Probing the mechanism of Programmed Axon death using Protein Design
Not stated
- Funding
- Competition Funded PhD Project (Students Worldwide)
- Application deadline
- 8 December 2026
About the project
About the Project 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