PhD: Protein Aggregates and Neurodegeneration

A competition-funded PhD at the MRC Laboratory of Molecular Biology in Cambridge, working out how protein aggregates such as α-synuclein and β-amyloid get into brain cells, why they become toxic and how they spread. Two projects are on offer, and applications are open to students of all nationalities. See more funded PhDs.

To understand and eventually treat neurodegenerative diseases marked by protein aggregates, we need to know how those aggregates build up, how they damage brain cells and how they spread. The McMahon group in the LMB’s Neurobiology Division has two PhD projects tackling these questions.

Project 1: How aggregates get into cells

This project builds on the group’s discovery of a mechanism for aggregate uptake into cells, which they call Aggregation-Dependent Endocytosis (published in Nature Communications). Pilot experiments have already used it to visualise the uptake of size-defined α-synuclein aggregates, and the group has built an assay to quantify protein aggregates in cells. You’ll use these tools to investigate:

• The receptors responsible for aggregate binding
• How aggregate size relates to endocytosis
• The mechanisms underlying aggregate uptake
• Ways the process might be prevented

The work is quantitative, both in cells and in vitro, with scope to move from cell lines into neurons and to test how disease-relevant mutations change uptake mechanisms and pathways.

Project 2: Why ordered assemblies become toxic

This project tests a possible mechanism of toxicity, in which ordered protein assemblies interact with different cellular partners from their monomeric forms. The group has developed methods to study assemblies of target proteins, including α-synuclein and β-amyloid, in vitro and in cells. Using mass spectrometry, you’ll identify their main interaction partners and ask whether sequestering or mis-regulating those partners drives cellular toxicity.

The group has also established a live-cell assay in which light triggers rapid aggregation of a target protein, followed by the recruitment of cellular factors. You’ll combine this with biochemical methods to isolate the relevant membrane compartments and identify the partners associated with them.

What you’ll gain

Both projects give hands-on experience across a range of biochemical techniques, experiments in cultured cell lines and neurons, and structural studies of protein aggregates and their interaction partners.

Funding

Funding is available to applicants of all nationalities through open competition. Most UK students at the LMB are supported by MRC Studentships, which cover University fees and currently pay a tax-free maintenance allowance of £23,248 a year. International students are funded through LMB Scholarships, Gates Cambridge, the Cambridge Trust, the Herchel Smith Fund and other University of Cambridge scholarships, or by studentships from their own country. You’ll be considered automatically for any MRC funding you’re eligible for. Find out more on the LMB funding page.

How to apply

Apply through the University of Cambridge Applicant Portal for the PhD in Biological Science (MRC Laboratory of Molecular Biology), naming Dr McMahon’s group. The deadline for 2027 entry is 8 December 2026. As well as your CV, transcripts and two references, you’ll need to upload the LMB PhD Statement of Interest form. Check the LMB’s how to apply page before you start.