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Developing optogenetic therapies for retinal degeneration


Project Description

Retinal degeneration is the leading cause of blindness in developed countries. The new exciting biological approach of optogenetic therapy in which ectopic expression of photosensitive proteins (photopigments) is used to restore photosensitivity, offers a potential breakthrough for treating these conditions. Optogenetic therapy has shown very promising results in animals. However, in order to maximise clinical potential a number of important questions must be addressed: 1) Which photopigments provides the best vision? Addressing this deficit will identify the most promising photopigment(s) for clinical development and 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 an exciting time for the wider field of ocular gene therapy with numerous clinical trials ongoing 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. The student will receive expert training in highly sought-after techniques (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 and have excellent preparation for future work in biomedical research and regenerative medicine.

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.

Techniques/training to be provided:
The student will gain a strong grounding in numerous key biomedical techniques including: viral 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.

Entry Requirements:
Candidates are expected to hold (or be about to obtain) a minimum upper second class honours degree (or equivalent) in a related area / subject. Candidates with experience in in vivo experiments or with an interest in electrophysiology are encouraged to apply.

For international students we also offer a unique 4 year PhD programme that gives you the opportunity to undertake an accredited Teaching Certificate whilst carrying out an independent research project across a range of biological, medical and health sciences. For more information please visit http://www.internationalphd.manchester.ac.uk

Funding Notes

Applications are invited from self-funded students. This project has a Band 2 fee. Details of our different fee bands can be found on our website (View Website). For information on how to apply for this project, please visit the Faculty of Biology, Medicine and Health Doctoral Academy website (View Website).

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

Ballister ER, Rodgers J, Martial F, Lucas RJ (2018) A live cell assay of GPCR coupling allows identification of optogenetic tools for controlling Go and Gi signaling. BMC Biology 16(1):10

Milosavljevic N, Storchi R, Eleftheriou CG, Colins A, Petersen RS, Lucas RJ. Photoreceptive retinal ganglion cells control the information rate of the optic nerve. Proc Natl Acad Sci U S A. 2018 Dec 11;115(50):E11817-E11826

Gerrard E, Mutt E, Nagata T, Koyanagi M, Flock T, Lesca E, Schertler GFX, Terakita A, Deupi X, Lucas RJ. (2018) Convergent evolution of tertiary structure in rhodopsin visual proteins from vertebrates and box jellyfish. Proc Natl Acad Sci U S A 115(24):6201-6206

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