Grant: Operating Grant

From genes to the production of proteins, there are still a lot for us to learn to uncover the many mysteries in life and diseases. A gene's initial product from its DNA is a long thread of RNA containing various regions in a way like "several to dozens of beads interspersed on a long chain". The beads (called "exons") have to be accurately "spliced" together in a process called "RNA splicing" to produce proteins. During splicing, the combination of the exons can vary according to cell's needs so as to produce up to thousands of proteins with different properties from a single gene, which is called "alternative splicing". Alternative splicing is an important mechanism by which cells can generate a vast pool of proteins to carry out complex functions such as learning and memory. However, if it goes wrong due to genetic mutations, improper exon combinations can be produced and cause human diseases such as spinal muscular atrophy, Frasier's syndrome and dementia. Yet, despite its importance for cell function and its role in diseases, still little is known of how cells splice together the exons accurately in response to changes in its environment (a "signal" as in the project title) and how we can use this process to correct the mutations in human diseases. This research is to uncover the molecular components and mechanisms using our published model system started more than 10 years ago with calcium signals that are critical in almost every cells/tissues to understand how cells choose a proper combination of exons through alternative splicing in general. The knowledge to be obtained will also help us understand how those genetic mutations cause human diseases to provide better diagnosis and even treatment approaches in the future.