Grant: Operating Grant - Priority Announcement: ALS Canada Research Fund

As we age, we begin to face an onslaught of threats to our health that evolution has not protected us against. Many of these include degenerative diseases such as Alzheimer's disease, Parkinson's disease, and Lou Gehrig's disease. It is up to us to design strategies for slowing, stopping, or reversing the progression of these currently incurable diseases. To do this involves understanding the causes of the disease, which are due fundamentally to proteins behaving badly. We propose to investigate the molecular origins of how proteins malfunction in degenerative disease. Malfunction often involves proteins that have misfolded, or have not been properly regulated or customized for function in the cell. By understanding how these proteins have misfolded, and the structural and functional consequences of their disregulation, we can propose more rational cures for these diseases. We have previously developed a theory that may guide the design of treatments to block misfolding pathways and could help predict the progression of degenerative diseases such as ALS. We propose here to apply our theory and develop new computational studies, in order to improve our understanding of the mechanisms and consequences of protein misfolding, and to rationally predict critical protein targets that would stop the progression of currently fatal, misfolding-related degenerative diseases.