Project Reference: TRG27-IMR-JN1

Project title: Intracellular trafficking mechanisms in synaptic plasticity

Project outline

Synaptic plasticity is the ability of connections between neurons to strengthen or weaken with activity, and is fundamental to learning, memory and healthy brain development. Many forms of plasticity depend on moving proteins to and from the neuronal cell surface. While the trafficking of AMPA-type glutamate receptors has been studied in detail, we know far less about the wider set of proteins that are repositioned during plasticity, how their movement is controlled, or why these changes are important.

This PhD will investigate how neurons reorganise their surface proteome during two major forms of synaptic plasticity: long-term potentiation, which strengthens active synapses, and homeostatic synaptic scaling, which helps stabilise neuronal activity. The project will identify proteins that change location during each process, determine the cellular trafficking pathways that move them, and test which of these changes are required for plasticity.

The student will combine human iPSC-derived neurons with quantitative proteomics, high-resolution fluorescence microscopy and molecular cell biology. Unbiased proteomic approaches will be used to discover activity-dependent changes in protein localisation, while live-cell and fixed-cell imaging will define when and where candidate proteins move. Genetic and molecular perturbations will then test the trafficking machinery involved and determine whether individual relocalisation events are necessary for changes in synaptic strength.

By comparing potentiation and homeostatic scaling, the project will reveal both shared and distinct mechanisms through which neurons remodel their cell surface, helping us understand how synapses remain adaptable while neuronal circuits remain stable.

Principal Supervisor

Dr Jonathon Nixon-Abell

Email address: jjn36@cam.ac.uk

Department / Partner Institute: Cambridge Institute for Medical Research (CIMR)

Website: https://www.cimr.cam.ac.uk/staff/dr-jonathon-nixon-abell

BBSRC strategic theme

Understanding the rules of life