School of Biological and Chemical Sciences

Ruth Haley

Ruth

PhD student

Email: r.a.haley@qmul.ac.uk

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Project title: Co-Assembly and Ion-Channel Formation of Truncated Amyloid-β Isoforms in Alzheimer's Disease

Summary: Alzheimer’s disease is the fourth most common cause of death in the Western world, after cancer, heart disease and stroke.
It is the most prevalent form of dementia and is characterized by the long-term accumulation of the small peptide, amyloid-β (Aβ), within the brain. The onset of disease is linked to the self-assembly of misfolded Aβ into neurotoxic aggregates and fibres which deposit as extracellular plaques. 

Several naturally-occurring Aβ isoforms are released at the synapse, ranging between 38-43 amino-acids in length. Recent investigations have shown that combinations of different Aβ isoforms can augment or frustrate fibre formation.  My aim is to probe the relative ability for different Aβ isoforms to co-aggregate into a single fibres, and to identify the structural mechanism of co-fibrillisation using biophysical techniques such as AFM, TEM and Cryo-EM. This work will also be complemented by toxicity studies, where electrophysiology and AFM can be used to assess the ability of the aggregates to disrupt neuronal cell membrane integrity and form neurotoxic ion channels. 

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