Identifying Novel Therapeutics for the Treatment of Alpha-Synucleinopathies: A Chemistry-Biology Approach to Parkinson's Disease
About the Project
The Clinical Challenge: Parkinson's Disease and Protein Aggregation
Parkinson's disease affects approximately 150,000 people in the UK and accounts for around 8,000 deaths annually. It is the second most common neurodegenerative disorder worldwide, and its prevalence is rising sharply with an ageing population. Yet despite decades of research, treatments remain purely symptomatic — no disease-modifying therapy currently exists that can slow or halt neurodegeneration.
A defining molecular hallmark of Parkinson's disease, and a broader class of disorders known as alpha-synucleinopathies, is the pathological aggregation of the protein alpha-synuclein within neurons. Under normal conditions, alpha-synuclein is a soluble, intrinsically disordered protein involved in synaptic vesicle regulation. In disease, it misfolds and assembles into toxic oligomers and fibrillar aggregates — collectively termed Lewy bodies and Lewy neurites — which propagate through neural circuits and drive progressive cell death. Targeting this aggregation process directly represents one of the most promising, yet largely unrealised, therapeutic strategies in neurodegeneration.
Our Approach: Novel Screening Meets Precision Chemistry
This project capitalises on a uniquely powerful combination: a novel suite of alpha-synuclein aggregation screening assays developed by the supervisory team, integrated with state-of-the-art continuous flow synthetic chemistry for rapid compound optimisation.
Training and Skills Development
This is a genuinely interdisciplinary project and will provide the student with a uniquely broad skill set spanning chemistry and neuroscience. Training will include: Continuous flow chemistry and medicinal/organic synthesis; Protein biochemistry: recombinant protein expression, aggregation assays, FRET-based detection; Cell biology: iPSC-derived neuronal cultures, quantitative imaging, in vitro toxicity profiling; Human tissue handling and neuropathology: brain tissue sectioning, immunofluorescence, imaging mass spectrometry; Drug discovery principles: hit identification, SAR analysis, lead optimisation.
Ideal Candidate Profile
We welcome applications from motivated graduates holding a strong degree (2:1 or above) in Chemistry, Medicinal Chemistry, Chemical Biology, Biochemistry, Neuroscience, or a closely related discipline.
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