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MRC DiMeN Doctoral Training Partnership: The in situ 3D molecular structure of Alzheimer’s disease-associated pathology


MRC DiMeN Doctoral Training Partnership

Leeds United Kingdom Biochemistry Biophysics Cell Biology Genetics Molecular Biology Neuroscience Pathology Pharmacology Structural Biology Toxicology

About the Project

Synapses are the microprocessors of the mind that encode and store memories. In Alzheimer’s disease (AD), synapses are damaged by the constituents of abnormal beta-amyloid plaques that accumulate in the brain. Indeed, the loss of synapses correlates most closely with cognitive decline in people with AD. Currently, no treatments are available to prevent or slow the progression of AD. 

This PhD project will initiate a collaborative project within the Astbury Centre for Structural Biology, University of Leeds between the research groups of Dr René Frank, Professor Sheena Radford FRS OBE and Dr Eric Hewitt. The aim of the project is to determine the in situ 3D molecular structures associated with AD to understand disease mechanisms and molecular pathways that can lead to the rational design of a mechanism-based therapy. To this end, we have developed methods combining mouse genetics and cryo-electron microscopy (cryoEM).

The methods used will include: i) Electron tomography and computational image processing. ii) experiments with mouse models of Alzheimer’s disease iii) Biochemical and genetic labelling. Applicants from all backgrounds, including physical, chemical and biological sciences, are encouraged to apply. Some experience with programming (e.g. Python, Matlab or similar) will be highly advantageous.

This project will generate information-rich molecular structures of the mammalian brain that are expected to provide new insights into disease mechanisms. Thus, the student undertaking this research will receive an interdisciplinary training at the cutting edge of structural biology, neuroscience, and dementia research. 

Prospective PhD students are encouraged to send an informal email enquiry to Dr René Frank in the first instance with a summary of what interests you about our research and any laboratory or computational experience to date. Please also attach your CV.

Benefits of being in the DiMeN DTP:

This project is part of the Discovery Medicine North Doctoral Training Partnership (DiMeN DTP), a diverse community of PhD students across the North of England researching the major health problems facing the world today. Our partner institutions (Universities of Leeds, Liverpool, Newcastle and Sheffield) are internationally recognised as centres of research excellence and can offer you access to state-of the-art facilities to deliver high impact research.

We are very proud of our student-centred ethos and committed to supporting you throughout your PhD. As part of the DTP, we offer bespoke training in key skills sought after in early career researchers, as well as opportunities to broaden your career horizons in a range of non-academic sectors.

Being funded by the MRC means you can access additional funding for research placements, international training opportunities or internships in science policy, science communication and beyond. See how our current DiMeN students have benefited from this funding here: http://www.dimen.org.uk/overview/student-profiles/flexible-supplement-awards

Further information on the programme and how to apply can be found on our website:

https://bit.ly/3lQXR8A 


Funding Notes

Studentships are funded by the Medical Research Council (MRC) for 3.5yrs. Funding will cover UK tuition fees and stipend only. We aim to support the most outstanding applicants from outside the UK and are able to offer a limited number of bursaries that will enable full studentships to be awarded to international applicants. These full studentships will only be awarded to exceptional quality candidates, due to the competitive nature of this scheme. Please read additional guidance here: View Website
Studentships commence: 1st October 2021
Good luck!

References

Almeida-Souza L., Frank R.A.W, Garcia-Nafria J., Colussi A., Gunawardana N., Johnson C.M., Yu M., Howard G., Andrews B., Vallis Y., McMahon H.T. A flat BAR protein promotes actin polymerisation at the base of clathrin-coated pits.
Cell 74, 325 (2018) PubMed DOI: 10.1016/j.cell.2018.05.020
Frank R.A.W., Komiyama N.H., Ryan T.J., Zhu F., O’Dell T., Grant S.G.N. (2016). NMDA receptors are selectively partitioned into complexes and supercomplexes during synapse maturation.
Nature Communications 7, 11624 (2016) PubMed DOI: 10.1038/ncomms11264
Iadanza MG, Jackson MP, Hewitt EW, Ranson NA, Radford SE. A new era for understanding amyloid structures and disease.
Nature Reviews Molecular Cell Biology 19:755 (2018) PubMed DOI: 10.1038/s41580-018-0060-8

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