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(MRC DTP) Developing optogenetic therapies for retinal degeneration

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  • Full or part time
    Prof R Lucas
    Dr Nina Milosavljevic
  • Application Deadline
    No more applications being accepted
  • Competition Funded PhD Project (European/UK Students Only)
    Competition Funded PhD Project (European/UK Students Only)

Project Description

Retinal degeneration is the leading cause of blindness in developed countries. In conditions such as age-related macular degeneration and retinitis pigmentosa, progressive death of photoreceptors leads to severe and irreversible loss of visual function. The new exciting biological approach of optogenetic therapy offers a potential breakthrough for treating these conditions. In this approach, viral delivery of photosensitive proteins (photopigments) to remaining cells in degenerated retinas restores photosensitivity. Optogenetic therapy has shown very promising results in animals, with impressive levels of vision restored to mice with inherited retinal degeneration. However, in order to maximise clinical potential of the optogenetic approach for curing blindness a number of important questions must be addressed: 1) The mouse studies have shown that various photopigments can function in the degenerate retina, but direct comparisons upon which to answer the question of which photopigment provides the best vision are absent. Addressing this deficit will not only identify the most promising photopigment(s) for clinical development but also determine which aspects of their function should be targeted for future improvement. 2) Vision is the property of the brain and up to now the impact of network remodelling that occurs during retinal degeneration on the therapeutic effectiveness has not been addressed. Understanding this aspect is of paramount importance for defining the therapeutic window (at what stage in retinal degeneration to intervene).

This is a great time for ocular gene therapy in general with a few gene therapies already in clinical trials and one clinically approved that may be offered by NHS as of January 2020. This project offers a fantastic opportunity to answer important questions and move the optogenetic gene therapies closer to successful clinical application. Working with the supervisory team, the successful applicant will receive expert training in a range of highly sought after techniques that represent an excellent preparation for future work in biomedical research and regenerative medicine. The student will graduate with a good practical experience of gene delivery, in vivo and surgical techniques (including the use of large scale in vivo and in vitro electrophysiological recording), molecular biology techniques (including optogenetics and viral vector design), and live-cell reporter assays and tissue culture.

The successful applicant join a dynamic and multidisciplinary group spanning molecular biology, systems physiology and computational approaches. The supervisory team have an outstanding track record in research excellence and have an active and successful program developing innovative optogenetic therapies for retinal degeneration.

Entry Requirements:
Applications are invited from UK/EU nationals only. Applicants must have obtained, or be about to obtain, at least an upper second class honours degree (or equivalent) in a relevant subject.

Funding Notes

This project is to be funded under the MRC Doctoral Training Partnership. If you are interested in this project, please make direct contact with the Principal Supervisor to arrange to discuss the project further as soon as possible. You MUST also submit an online application form - full details on how to apply can be found on the MRC DTP website www.manchester.ac.uk/mrcdtpstudentships

As an equal opportunities institution we welcome applicants from all sections of the community regardless of gender, ethnicity, disability, sexual orientation and transgender status. All appointments are made on merit.

References

Cehajic-Kapetanovic J, Eleftheriou CG, Allen AE, Milosavljevic N, Pienaar A, Bedford R, Davis KE, Bishop PN, Lucas RJ. (2015) Restoration of vision with ectopic expression of human rod opsin. Current Biology 25(16):2111-22

Storchi R, Bedford RA, Martial FP, Allen AE., Wynne J, Montemurro MA, Petersen RS, Lucas RJ. (2017) Modulation of fast narrowband oscillations in the mouse retina and dLGN according to background light intensity. Neuron 93(2):299-307



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