Scientists know that a protein called amyloid builds-up in the brain of people with Alzheimer’s disease. This protein forms into plaques which surround nerve cells in the brain. Exactly how this build-up of amyloid is toxic to the cell is still unclear and clinical trials of drugs that target these plaques have not yet shown a benefit to symptoms of the disease.
Growing evidence points towards much smaller collections of proteins, called oligomers, playing an important role in the development of Alzheimer’s disease.
In this Major Project, Dr Alfonso De Simone, his team, and several collaborators will attempt to better understand the shape and structure of these oligomers. They will try and discover, how these proteins lead to nerve cell death and whether they can identify regions in which they can be targeted with drugs.
The team will use a cutting-edge approach which has recently been used to shed more light on key proteins implicated in another brain disease, Parkinson’s.
The technique involves examining the short protein oligomers, which are highly unstable, short lived, and notoriously difficult to study. They will first stabilise the amyloid oligomers and then analyse the protein fragments through sophisticated biophysical and computational approaches that will reveal their structure at an atomic level.
The ultimate outcome would be to identify a new way which could reduce or combat amyloid oligomers in Alzheimer’s.