Talk abstracts
Talk on Tuesday 11:35-11:55am submitted by Rengasayee Veeraraghavan
Nanocardiology: A Microscopy-Driven Approach to Cardiac Biology and Physiology
Rengasayee Veeraraghavan (Dept. of Biomedical Engineering, OSU)
Abstract:
Growing evidence indicates that cardiac biology and physiology at cellular through organ scales are governed by the action of proteins organized within nanodomains with specialized ultrastructural properties. Multiple phenomena have been identified, whose function and dysfunction cannot be predicted without accounting for the makeup and behavior of nanodomains. Thus, my laboratory’s investigative approach is grounded in high resolution structural and functional imaging, which is complemented by nanoelectrophysiology (Radwański), functional imaging (Györke) and computational modeling (Weinberg). I will present results from ongoing projects to illustrate how this multi-pronged approach is enabling us to take on biological and physiological questions ranging from basic science to translational.
1) The nuts and bolts of cardiac impulse propagation: Cardiomyocytes are electrically coupled via highly specialized and heterogeneous structures called intercalated disks. Using our novel indirect correlative light and electron microscopy (iCLEM) approach, we are compiling the first-ever quantitative picture of healthy and diseased intercalated disks including ultrastructure and molecular organization from nano- through micro-scales. Computational models built using these predict structure-function relationships underlying cardiac conduction.
2) Multiscale arrhythmia mechanisms in calmodulinopathy: Using a multiscale investigative approach, we have uncovered how the D96V mutation in calmodulin dysregulates NaV1.6 neuronal sodium channel inactivation and structural organization to promote pro-arrhythmic Na+/Ca2+ mishandling.
3) Distributed protein synthesis in cardiac myocytes: Using single molecule RNA visualization and spatial image analysis, we have discovered on-demand synthesis of membrane proteins at deployment sites from local mRNA pools provided by microtubule trafficking. We are now uncovering concurrent synthesis of multiple related proteins within microtranslatomes.
Keywords: Super-resolution Microscopy, Cardiovascular, Arrhythmia