Jessica Ponce and Stephanie Haase To Present at Student Seminar on Thursday, 1/28/2016
Jessica Ponce’s Abstract
Dual Roles of Cyclin C in Heart Disease
Cardiovascular disease is the leading cause of death worldwide. The damage inflicted on the myocardium during myocardial infarction (MI) results from (1) hypoxia during ischemia and (2) oxidative damage upon subsequent reperfusion. Despite extensive investigation, the pathophysiology of myocardial injury in response to ischemia is not fully understood. Cyclin C is a coactivator of the Mediator kinase subcomplex which regulates transcription of genes involved in cardiac metabolism, energy homeostasis and responsiveness of the heart to stress. Recent studies have shown Cyclin C to function independent of mediator in regulating stress-induced mitochondrial hyper-fission in yeast in response to oxidative damage. In humans, the constant electrical and mechanical activities of the heart require a continuous energy supply met by a rich stockpile of mitochondria. Additionally, mitochondrial dysfunction increases the pathogenesis in response to ischemia injury. Although studies have shown the effects of mitochondrial dysfunction in heart disease, there is a current gap in knowledge to understand the functional role of Cyclin C in cardiac mitochondria. We hypothesize that injury in response to IR depends on the translocation of Cylinc C from the nucleus to mitochondria where it regulates mitodynamics. Preliminary data demonstrates Cyclin C translocation in response to stress in cardiomyocytes isolated from adult mouse and neonatal rats. The overall goal of this project is to define the mechanisms whereby Cyclin C regulates metabolism, energy homeostasis in heart disease via two functions: regulating mitochondrial dynamics, as well as regulating transcription of crucial mitochondrial genes. These studies will provide new insights into the regulation of cardiac energy metabolism and may yield novel therapeutic strategies for modulating these processes in the settings of heart disease.
Stephanie Haase’s Abstract
Exploring Clock Neuron Activity using the ArcLight fluorescent voltage sensor
Molecular clocks control rhythmic fluctuations in behavior, transcription, and physiology on approximately 24 hour cycles. These circadian rhythms persist in the absence of external light cues and are driven by special clock neurons in both Drosophila and mammals. The interactions of these clock neurons as a network are not fully understood. Previously, changes in clock neuron function that affected circadian rhythmicity were studied primarily through behavioral assays. ArcLight is a powerful tool that will allow characterization of changes to clock neuron function at the cellular level. ArcLight, a fluorescent voltage sensing protein, has allowed the use of optical electrophysiology on clock neurons that traditional electrophysiology cannot access. By expressing ArcLight protein in these neurons, we are able to identify a putative daily rhythm of activity for a subset of these neurons. We are currently working on identifying daily rhythms of other subsets of clock neurons using ArcLight and plan to characterize behavioral mutants at the cellular level in the future.