School Colloquia Series - Louise Browne - Dynamics, Disease, and Diamonds: Probing Biology Using Unpaired Electrons
Dynamics, Disease, and Diamonds: Probing Biology Using Unpaired Electrons
Bio: Dr Louise Brown is Senior Lecturer in the Department of Molecular Sciences at Macquarie University. Her research interests are in the protein structural biology field, with a focus on using ‘spin-labels’ to determine structure and dynamics of large protein complexes found in the body. She has pursued new spin-based tools to look at these more challenging biological systems; and recently, co-founded a start-up company – LuciGem.
Abstract: Most key physiological processes in the body are controlled by large, multi-protein complexes with moving parts that respond to external stimuli. In this talk, I will present our efforts to understand the structure and dynamics of one such system – Troponin. The Troponin complex is the switch used to control both heart and skeletal muscle contraction in the body; switching on the muscle in response to calcium binding. Malfunctions in the Troponin complex can lead to deadly consequences including heart failure. For such an important protein, our understanding of its structure is far from complete. While X-ray crystallography and electron microscopy can provide beautiful maps of the protein, the images still only show it to be ‘stuck’ in one state. Tools able to report on dynamics and movement are then needed.
In order to build a molecular movie of the Troponin complex during muscle regulation, our group have largely relied on spectroscopic methods that use reporter group techniques. These include electron paramagnetic resonance (EPR) and nuclear magnetic resonance (NMR). Key to the success of both these approaches is tagging of the protein with a free radical spin-label. Together, the complementary approaches of EPR and NMR have allowed us to rapidly assess the effects of disease causing mutations on the structure and dynamic of Troponin, providing opportunities for rational drug design.
Lastly, in the constant search for better spin-probes, namely those with more stable unpaired electron based systems; our group have been working on optimising nanodiamond materials for probing and manipulating nanoscale bio-systems. I will discuss how our nanodiamond research has led us to dabble in the ‘start-up’ community.