Ravi Mandla Rose Hills
Understanding the Genetic Regulation and Evolution of Heart Rate
The main goal of my project is to understand, genetically, how differences in heart rate have evolved such that large mammals have slower heart rates than smaller mammals. So far, I have found strong evidence that the activity of the pacemaker ion channel HCN4 in the sinoatrial node (SAN, the hearts natural pacemaker), correlates with the resting heart rate of different species. My central hypothesis for this heart rate scaling phenomenon is that differences in heart rates among different mammalian species are partially determined by sequence changes at HCN4 enhancer elements, non-coding DNA which controls gene expression. However in order for this hypothesis to be true, there must be a difference in the expression of HCN4 in animals which correlates with heart rate, rather than just a difference in protein activity. My goal is to measure the in-vivo levels of HCN4 mRNA in the SAN of many species to determine if a correlation exists between heart rate and mRNA concentration, to motivate further investigation of this hypothesis. Studying this topic will improve our knowledge of how heart function has evolved, eventually shedding light on the regulation of human heart rate with implications for treatment of patients suffering with SAN disease.