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Investigating the impact of chaperone activation on tauopathy in Alzheimer’s Disease

  • Full or part time
  • Application Deadline
    Sunday, January 05, 2020
  • Competition Funded PhD Project (European/UK Students Only)
    Competition Funded PhD Project (European/UK Students Only)

Project Description

Dementia is an age-linked progressive disorder that affects around 850,000 people in the UK. Causing a substantial economic and social impact, it presents one of the toughest medical challenges with no effective therapy available for the disease. Alzheimer’s Disease (AD) is the most common form of dementia followed by Frontotemporal Dementia (FTD), both are characterised by significant neuronal loss in respective brain area that leads to mental decline. Accumulation of aberrant protein such as tau is observed in both conditions which linked closely to cognitive symptoms and neuronal damage.
To deal with misfolded proteins, cells use a group of chaperones called Heat Shock Proteins (HSPs) as gate keepers in maintaining protein homeostasis. Levels of HSPs are maintained in a basal level in resting states, but are induced during the heat shock response (HSR) via the activation of Heat Shock Factor 1 (HSF1) in response to cellular stress. Studies have shown that threshold of HSR activation is particularly high in neurons and that the levels of neuronal HSPs decline in several neurodegenerative disorder including AD, implying the involvement of chaperone activity in the build-up of the pathological tau aggregates. To further examine the detailed impact of HSR activation on tauopathy, features of tau protein pathology seen in AD patients, this project will manipulate HSF1 to control the overall expression of all HSPs, and characterise the involvement of HSR/HSPs in the development of tauopathy. The specific aims of this project are:
1. Characterise the impact of HSR activation on various toxic tau species
2. Identify the chaperone/co-chaperone involved in tau folding or degradation
Status of tau will be examined through biochemical, biophysical and cellular imaging. Cellular response will be first characterized in cellular model and validated in primary neurons. The aggregation of tau protein will also be examined in vitro.

Funding Notes

The studentship is fully funded for three years by the Department of Biology and covers: (i) a tax-free annual stipend at the standard Research Council rate (£15,000 estimated for 2020 entry), (ii) research costs, and (iii) tuition fees at the UK/EU rate. The successful candidate will be required to contribute to departmental teaching by undertaking 30 hours/year demonstrating for Biology practicals.

References

Entry requirements: Students with, or expecting to gain, at least an upper second class honours degree, or equivalent, in a are invited to apply. We welcome applications from students with backgrounds in any relevant biosciences subject that provides the necessary skills, knowledge and experience the research project.

Start date: October 2020

How good is research at University of York in Biological Sciences?

FTE Category A staff submitted: 44.37

Research output data provided by the Research Excellence Framework (REF)

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