Centre for Regenerative Medicine

PhD Opportunities

Information about available funded PhD Positions

Available studentships  

Investigating human stem cell-derived cortical neurons with the G51D a-synuclein mutation as a model for dementia with Lewy bodies  

Applications accepted up to 3rd April 2020 (UK/EU)   

1st Supervisor: Dr Tilo Kunath 

2nd Supervisor: Dr Michele Zagnoni (University of Strathclyde)

About the project

Dementia with Lewy bodies (DLB) is the second most common type of dementia after Alzheimer’s. It is characterised by a-synuclein-positive inclusions in the cortex called Lewy bodies. Recently, a family with a G51D mutation in alpha-synuclein (aSyn) was reported to have severe DLB, as well as parkinsonism (1). We have derived induced pluripotent stem cells (iPSCs) from a member of this family with the G51D mutation, and also published iPSCs from a patient with triplication of the a-synuclein gene who also suffered from DLB (2).

This PhD project with differentiate the DLB patient iPSCs into cortical neurons using a highly efficient protocol to investigate primary disease mechanisms caused by (i) G51D, and (ii) over-production of aSyn. The neurons will be differentiated in custom-designed microfluidics devices in collaboration with Dr Michele Zagnoni (University of Strathclyde), an expert in lab-on-chip applications for neuroscience and stem cell-derived neurons (3,4). Questions to address include: (i) Does G51D-aSyn aggregate in human stem cell-derived neurons? (ii) Does G51D-aSyn transfer pathology from neuron-to-neuron more efficiently than WT-aSyn? (iii) Which proteins are mis-regulated in G51D-aSyn stem cell-derived neurons, and (iv) Can small molecules reduce or eliminate G51D-aSyn induced defects in human cortical neurons?

References

  1. Kiely AP, Asi YT, Kara E, Limousin P, Ling H, Lewis P, Proukakis C, Quinn N, Lees AJ, Hardy J, Revesz T, Houlden H, Holton JL. (2013) α-Synucleinopathy associated with G51D SNCA mutation: a link between Parkinson's disease and multiple system atrophy? Acta Neuropathol. 125:753-69.
  2. Devine MJ, Ryten M, Vodicka P, Thomson AJ, Burdon T, Houlden H, Cavaleri F, Nagano M, Drummond NJ, Taanman JW, Schapira AH, Gwinn K, Hardy J, Lewis PA, Kunath T. (2011) Parkinson's disease induced pluripotent stem cells with triplication of the α-synuclein locus. Nat Commun. 2:440.
  3. Sposito T, Preza E, Mahoney CJ, Setó-Salvia N, Ryan NS, Morris HR, Arber C, Devine MJ, Houlden H, Warner TT, Bushell TJ, Zagnoni M, Kunath T, Livesey FJ, Fox NC, Rossor MN, Hardy J, Wray S. (2015) Developmental regulation of tau splicing is disrupted in stem cell-derived neurons from frontotemporal dementia patients with the 10 + 16 splice-site mutation in MAPT. Hum Mol Genet. 24:5260-9.
  4. MacKerron C, Robertson G, Zagnoni M, Bushell TJ. (2017) A Microfluidic Platform for the Characterisation of CNS Active Compounds. Sci Rep. 7:15692.

Funding Notes

This is part of a competition studentship with project 2020-CCBS-05 (see View Website). The best applicant will be offered the studentship, regardless of which project they wish to do. You can apply to both projects, but this will not offer any advantage.

The studentship includes a 3 year UKRI-level stipend, UK/EU level tuition fees, and an allowance for consumables and travel. The project would suit applicants with a background in basic neuroscience, developmental biology and molecular biology.

Apply Now

For instructions on how to apply, please refer to Edinburgh Neuroscience website

All applicants must read carefully the application instructions (download application form). Applicants are responsible for arranging for references to be submitted in support of your application.

 

MSc By Research: Regenerative Medicine and Tissue Repair Programme

Our MSc by Research in Regenerative Medicine and Tissue Repair is a one-year, full-time, on-campus Masters programme structured around two laboratory-based research projects and a research proposal writing component.

The programme is based at the MRC Centre for Regenerative Medicine (CRM), a purpose-built research environment at the heart of Edinburgh BioQuarter, with a track record in training over 180 postgraduate students.

This MSc by Research is designed to prepare you for a research career in academia or industry, whether you have recently completed an undergraduate degree or are a professional who wants to pursue a career in research. You will gain valuable transferable skills that will be beneficial in a wide range of professions.

MSc By Research: Regenerative Medicine and Tissue Repair website

Tissue Repair PhD Programme

The MRC Centre for Regenerative Medicine is one of five research centres at the Edinburgh Medical School involved in the four-year PhD Programme in Tissue Repair. This multi-disciplinary training programme is training the next generation of scientific leaders in tissue repair by providing interdisciplinary training in basic and translational biomedical research. For programme details please visit the Tissue Repair website.

Tissue Repair website

Self Funded Applicants

We encourage inquiries and applications from self-funded basic and clinical scientists and from candidates who intend to apply for external funding all year round.

Instructions on how to apply as a self funded student

Studentships can include:

  • Stipend for 3 or 4 years
  • Tuition Fees
  • Research Training Costs
  • Conference Travel Allowance

Please contact relevant principal investigators informally to discuss potential projects and visit our funding opportunities page.

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PhD funding and finance

Further information about MRC Studentships

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