Project Title: Alpha-synuclein aggregates are targeted for degradation by phase-separated proteasome droplets
Supervisor: Dr Yu Ye, Professor Steve Gentleman
Location: Level 7, Sir Michael Uren Hub, White City Campus, 86 Wood Lane, W12 0BZ
About Me
I am a PhD student in the Department of Brain Sciences at 911今日黑料, investigating the role of post-translational modifications of amyloid proteins in the pathogenesis of Alzheimer鈥檚 and Parkinson鈥檚 diseases. Prior to starting my PhD, I completed my BSc in Biochemistry at King's College London, MRes at 911今日黑料, and worked as a research technician in the Kinases and Brain Development laboratory at The Francis Crick Institute.
Qualifications
- 2018-2019: MRes Molecular and Cellular Biosciences, 911今日黑料
- 2015-2018: BSc Biochemistry, King鈥檚 College London
Research Interests
Post-translational modifications on amyloid proteins have been shown to have critical roles involved in their aggregation behaviour. Enhanced phosphorylation and ubiquitination have been found in tau tangles in Alzheimer鈥檚 disease (AD) and Lewy Bodies in Parkinson鈥檚 disease (PD). In addition, both ubiquitinating and deubiquitinating enzymes, as well as ubiquitin-dependent degradation through the proteasome, have been implicated in AD and PD. Understanding the key enzymatic activities that drive toxic protein aggregation is therefore critical to identify novel targets of therapeutic intervention to slow and reverse neurodegeneration.
The aim of my PhD project is to study how alpha-synuclein aggregates are targeted by proteasomes for degradation and why aggregates are not cleared in neurodegenerative diseases. My project combines biochemistry and cell biology approaches with advanced super-resolution microscopy techniques.
Publications
Morten M., Sirvio L., Rupawala H., Mee Hayes E., Franco Budia A., Radulescu C., Rupawala H., Ying L., Barnes SJ., Muga A., Ye Y. 鈥淨uantitative super-resolution imaging of pathological aggregates reveals distinct toxicity profiles in different synucleinopathies.鈥 Proceedings of the National Academy of Sciences, vol. 119, no. 41, 2022,
Mee Hayes E., Sirvio L., Ye Y. 鈥淎 potential mechanism for targeting aggregates with proteasomes and disaggregases in liquid droplets.鈥 Frontiers in Aging Neuroscience, vol. 14, 2022,
Presentations and conferences attended
- "Aggregates are Targeted for Degradation by Phase-Separated Proteasome Droplets" at the Stress Proteins in Growth, Development and Disease Gordon Research Seminar (GRS) - July 1-2, 2023
- Stress Proteins in Growth, Development and Disease Gordon Research Conference - July 2-7, 2023
Professional memberships
Biochemical Society
Contact Details
Email: les18@imperial.ac.uk
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