PRION PROTEIN MISFOLDING, THE STRUCTURAL BIOLOGY OF PRION DI SEASES

The proposal would fund two research workers for 3 years to address fundamental molecular processes associated with Prion diseases, which include CJD in humans and mad-cow disease in cattle. A key feature of this fatal neurodegenerative disease is the accumulation of a small molecule, the prion protein within the brain. The prion protein changes shape in the diseased form and then clumps together to form the insoluble plaques found in the brains of patients with prion disease. It is the ability of the prion protein to change shape and misfold that will be studied. The interaction of the prion protein with physiological levels of the essential mineral copper will also be investigated, looking into how for example copper influences the shape (structure) and misfolding of the prion protein. These studies will inform drug design and assist in the development of medicines for the disease. Prion diseases have similarities with the more prevalent neurodegenerative disease Alzheimer's and knowledge gained in this study will increase our understanding of both diseases.