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Website University of Cambridge
Closing date: 8th December
A competition-funded PhD at the University of Cambridge with Prof Michael Coleman, designing new forms of the enzyme SARM1 to study programmed axon death, a pathway involved in many neurodegenerative diseases. Open to UK and international applicants. See more funded PhDs.
Summary
Programmed axon death is an intrinsic death programme in axons, executed by the NAD degrading enzyme SARM1 and regulated by the NAD synthesising enzyme NMNAT2. The programme can be activated by axon injury, gene mutation, metabolic perturbations, toxins and viruses and is involved in many neurodegenerative diseases.
Human genetics points to roles in polyneuropathies and motor neuron disease, while animal studies strongly suggest wider relevance also in peripheral neuropathies, glaucoma, viral encephalitis, traumatic brain injury, Parkinson’s disease and possibly multiple sclerosis. With the recent success of a Phase I clinical trial for SARM1 inhibitors and others in development, it is an important time to develop new tools to study the pathway further.
Project Aims
SARM1 is a modular protein composed of ARM, SAM and TIR domains. CryoEM and crystal structures of each domain and the holoprotein are available, both in its inactive and activated forms. Against this background the aim of this project is to perform rational design of variant forms of SARM1, or hybrids with reporter molecules, to act as tools for studying SARM1 activation, stability, enzyme activity and post-translational modification.
The successful candidate will gain skills in molecular cloning, site directed mutagenesis, enzyme assays, primary and hiPSC-derived neuron cell cultures, transfection and structural analysis and will contribute to both basic biological knowledge and drug discovery efforts in this area.
Our research group has a strong collaborative and supportive culture with many opportunities for conference participation and personal and professional development.
How to Apply
If you are interested in this project, please go to the University pages and apply via the online portal;
PhD https://www.postgraduate.study.cam.ac.uk/courses/directory/cvcnpdpcn/apply
Research MPhil https://www.postgraduate.study.cam.ac.uk/courses/directory/cvcnmpmds/apply
Funding Notes
For academic year October 27/28;
Gates US applications (round 1) close 14th October 26, further information available via Gates Website; View Website
Cambridge Trust, Gates Cambridge (round 2) deadline 8th December 26 to be eligible for funding. If you apply after the funding deadlines you will not be eligible for the Cambridge Funding competition, please indicate in your application all the funding you are eligible for. You can also check funding search Search – Postgraduate Funding Search
Funding is not available for Lent or Easter 27 places as the funding deadline for these has already passed, you will need to have other funding in place to support your studies
Suggested Reading
- Coleman and Hoke, Nat Rev Neurosci 21: 183-196 (2020)
- Gilley et al, eLife 10: e70905
- Loreto et al, Neurobiol Dis 213: 106986
To apply for this job please visit www.postgraduate.study.cam.ac.uk.
