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We are welcoming applications for a 3-Year PhD Studentship funded by Moorfields Eye Charity. 'Imaging and modulating immune responses to retinal gene therapy'. Closes: 17 March 2023
UCL Department / Division: UCL Institute of Ophthalmology
Application deadline: Friday 17 March 2023
Duration of Studentship: 3 years to start 25 September 2023
PhD Title: Imaging and modulating immune responses to retinal gene therapy
Supervisor(s): Dr Colin Chu & Prof Andrew Dick
Gene therapy for otherwise untreatable eye diseases is a promising and rapidly growing field. Suboptimal efficacy and adverse responses however from retinal gene therapy using adeno-associated virus (AAV) vectors are increasingly recognised and largely believed to result from immune responses. These processes are poorly understood and appear to be affected by dose, route and the transferred gene, so work is urgently needed to model what we are observing in patients. This could help refine our approaches to avoid these adverse effects and benefit fully from what these hopeful therapies can offer.
We will apply cutting-edge imaging technologies to study retinal immune responses to AAV using the mouse. Through a highly multiplexed immunohistochemistry technique called IBEX, we will define cellular alterations in retina and draining lymph nodes at a deeper level than ever before. It will be complemented by high resolution imaging of the dynamic interactions between immune cells and AAV-infected retinal cells in living mice. We will examine the effects of dose or route of administration and test different modifying treatments including steroids and novel depleting antibody injections.
Through this PhD studentship, several widely held assumptions across the field of gene therapy can be tested and the information would be of direct translational relevance to ongoing clinical trials. The richer data obtained using a spatial biology approach will also advance our fundamental knowledge of immune responses in the eye and identify potential avenues for controlling them.
The student will gain skills in advanced imaging platforms including adaptive optics enabled imaging of the retina in mice. Training will also be given in highly multiplexed immunohistochemistry, confocal microscopy and spatial biology. Applicants should hold, or expect to receive, a minimum upper-second degree or equivalent in an associated subject such as immunology, ophthalmology, vision or life sciences. A Master’s degree or previous lab-based research experience is desirable.
Duties and Responsibilities
- The successful candidate is expected to:
- Continue to build on and help extend our early collaborative work on immune responses to ocular gene therapy (https://www.science.org/doi/10.1126/scitranslmed.abd3438)
- To contribute to research using experimental mouse models and histology to inform clinical findings.
- Work in collaboration with other researchers and develop towards research independence
- Prepare progress reports and presentations
- Travel for collaboration and other meetings or conferences
- Prepare manuscripts for submission to international peer-reviewed scientific journals
- Contribute to the overall activities of the research team, department and be aware of UCL policies
Person Specification
- An undergraduate degree (2.1 or above; or equivalent EU/overseas degree) and/or MSc Immunology, ocular gene therapy, vision science or related experience.
- Experience in histology, immunology, gene therapy or retinal research will be advantageous.
- Experience or willingness to work in experimental research involving mice and imaging.
- Experience of writing or contributing to published research.
- Excellent analytical and methodological skills.
- High proficiency in written and spoken English is required
- Strong work ethic, with the ability to think creatively, and work both individually and within a team
How to apply
Informal enquiries should be made to Dr Colin Chu at (colin.chu@ucl.ac.uk) and see www.colinchulab.com
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.
The successful candidate is expected to start by 25 September 2023, but some flexiibility may be possible.
Funding Notes
This studentship is funded for 3 years and includes UK national rate UCL PhD tuition fees, laboratory costs and an annual stipend starting at £22,000 per year, 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.
Application deadline: Friday 17 March 2023
Proposed interview date: Week beginning Monday 3 April