Talk abstracts
Talk on Tuesday 11:15-11:35am submitted by Jonathan Davis
The Central Dogma of Biology: Lessons From Muscle
Jonathan Davis (Department of Physiology and Cell Biology, The Ohio State University)
Abstract:
I would like to thank the Biophysics students for this opportunity and honor to present my lab’s work and interests. Muscle, one of the most beautiful and simple cellular systems to study scientifically, controls its force production via the small calcium-binding protein, Troponin C (TnC). Based on the rules that govern calcium binding, we have engineered cardiac TnC to bind calcium more tightly or weakly. Weak calcium binding causes early death, whereas we and others have shown, stronger calcium binding has therapeutic potential for many heart diseases with increased health and life span. Thus, modulating the protein (one of the three central pillars of biology) has a large impact on organismal outcomes. Based on our recent discovery that the heart generates its proteins at the sites of protein function (local protein synthesis), we are learning that the RNA (the second pillar of biology) of TnC is shuttled throughout the muscle cells and concentrates where cell growth occurs. Further, there are mechanisms at play in which endogenously expressed mutant TnC RNA in a cell does not seem to be able to generate protein, however, virally delivered does generate protein. Thus, RNA regulation is central to TnC function too. Unlike the vast majority of genes, we have discovered that TnC contains within its DNA (the third pillar of biology) a regulatory sequence that seems to control the ability of mice, rats and possibly us humans, to form viable embryos very early in development. We accidentally discovered this phenomenon by changing the DNA to make a mutant TnC protein and we hypothesize that we unwittingly altered an enhancer/silencer function on other genes. Thus, the study of this tiny calcium binding protein has taught us lessons on how the three central pillars of life work together to ultimately control function.
Keywords: Muscle