Alzheimer’s disease has a profound impact on healthy ageing. It is characterized by the accumulation of a small neuro-toxic peptide, amyloid-beta (Aβ) which forms fibrous plaques within the brain. The mechanism by which Aβ is toxic to neuron is not well understood, however its ability to disrupt membrane integrity and cellular homeostasis is believed to be central to Alzheimer’s disease pathology. The PhD student will use a large tool-kit of biophysical, imaging and spectroscopic techniques to probe lipid membrane interactions. Understanding how Aβ-assemblies interact with cellular membranes is the first step to designing inhibitors to Aβ induced membrane disruption.
 Ion Channel Formation by Amyloid-β42 Oligomers but not Amyloid-β40 in Cellular Membranes
DC Bode, MD Baker, JH Viles (2017) Journal of Biological Chemistry 292, 1404-1413
 Amyloid-β oligomers have a profound detergent-like effect on lipid membrane bilayers, imaged by atomic force and electron microscopy
DC Bode, M Freeley, J Nield, M Palma, JH Viles
(2019) Journal of Biological Chemistry 294, 7566-7572
 Cu2+ accentuates distinct misfolding of Abeta(1-40) and Abeta(1-42) peptides, and potentiates membrane disruption.
CJ Matheou; ND Younan; JH Viles (2015) Biochem J. 466, 233-242
 N-Terminally Truncated Amyloid‐β (11‐40/42) Co‐Fibrillises with its Full‐Length Counterpart, Implications for Alzheimer’s Disease
JD Barritt, ND Younan, JH Viles (2017) Angewandte Chemie 129, 9948–9951
 Lipid bilayer composition modulates the unfolding free energy of a knotted alpha-helical membrane protein. MR Sanders, HE Findlay, PJ Booth (2018). Proc Natl Acad Sci USA 115: E1799-E1808.