PhD Studentship: Using novel human isogenic SARM1 knockin and knockout cells to investigate axon degeneration in MND

This studentship investigates the axon degeneration protein SARM1, an exciting target for therapy in a wide range of neurological conditions. Knocking out SARM1 protects neurons in a TDP-43 transgenic mouse model of amyotrophic lateral sclerosis (ALS). A direct link between SARM1 and ALS is strongly suggested by genomic studies that identified variants in SARM1 associated with increased ALS risk and SARM1 gain of function mutations in ALS patients. Interestingly, these mutations are lethal in vitro when overexpressed. How patients carrying these alleles can survive into adulthood is unclear, but endogenous protective factors must be responsible, and these could have therapeutic value. Surprisingly, how SARM1 behaves in neurons in real time and what proteins it interacts with remain unknown.

To address these questions, the student will use isogenic SARM1 knock-in human induced pluripotent stem cells (iPSCs) with GoF mutations (E340K, del275-276 and A275V), SARM1 knockout and a homozygous intronic SNP linked with increased ALS risk.

The successful candidate will work within the vibrant Department of Basic and Clinical Neuroscience under the supervision of clinician scientist Dr Jemeen Sreedharan and Prof Kei Cho MBE. The student will be well supported by experienced postdoctoral researchers in a highly collaborative laboratory and will also have the opportunity to meet and interact with patients in Dr Sreedharan’s clinic. In the lab, the student will learn a broad pallet of techniques to enable them to perform cutting-edge research to develop urgently needed treatments for ALS. The student will:

1. Study how ALS-linked SARM1 variants influence axonal structure, transport and neurodegeneration using transcriptomics, metabolomics, immunocytochemistry and electrophysiology.
2. Tag endogenous SARM1 using CRISPR. This will allow for live imaging and pull-downs to enable interactome studies under normal and stressed conditions.
3. Manipulate pathways implicated from the above studies for therapeutic evaluation in SARM1 and other ALS mutant cell lines available through the UK MND Research Institute.

Applicants must complete and submit an online admissions application, via the admissions portal by midnight (23:59 GMT), 26th March 2026.

On the ‘Choosing a programme’ page, please select Basic and Clinical Neuroscience Research PhD Full-time

More information on the department and the programme is available here: https://www.kcl.ac.uk/neuroscience/about/departments/basic-clinical-neuroscience

In your application, you need to include:

• Academic Transcripts - submitted with the online admissions application
• Details of your qualifications - you will need to attach copies
• Details of previous employment - please include your CV
• A personal statement describing your interests and why you wish to apply for this project. Please include this as an attachment rather than using the text box.
• Academic References – all admissions applications require one supporting reference. If the applicant is relying on their referees to submit a reference directly to the College after they have submitted their admissions application, then the applicant must ensure that their chosen referee is made aware of the deadline and that the reference needs to be sent from an institutional email address.

In the Funding section, please tick box 5 and include the following reference: JS-IOPPN-MNDA-26

Please note there is no need to complete the Research Proposal section in your application.

You are welcome to email Dr Jemeen Sreedharan (Jemeen.Sreedharan@kcl.ac.uk) for more information regarding the project and studentship.

If you have any queries regarding the application process, please contact the Education support team at ioppn.pgr@kcl.ac.uk.

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