Dr. Paul David Harris’ postdoctoral research in the Department of Biological Chemistry at the Hebrew University of Jerusalem is a collaborative project with the Department of Pharmacology at Penn State College of Medicine. Dr. Harris investigates α-synuclein (α-syn), an intrinsically disordered protein (IDP) that is a major factor in the development of Parkinson’s Disease (PD). IDPs are a class of proteins defined by their high degree of structural flexibility and heterogeneity. Some of them play key roles in promoting degenerative diseases known as proteinopathies. Similar mechanisms seem to be at play in all IDPs–they switch from normal forms promoting healthy physiological function to other forms that promote disease. Dr. Harris studies α-syn as a model for understanding the changes in IDP structures and functions, with the motivation to identify therapeutic modes that could maintain health and inhibit disease development in PD and other proteinopathies.
Dr. Harris began learning advanced fluorescence microscopy, including single molecule methods, during his PhD in Bioscience at Saudi Arabia’s King Abdullah University of Science and Technology, using them to understand the cellular machinery that processes our DNA. He employs similar techniques, as well as more recent ones he has developed in his current research, to understand α-syn’s structure-function behavior. Using these techniques he hopes to identify structural states previously undetected.
Dr. Harris’ work could establish new paradigms for understanding the structure-function relationship in IDPs, hence in proteins that lack stable structures. Importantly, Dr. Harris will strive to understand how IDPs transition from their physiology-promoting forms into the harmful forms that ultimately lead to degenerative diseases.