Computational genomics approaches to study mechanisms and function of mRNA splicing

Project Summary The overarching goal of this project is to understand how RNA splicing is encoded in DNA sequence and how it impacts biological function and to use this knowledge to help design treatments or drugs to improve human health. Achieving these goals requires a comprehensive and deep characterization of mRNA splicing mechanisms and function, which can only be achieved by developing and applying novel genomic assays, computational approaches, and analytical framework to study mRNA splicing. In this project, we propose to: (i) develop computational methods to facilitate studies of RNA splicing in human biology and disease, (ii) characterize splicing-mediated regulation of gene expression levels, which our preliminary findings indicate is a common mechanism and can redefine our functional view of splicing, (iii) investigate mechanisms of RNA splicing modulation by small molecules. Our project has the potential to significantly advance our understanding of RNA splicing mechanisms and function and will help us leverage mRNA splicing as a target for therapies.