A postdoctoral position is available at the new Cambridge Dementia Research Institute based at the Addenbrooke's Campus as a part of a multidisciplinary project between the groups of Professor David Klenerman FMedSCi FRS and Professor Maria Grazia Spillantini FMedSCi FRS. The project aims to exploit novel imaging methods properties (see Angew.Chem.Int. (2017) 56, 7750 and ACS Chemical Neuroscience (2016) 7, 399) to follow aggregation and disaggregation of full length wild-type and mutant tau in live IPS derived neurons. The 5 year project aims to address the following questions:
- Under what conditions and by which processes are tau aggregates initially formed in cells? Are significant cell stress and/or an inflammatory environment required? Why do the ubiquitin-proteasome system and the autophagy system fail to prevent aggregate formation?
- How do one or a few tau aggregates entering a cell result in the formation of additional aggregates? What factors control how long this process takes and how many aggregates are formed? How much amplification is needed for self-sustained spreading? What are the effects of aggregate-induced events, such as increased reactive oxygen species or neuroinflammation, on the rate and efficiency of spreading?
- Can we develop inhibitors of key steps in tau aggregation, including elongation and fragmentation and test them in our cell models?
The position is for a molecular/cell biologist with expertise on cell culture and protein degradation mechanisms. A background in protein degradation, tau protein or protein aggregation in neurodegenerative diseases and knowledge of IPSCs culture and differentiation will be highly advantageous. The applicant will be involved in determining how protein aggregates are degraded and why their clearance fails in cells. Applicants should have a PhD (or equivalent) and interest in working in a multidisciplinary research team. This is an ideal opportunity for a cellular biologist to collaborate with biophysicists to tackle a major biomedical problem.
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Fixed-term: The funds for this post are available for 36 months in the first instance.
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Closing date: 31st January 2018
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