation partners:
National and international consortium partners. Nussbaum-Krammer group at the ZMBH.
Personal qualifications:
We are looking for highly motivated PhD students with a keen interest in protein misfolding diseases. Previous experience with molecular chaperones or biophysical techniques are of advantage but not required. Due to the collaborative nature of the project succesful 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, amyloid fibrils, neurodegeneration