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  MSc By Research: Patient-derived induced pluripotent stem cells as a test bed for new therapies for aniridia-associated keratopathy


   School of Medicine, Medical Sciences & Nutrition

  , Dr Kaja Kostanjevec  Applications accepted all year round  Self-Funded PhD Students Only

About the Project

The MSc by Research programme at the University of Aberdeen is for students interested in a research-intensive master's degree. It is designed specifically to enhance your skills for a PhD or research career. If you have your own ideas for a research project in this area, we would love to hear from you! Please reach out to one of the project supervisors above to discuss your ideas.

You can find further information about our academic requirements and programme structure here.

Aniridia-associated keratopathy (AAK) is a potentially blinding genetic eye disease caused by heterozygous mutation in the eye ‘master regulator gene’, PAX6. Patients have no irises (= ‘aniridia’) but more seriously suffer a progressive loss of vision in postnatal life due to opacification of the cornea, our so-called ‘window on the world’. This opacification is what is known as AAK. Our lab has spent over 20 years studying how mutation in PAX6 leads to AAK in humans, mostly using mouse models of Pax6 mutation. We have shown that substantially the problem is one of oxidative stress – our ‘triple whammy’ model has shown that the Pax6 mutant cornea is 1) fragile and loses barrier function leading to 2) high levels of oxidative stress compounded by 3) reduced expression of stress-protective proteins in the cornea.

There is currently no cure for AAK and we are researching eyedrop therapies that can either work directly on the gene defect i.e. by increasing Pax6 dosage in the cornea, or that can work on the symptoms i.e. by reducing oxidative stress. One putatively therapeutic compound is the bio-active reducing agent, glutathione, which has previously been marketed as a treatment for cataracts, but which has never been tried for AAK.

The masters project will form part of our proof of principle that glutathione can form part of a treatment regime potentially beneficial for AAK. In partnership with postdoctoral researcher Kaja Kostanjevec, the student will assay the ability of glutathione, alone or in combination with other drugs, to improve PAX6 dosage in human patient-derived induced pluripotent stem cells (iPSCs). Oxidative stress and gene expression will be compared in treated and control cells. Training will be provided in phenotype assessment alongside histology, western blot, immunohistochemical and the maintenance and differentiation of iPSCs

At the end of the project, the intention is that the student will be able to advise a go/no go decision on whether we should progress glutathione to clinical trial. You will be part of ‘Team Finn’ – a collaboration of researchers and funders set up around a young boy, Finn, who has AAK.

Applicants to this project should hold a minimum of a 2:1 UK Honours degree (or international equivalent) in a relevant subject.

We encourage applications from all backgrounds and communities, and are committed to having a diverse, inclusive team.

Informal enquiries are encouraged, please contact Martin Collinson () for further information.

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APPLICATION PROCEDURE:

Please note: This is a self-funded opportunity.

  • Prospective students should contact the lead supervisor (via the email address listed above) to discuss the research project and complete a proposal form prior to / or shortly after applying.
  • Formal applications can be completed online: https://www.abdn.ac.uk/pgap/login.php
  • You should apply for Medical Sciences (MSc) to ensure your application is passed to the correct team.
  • Please clearly note the name of the supervisor and the project title on the application form. If this is not included, your application may not be considered for the project.
  • Candidates should have (or expect to achieve) a minimum of a 2:1 UK Honours degree (or international equivalent) at undergraduate level.
  • Your application must include: a personal statement, an up-to-date copy of your academic CV, and clear copies of your educational certificates and transcripts.
  • If you are still undertaking your undergraduate degree, it is helpful to the selection panel if you could provide documentation showing your grades to date (this can be a screenshot from an online portal).
  • Please note: Project supervisors will not respond to requests for funding assistance.
  • If you require any additional assistance in submitting your application or have any queries about the application process, please don't hesitate to contact us at 
Biological Sciences (4) Medicine (26)

Funding Notes

This is a self-funding project open to students worldwide. Our typical start dates for this programme are February or October.
Fees for this programme are £4,712 for home/UK students, and £24,860 for international students.
Additional research costs / Bench fees of £3,000 will also apply.
The Scottish Government offers postgraduate loans to those due to start a Masters (taught or research) programme.

References

1) Latta L, Figueiredo FC, Ashery-Padan R, Collinson JM, Daniels J, Ferrari S, Szentmáry N, Solá S, Shalom-Feuerstein R, Lako M, Xapelli S, Aberdam D, Lagali N. (2021). Pathophysiology of aniridia-associated keratopathy: Developmental aspects and unanswered questions. Ocul Surf. 22: 245-266.
2) Ou, J., Lowes, C. & Collinson JM. 2010. Cytoskeletal and cell adhesion defects in wounded and Pax6+/- corneal epithelia. Invest. Ophthalmol. Vis. Sci. 51: 1415-1423.
3) Ou, J., Walczysko, P., Kucerova, R., Rajnicek, A. M., McCaig, C. D., Zhao, M. & Collinson, J. M. 2008. Chronic wound state exacerbated by oxidative stress in Pax6+/- aniridia-related keratopathy. J. Pathol. 215: 421–430.

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