remain poorly understood.
Within the CNS, neurons orchestrate complex brain functions, but their health is inextricably linked to the surrounding glial cells, particularly the CNS resident immune cells known as microglia. Our lab's recent work has uncovered specific metabolic perturbations that sustain aberrant microglial activation compromising neuronal fitness, leading to cell loss. However, the precise metabolic drivers that disrupt these neuron-microglia interactions within the context of MS-associated cognitive decline have not yet been identified. This project will directly address this knowledge gap by elucidating the metabolic and molecular dynamics of this pathological neuroimmune crosstalk.
Project Aims:
Aim 1: Identify specific microglial phenotypes associated with the vulnerability of distinct neuronal subpopulations in brain regions critical for cognition.
Aim 2: Uncover the key metabolic determinants that drive pathological immune responses and contribute to neuronal frailty.
Aim 3: Determine whether targeted therapeutic interference of perturbed metabolic pathways in microglia and/or neurons can restore cognitive function in a preclinical model of MS.
Experimental Strategy: This project will employ a multi-modal strategy, integrating transcriptomic studies of brain regions from both MS mouse models and human tissue. Further mechanistic insights will be gained using in vitro 2D co-culture systems of primary mouse cells and, importantly, human induced pluripotent stem cell (iPSC)-derived neurons and microglia. Functional outcomes of targeting the identified metabolic drivers will be assessed in vivo through a battery of behavioural-cognitive tests and electrophysiological recordings in a mouse model of MS.
Impact: By integrating neuroimmunometabolism and cognitive neuroscience, this project will define novel mechanisms of cognitive decline in MS. Our aim is to uncover new therapeutic targets and to open promising avenues to preserve or restore cognitive function for those living with this chronic disease.
Funding Notes
For academic year October 27/28;
Gates US applications (round 1) close 14th October 26, further information available via Gates 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
References
Application portal link; 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
Please do try to get in contact directly with the supervisor should you want to discuss the project further. If you do not hear back from the supervisor, you contact you can still include their name on the application as this will be sent to them to review as well as our committee.
Open Days
17 September 2026 - Multiple dates - University of Cambridge Postgraduate College Visit Days - Cambridge (United Kingdom) - View event
