A single amyloid fibril floating in a patient’s blood or spinal fluid could reveal whether they have Alzheimer’s, Parkinson’s, or another neurodegenerative disease—if only scientists could read its shape. Current techniques like cryo-electron microscopy (cryoEM) have shown that different amyloid shapes correlate with different diseases, but cryoEM cannot work inside complex fluids such as blood or cerebrospinal fluid. This gap means that structural insights from the lab cannot yet be turned into clinical diagnostic tests for early disease detection. This project aims to build an optical method that “fingerprints” the shape of individual amyloid fibrils directly from patient biofluids, without elaborate sample preparation. If it works, the technique could enable earlier and more accurate diagnosis of neurodegenerative diseases, allowing clinicians to distinguish between conditions that currently look similar until late stages. Beyond diagnostics, the approach could serve as an experimental counterpart to computational tools like AlphaFold, providing real-world structural data from biological samples on demand. The research is primarily fundamental—developing a new optical tool—but its direct path to clinical application makes it unusually close to practical use.
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Neurodegenerative diseases, such as Alzheimer’s and Parkinson’s, are closely connected with the buildup of amyloids—proteins that misfold and clump together into fibrils. Recent advances using cryo-electron microscopy (CryoEM) have provided detailed views of these amyloid fibrils, showing how different shapes of these proteins are linked to different disease outcomes. These findings highlight the importance of identifying amyloid fibrils with varying shapes to diagnose and treat neurodegenerative disorders effectively. However, while CryoEM has been invaluable in revealing the shapes of amyloids, it cannot examine fibrils within complex environments, such as human blood or cerebrospinal fluid. This limitation makes it difficult to turn these structural insights into practical diagnostic tools that can be used for early disease detection in clinical settings. My research aims to overcome this challenge by developing a new optical technique that can analyse the shape of individual amyloid fibrils directly from biofluids like blood or cerebrospinal fluid. This method will be designed to “fingerprint” the specific shapes of amyloids with high precision, without the need for complex sample preparation. By doing so, I aim to enable earlier and more accurate diagnosis of neurodegenerative diseases, building on the structural variations in amyloids that CryoEM has helped uncover. Beyond its use in neurodegenerative diseases, this approach could become a powerful tool in broader protein research. It could serve as an experimental counterpart to computational tools like AlphaFold, offering real-world structural data from biological samples on demand. In summary, my research will connect the dots between structural biology and clinical diagnostics, to understand and diagnose neurodegenerative diseases with unprecedented detail. This work aims to advance both scientific knowledge and practical applications, quickly contributing to better disease management and healthier aging.
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