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Cryo-EM studies of amyloid fibrils and their mechanisms of formation in vitro and in vivo


Project Description

Amyloidosis is a pathological condition associated with the aggregation of proteins into fibrils, and is the underlying pathology in diseases such as Alzheimer’s and Parkinsons diseases. Despite the importance of this process to diseases that shape today’s society, therapies remain remote.

In this project we will use state of the art imaging technologies to gain fundamental biological insight. Specifically, we will use the Titan Krios cryo-EM microscopes in Leeds to determine the structure of amyloid fibrils formed from the protein 2-microglobulin and natural variants which cause enhanced amyloid disease. Using biochemical and biophysical assays, combined with cryo-EM, we will determine how amyloid fibrils form and how they bind essential cellular components including molecular chaperones. Finally, you will use cell biology, super resolution imaging and cryo-ET and cryo X-ray tomography to examine fibril formation within living cells.

Overall, therefore, the aim is to provide new mechanistic insights into fibril structure and fibril-induced cellular disruption by exploiting modern cryo-EM to the full.

For more information about the Radford group and for recent publications please see http://www.astbury.leeds.ac.uk.

Funding Notes

White Rose BBSRC Doctoral Training Partnership in Mechanistic Biology
4 year fully-funded programme of integrated research and skills training, starting Oct 2019:
• Research Council Stipend
• UK/EU Tuition Fees
• Conference allowance
• Research Costs

Requirements:
At least a 2:1 honours degree or equivalent. We welcome students with backgrounds in biological, chemical or physical sciences, or mathematical backgrounds with an interest in biological questions.
EU candidates require 3 years of UK residency in order to receive full studentship

Not all projects advertised will be funded; the DTP will appoint a limited number of candidates via a competitive process.

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References

For more information about the Radford group and for recent publications please see http://www.astbury.leeds.ac.uk.

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

FTE Category A staff submitted: 60.90

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

Click here to see the results for all UK universities

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