Project Reference: ICS27-SAN-ML1

Project title: Developing extracellular vesicle assays as molecular readouts of brain biology and drug action

Project outline

Every cell in the body constantly sheds tiny membrane‑wrapped packages called extracellular vesicles (EVs). Each vesicle carries proteins and genetic material from the cell that released it, and travels out into the blood. Using distinctive surface markers on these vesicles, we can enrich for vesicles from a specific cell type, for example astrocytes or neurons, giving a readout of molecular signals from different brain cell types in a blood sample. EVs thus offer a minimally invasive window into the living human brain, which is otherwise impractical to sample. This is especially valuable for drugs that reshape brain biology over time: some, such as compounds in Compass Pathways' pipeline, appear to drive durable molecular changes from a single dose.

This PhD will develop existing extracellular vesicle assays into robust molecular readouts of brain cell biology and of how drugs act on the brain. Working with our industrial partner Compass Pathways, whose treatments and pipeline assets engage different neurotransmitter systems, the student will: (1) refine and benchmark methods to capture brain‑derived vesicles from biofluids and measure their protein and RNA cargo using high-throughput technologies; (2) test, in cell‑based and preclinical models, whether the EV cargo captures how drugs affect their known targets and downstream signalling; (3) use comparative drug studies in rodents to map how EV profiles change as a function of pharmacology over time; and (4) use human samples to compare vesicle‑based proteomic profiles with standard plasma proteomics, testing whether EVs carry more brain‑specific information on clinical status or target engagement.

By the end of the PhD the student will have developed and validated EV assays that report on drug action and cellular function in the brain, and developed skills in molecular biology, high‑throughput omic profiling and functional genomics.

Principal Supervisor

Dr Mary-Ellen Lynall

Email address: mel41@cam.ac.uk

Department / Partner Institute: Sanger Institute

Website: https://www.biomindlab.co.uk

Industrial Partner

Compass Pathways

BBSRC strategic theme

Bioscience for an integrated understanding of health