The proposal describes a research strategy and training plan to develop the principal investigator, Mr. Joseph Fischer, throughout his graduate career. Mr. Fischer is currently a graduate student in the Human Genetics Graduate Program at Johns Hopkins University. His long-term goal is to become a principal investigator at a predominately teaching institution, working with circular RNA. In order to accomplish this goal, Mr. Fischer must be successfully trained and develop experience in molecular biology, cellular biology, presentation skills and teaching. Mr. Fischer has assembled a diverse mentorship and collaborative team with expertise in all aspects of molecular and cellular biology in order to achieve his goals. His training and career development plan include formal coursework as well as seminars, lab meetings, and teaching opportunities. The proposed research and training plan will guide Mr. Fischer to a successful career as a graduate student and future endeavors. Circular RNA (circRNA) is a class of non-coding RNAs that is abundantly and dynamically expressed in a diverse range of eukaryotes that has been recently re-discovered with the advancement of RNA-sequencing technologies. Currently, the functional significance of most circRNAs is unknown, however, specific circRNAs have been found to perform various functions such as regulate microRNA activity, sequester protein localization, and act as a scaffold or inhibitor to regulate protein-protein and RNA-protein interactions. While the majority of the past research has been focused on identifying their presence and specific functions, the regulation of their stability remains poorly understood. These circRNAs are highly stable and their enhanced stability may provide additional insights into RNA regulation within cells. The goal of this study is to identify factors and sequence specific features that regulate their stability. Overall, the proposed study will allow us to identify the first known regulator of circRNA stability. Additionally my work has the potential to be applicable to other classes of RNA, and it could help further explain the complex expression and dynamic profiles of RNA.
Although the functions of circular RNAs remains poorly understood, the abundance and dynamic expression warrant further investigation. The goal of this study is to identify regulators of circular RNA stability and determine the specificity based on sequence specific features. The results of this study could lead to a mechanism for degrading circular RNAs and may help better elucidate mechanisms for general RNA clearance in cells.