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We are offering a fulltime, 3 year PhD studentship to investigate the mechanisms of RP2 and ARL3 associated retinal dystrophies using stem cell derived 3-dimensional retinal organoids.
PhD Description
UCL Department / Division: UCL Institute of Ophthalmology
Duration of Studentship: 3 years, available to start from 26 September 2022
PhD Title: Defining the RP2 retinal disease pathway for the development of potential therapeutic approaches
Supervisor(s): Prof Alison Hardcastle and Prof Mike Cheetham
We are offering a fulltime, 3 year PhD studentship to investigate the mechanisms of RP2 and ARL3 associated retinal dystrophies using stem cell derived 3-dimensional retinal organoids.
RP2 acts as a GTPase activating protein for the small GTPase ARL3. Mutations in RP2 are associated with loss of function and cause X-linked retinitis pigmentosa (RP), whereas variants in ARL3 have been associated with dominant RP and recessive Joubert syndrome. Recently, we have shown that stem cell derived retinal organoid models of RP2 disease undergo photoreceptor cell death, which was prevented by gene augmentation therapy with AAV RP2.
This studentship will explore the disease mechanisms associated with genetic variants in RP2 and ARL3 using advances in gene editing, stem cell biology and transcriptomics, and develop proof of concept for potential therapeutic approaches. The student will characterise the RP2-ARL3 pathway in human retinal cells and establish mechanisms of cell death associated with these partner proteins.
Applicants should hold, or expect to receive, a minimum upper-second degree or equivalent in a relevant subject such as molecular biology, cell biology, stem cell biology, neuroscience or general life science. A Master’s degree or previous lab-based research experience is desirable.
Duties and responsibilities
The successful candidate will be expected to:
- Maintain iPSC and differentiate to retinal cells.
- Analyse retinal organoid differentiation and morphology, transcriptomics (including RNAseq data analyses), and use gene editing and AAV vectors as potential therapies in these models.
- Work in close collaboration with other members of the Hardcastle and Cheetham groups
- Prepare progress reports
- Prepare presentations
- Travel for collaboration and other meetings or conferences
- Prepare manuscripts for submission to international peer-reviewed journals
- Contribute to the overall activities of the research team, department and be aware of UCL policies
Personal specification
- A good degree (2.1 or above; or equivalent EU/overseas degree) and/or MSc in molecular biology, cell biology, stem cell biology or neuroscience related fields
- Experience with cell culture, gene editing or RNAseq analyses, desirable
- Interest in photoreceptor biology and disease, essential.
- Excellent technical skills with clear project planning
- High proficiency in written and spoken English is required
- Very strong work ethic, with the ability to think creatively and work both individually and within a team
- Informal enquiries should be made to Professor Alison Hardcastle a.hardcastle@ucl.ac.uk or Professor Mike Cheetham michael.cheetham@ucl.ac.uk
How to apply
- Applicants should submit an application to the Research Degrees Manager ioo.pgr@ucl.ac.uk. You will be required to submit a CV, a covering letter outlining motivation, interest, and suitability for this project, and contact details for two academic referees.
- Enquiries relating to the application process should be sent to the Research Degrees Manager (ioo.pgr@ucl.ac.uk).
- Shortlisted candidates will be contacted directly for interview.
Funding Notes
- This studentship is funded for 3 years by Moorfields Eye Charity and includes UK UCL PhD tuition fees (currently £5,525), laboratory costs and a living expenses stipend starting at £22,000 and increasing yearly to £24,000 in year 3.
Eligibility
- The full studentship (tuition fees and salary stipend) is eligible to all UK nationals and some European Economic Area (EEA) and Swiss nationals depending on their settlement status https://commonslibrary.parliament.uk/eligibility-for-home-fee-status-and...
- Applicants not eligible for ‘UK’ fees would need to supplement the fees to the International rate (currently £26,680 per year) for the full 3 years
- Applicants who will incur international fees are welcome to apply and must show that they can supplement the difference between UK and international fees (currently £26,680 per year) in their application.
Key References
- SCHWARZ, N., LANE, A., JOVANOVIC, K., PARFITT, D. A., AGUILA, M., THOMPSON, C. L., DA CRUZ, L., COFFEY, P. J., CHAPPLE, J. P., HARDCASTLE, A. J. & CHEETHAM, M. E. 2017. Arl3 and RP2 regulate the trafficking of ciliary tip kinesins. Hum Mol Genet, 26, 2480-2492.
- LANE A, JOVANOVIC K, SHORTALL C, OTTAVIANI D, PANES AB, SCHWARZ N, GUARASCIO R, HAYES MJ, PALFI A, CHADDERTON N, et al. 2020 Modeling and Rescue of RP2 Retinitis Pigmentosa Using iPSC-Derived Retinal Organoids. Stem Cell Reports, 15(1), 67-79.
- Application deadline: Thursday 1 September 2022