Thursday, April 27th, 4:00 pm
Chevron 150
“From monomers to fibrils: Probing the principles governing protein aggregation”
Abstract:
Considerable progress has been made, using experiments and computations, to decipher the general principles governing the formation of oligomers and fibrils of amyloid proteins implicated in diseases. However, identification of the link between protein aggregation and the systems of disease at the molecular level has proved elusive. A variety of intermolecular interactions influence pathways leading from amyloid-forming protein monomers to fibrils. I will discuss ongoing work to systematically investigate the mechanism of protein aggregation, using simulations and basic concepts from physical chemistry, in order to provide insight into this fundamental biophysical process. Critical areas for future research are highlighted.
Friday, April 28th, 2:30 pm
Eberly 206
"Exploring the role of cholesterol in the amyloid cascade and Alzheimer’s disease”
Abstract:
Cholesterol has been conjectured to play a critical role in the amyloid cascade, the aggregation of amyloid-β (Aβ) protein, and the onset of Alzheimer’s disease. The role proposed for cholesterol has typically included the formation of specific protein-cholesterol complexes. In contrast to these prior conjectures, we propose that cholesterol impacts the genesis of Aβ and the amyloid cascade indirectly by inducing liquid-liquid phase separation and the formation of liquid ordered domains. I will explore the full process of Aβ genesis and the critical role of liquid ordered phases induced by cholesterol. Outstanding questions regarding the essential role of cholesterol in the amyloid cascade are identified for future studies.