A systems biology approach to understanding protein aggregation and its role in neurodegeneration

Project Leader(s): Carole Proctor
Staff: Ian McKeith, Doug Turnbull, Helen Ardley (Leeds University), Ian Lorimer & Douglas Gray (Ottawa Health Research Institute)
Sponsors: Alzheimer Scotland & Alzheimer Research Trust (I have a fellowship which is supported by both these charities)

Neurodegenerative disorders, such as Alzheimer’s, Parkinson’s and Huntington’s diseases are associated with aggregation of misfolded polypeptide chains which are toxic to the cell.

The causes of neurodegeneration are still largely unknown but many complex and interacting mechanisms are involved. The aim of this project is to use an integrative systems biology approach which complements experimental work with mathematical modelling. Models will be built to examine the cellular pathways involved in maintaining protein homeostasis such as the ubiquitin-proteasome, autophagic, and chaperone systems. 

The models will be validated in collaboration with experimental biologists and clinicians both at Newcastle and from other institutions in the UK and abroad. Using computer simulation, the individual models will be used to answer a number of important questions, such as whether aggregates are neuroprotective or neurotoxic, the role of mitochondrial dysfunction, and the role of oxidative stress.


Dr Carole Proctor

Professor Doug Turnbull
Director of the Wellcome Trust Centre