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We are welcoming applications for a 3-year studentship funded by the Institute of Ophthalmology. Closes 6 June.
UCL Department / Division: UCL Institute of Ophthalmology
Duration of Studentship: 3 years, available to start from September 2023
PhD Title: Understanding disease mechanisms and developing novel therapies for a common cause of autosomal dominant retinitis pigmentosa
Supervisor(s): Professor Jacqueline van der Spuy and Professor Mike Cheetham
We are offering a full-time, 3 year PhD studentship to investigate the disease-causing mechanisms underlying autosomal dominant retinitis pigmentosa (adRP) caused by variations in the RP1 gene, and to develop effective therapeutic interventions for RP1-associated adRP.
Retinitis pigmentosa (RP) is one of the most common inherited retinal diseases affecting an estimated 1 in 4,000 people in the UK, and autosomal dominant RP (adRP) accounts for approximately 15-25% of all cases of RP. Variations in the retinitis pigmentosa 1 (RP1) gene are a common cause of adRP, accounting for 8-10% of all UK cases. RP is characterised by night blindness and tunnel vision, followed by the loss of central vision, and individuals with RP1-associated adRP typically begin to experience problems with vision in the second or third decade of life. RP1 variations that cause adRP all reside within a mutational ‘hotspot’ in the gene, however the underlying disease mechanism is not fully understood and the clinical phenotype of RP1-associated adRP is highly variable. Moreover, there is currently no cure or treatment for adRP caused by RP1 variations. Therefore, there is an unmet need not only to understand how RP1 ‘hotspot’ variations cause disease but also to develop targeted therapies to treat the disease.
The project will first focus on in vitro characterisation of adRP associated RP1 variants to understand disease mechanisms using an assortment of molecular, cellular and biochemical techniques. Moreover, the project will using CRISPR gene editing to introduce the most common adRP-associated RP1 variations in the UK population into induced pluripotent stem cells (iPSC) which will be differentiated into three dimensional retinal organoids for disease modelling. We will explore the impact of the RP1 variations on the retinal photoreceptor cells within the retinal organoid model. Finally, the project will develop a number of tools for the in vitro optimisation and validation of therapeutic strategies targeting adRP-associated RP1 variations. The therapeutic approach will encompass strategies targeting the rescue, downregulation or replacement of the disease-associated allele. Successful strategies will be tested in the 3D retinal organoid model of disease.
Applicants should hold, or expect to receive, a minimum upper-second degree or equivalent in an associated subject in the biomedical or life sciences. A Master’s degree or previous lab-based research experience is desirable.
Duties and Responsibilities
The successful candidate is expected to:
- Develop a deep understanding and knowledge of the current literature relevant to the project and ensure continuous critical review of the literature throughout the project
- Develop, apply and advance the required expertise, technical and analytical skills to successfully achieve the desired research goals
- Keep precise, well-organised and detailed records of all research
- Work in collaboration with other researchers
- 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 and department, and be aware of UCL policies
Person Specification
- A good degree (2.1 or above; or equivalent EU/overseas degree) and/or MSc in an appropriate field (biomedical or life sciences)
- Demonstrable interest in the translational medicine field
- Experience with statistical methods and software packages
- Experience of image processing
- Excellent methodological, technical and analytical skills
- Excellent project planning, time management and organisational skills
- High proficiency in written and spoken English
- Very strong work ethic, with the ability to think creatively and work both individually and within a team
- Ability to work towards set deadlines
- A commitment to the highest standards of research integrity
Informal enquiries should be made to Professor Jacqueline van der Spuy (j.spuy@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 at ioo.pgr@ucl.ac.uk
Shortlisted candidates will be contacted directly for interview.
The successful candidate is expected to start on 25 September 2023, but some flexibility with respect to the start date is possible.
Funding Notes
This studentship is funded for 3 years and includes UK UCL PhD tuition fees, laboratory costs and an annual salary stipend starting at £22,000, rising to £24,000 by the final year.
Eligibility
The full studentship (tuition fees and salary stipend) is eligible to all UK nationals and some EU nationals depending on their settlement status. Only UK Home rate tuition fees can be covered.
Applicants who will incur international fees are welcome to apply but they must show that they can supplement the difference between UK and international fees (currently £26, 240 per year) in their application.
Application deadline: Tuesday 6 June 2023
Proposed interview date: To be confirmed