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.
