PhD position to study protein misfolding/ aggregation at Univ Heidelberg ZMBH
The accumulation of terminally aggregated proteins such as amyloidogenic proteins or proteins damaged by oxidative modifications such as carbonylation, is a hallmark of several neurodegenerative diseases and cellular aging, respectively.
Using S. cerevisiae as a model organism, the group of J. Tyedmers is interested in elucidating strategies of how cells deal with terminally aggregated proteins. We observed that model substrates for aggregation accumulate in recently discovered, specialized cellular locations termed „quality control compartments“, but the mechanism of sorting as well as the fate of aggregates deposited at these sites remains largely unknown.
In the Ph.D. project, you will use the amyloid forming domain of a yeast prion called [PSI+] fused to GFP to identify cellular factors that are involved in recognition, transport and molecular arrangement of amyloid aggregates at a particular protein quality control compartment. This will employ a visual screen for genes that effect the localization of the model substrate when deleted, as well as biochemical purification strategies of aggregates to identify cellular factors that interact with the protein aggregates of question.
Performing the project will involve yeast genetics, standard molecular biology techniques, fluorescence microscopy, semi-automated screening with yeast libraries and biochemical isolation strategies for aggregates.
References:
• Tyedmers J, Mogk, A & Bukau, B (2010). Cellular strategies for controlling protein aggregation. Nat Rev Mol Cell Biol 11(11):777-88.
• Tyedmers J, Treusch S, Dong J, McCaffery JM, Bevis B, Lindquist S (2010). Prion induction involves an ancient system for the sequestration of aggregated proteins and heritable changes in prion fragmentation. Proc Natl Acad Sci U S A. 2010;107(19):8633-8
• Tyedmers J, Madariaga ML, Lindquist S (2008). Prion switching in response to environmental stress. PLoS Biol. 6(11): e294.
Profile of the candidate’s qualification:
We are looking for a highly motivated Ph.D. student who is interested to perform competitive high quality scientific research in the area of protein misfolding and aggregation. She or he will have a Masters Degree (or comparable qualification) in Life sciences and a strong background in molecular biology and/or cell biology. Previous experience in working with yeast and/or protein purification would be an advantage.
Please submit your application, including CV and references to the below mentioned e-mail addresses
j.tyedmers@zmbh.uni-Phone: +49-6221-546890
