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Super-resolution microscopy to investigate the link between innate immunity and Parkinson's disease


School of Chemistry

Dr Matthew Horrocks Thursday, February 04, 2021 Funded PhD Project (Students Worldwide)
Edinburgh United Kingdom Analytical Chemistry Biophysics Biotechnology Immunology Medical Physics Neuroscience Optical Physics Virology

About the Project

This project is one of 19 four year PhD Studentships funded by Medical Research Scotland (https://www.medicalresearchscotland.org.uk) to be delivered jointly by the named University and External Partner Organisation (EPO). The Studentship will provide the first-class academic and additional training provided by the EPO needed to equip the successful candidate for a science career in an increasingly ompetitive market.

"Investigating the link between neural innate immunity and Parkinson's disease" to be delivered by the University of Edinburgh [Supervisors: Dr Matthew Horrocks (School of Chemistry, University of Edinburgh), Dr Tilo Kunath (Centre for Regenerative Medicine, University of Edinburgh), Dr Michele Zagnoni (Electronic and Electrical Engineering, University of Strathclyde) and Dr David Beckham (Departments of Medicine and Immunology and Microbiology, University of Colorado)] and Oxford Nanoimaging (ONI) Limited (http://www.oni.bio) [External Partner Organisation supervisor: Dr James Felce].

We possess a number of ways to fight viruses and bacteria. An evolutionary ancient mechanism to protect us from pathogens is the innate immune system. The Parkinson’s-associated protein, alpha-synuclein (α-syn), has recently been discovered to play a significant role in innate immunity. Specifically, α-syn helps to protect nerves from virus infection, but in doing so, can adopt a conformation that leads to Parkinson's disease (PD) in future life.

Fluorescence microscopy allows the conformations of proteins to be observed in biological samples. Until recently, however, the wavelike nature of light and its associated diffraction, limited the resolution of optical microscopy to ~200 nm. New ‘super-resolution’ fluorescence microscopy methods, have been developed to overcome the diffraction limit of ‘traditional’ microscopy. The enormous impact of super resolution microscopy methods was recognized by its inventors being awarded the Nobel Prize in Chemistry (2014). Super resolution methods can increase the resolution of fluorescence microscopy down to ~5 nm, thus enabling the observation of molecular processes in great detail.

In this project, the student will use super-resolution microscopy and advanced microfluiodics to characterise the forms of α-syn generated after infection in IPSC-derived neurons, and investigate their similarity to those formed in PD.

Training: the supervisors of this project will combine their expertise in brain immunity (Beckham), neuroscience (Horrocks/Kunath/Beckham), super-resolution microscopy techniques (Horrocks/Felce), and microfluidics (Zagnoni). The training will be achieved primarily through practical application of the research techniques within the supervisors’ laboratories, in addition to spending time with our industrial partner, ONI. Skills that will be developed include cell and molecular biology techniques, cell culture (including differentiated induced pluripotent stem cells), advanced microscopy (single-molecule and super-resolution), data analysis and coding. The student will be encouraged to participate in training workshops, to present in various multi-group meetings at the University, and to participate in public engagement activities.

ENQUIRIES:

Enquiries should be sent to Dr Matthew Horrocks:

School of Chemistry, University of Edinburgh, David Brewster Road, Edinburgh EH9 3FJ, UK. Email:

APPLICATIONS:

Applicants must have obtained, or expect to obtain, a first or 2.1 UK honours degree, or equivalent for degrees obtained outside the UK, in an appropriate science/technology area.

Applicants should send a CV, the contact details of 2 or 3 referees (including email addresses) and a covering letter, describing your previous research experience and explaining your reasons for applying for this particular project, by email to Dr Matthew Horrocks:

Please note, your application may be shared with the funders of this PhD Studentship, Medical Research Scotland and ONI Ltd .

Interviews are expected to take place 3-4 weeks after the closing date for applications. In light of the current coronavirus situation, interviews may be conducted by video conference.

It is anticipated that the PhD Studentship will start 1 October 2021.


Funding Notes

PhD Studentship provides: an annual tax-free stipend of £18,500, increasing to £19,000 over the four years; tuition fees at UK/EU rates only; consumables; and generous travel allowance.
International fees are not covered. International students applying for the Studentship must provide evidence by the date of interview that they are able to finance the fee top-up required to the international fee level.

References

http://www.smbiophysics.org

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