Alpha-Synuclein Condensates and Synaptic Dysfunction in Parkinson’s Disease

About the Project

Parkinson's disease is the fastest-growing neurodegenerative disorder, with cases projected to more than double by 2050. No disease-modifying treatment strategies exist to date, and mechanistic insights are urgently needed. This PhD studentship, hosted at University College London (UCL), aims to answer how alpha-synuclein (α-syn) condensates affect synapse biology and trigger early neuronal pathology. Biomolecular condensates are dynamic compartments that assemble through phase separation and have recently been implicated in many processes of cellular organisation, such as at the synapse. Importantly, they are one of the first steps when molecular dysfunction may occur, preceding pathological protein aggregation and neurodegeneration. Leveraging recent discoveries from the host lab on the regulation of α-syn condensates by the presynaptic protein VAMP2, the research programme will focus on the role played by α-syn condensates in the organisation and function of synapses and their contribution to the progression of Parkinson’s disease.

Research Aims and Approach

This project integrates advanced human neuronal models, genome engineering, and cutting edge imaging to interrogate α-syn biology at unprecedented resolution.

The student will:

• Dissect the functional consequences of α-syn condensate formation: Using CRISPR/Cas9 genome editing, a suite of engineered human iPSC lines will be generated to enable precise molecular tracking and manipulation.
• Model synaptic dysfunction in human neurons: Differentiation into cortical and dopaminergic neurons will allow interrogation of disease-relevant cell types.
• Integrate collaborative approaches: The project will leverage collaborations with experts in synaptic biology, imaging and Parkinson’s disease within UCL and across partner institutions.

Training Environment

Through this studentship, the candidate will have access to the highly renowned and multidisciplinary research environment at UCL. The candidate will be able to collaborate with specialists in single-molecule microscopy, synaptic function, and neurodegenerative disorders, among other disciplines, such as biophysics.

Candidate Profile

Applicants should hold, or expect to obtain, a first-class or high upper second-class Master’s degree (or equivalent) in neuroscience, biochemistry, or a related discipline. A strong interest in synaptic biology, and molecular mechanisms of disease is essential. Experience with iPSC-derived neurons, genome editing, or advanced imaging is advantageous but not required; intellectual curiosity, technical ambition, and a drive to make meaningful contributions to the field are paramount.