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John CalarcoThrough the process of alternative splicing, multiple messenger RNAs can be generated from precursor transcripts. The evolution of alternative splicing has greatly contributed to the diversification of metazoan transcriptomes, and in some species can generate up to an order of magnitude greater number of transcript isoforms than their repertoire of protein-coding genes. Transcriptome-wide analyses have indicated that alternatively spliced exons are often differentially regulated across tissues and during development, indicative of highly orchestrated yet flexible control mechanisms. However, despite the prevalence and importance of spatio-temporally modulated splicing, there are still many unanswered questions pertaining to how a given exon can be dynamically included or exluded from a transcript. Recent studies of tissue-specific splicing regulators have revealed that these factors regulate networks of alternative splicing events in messenger RNAs transcribed from genes with similar biological functions. A major goal is to understand how these networks of splice variants and the factors controlling them contribute to the development of an organism in conjunction with genes modulated by other transcriptional and post-transcriptional modes of regulation. The nervous system provides an attractive model to study the mechanism and role of tissue- and cell-type specific regulation of alternative splicing because it is composed of diverse neuronal cells that require customized gene regulatory programs to achieve specialized functions. Research in my group focuses on studies of alternative splicing regulatory networks in the developing and mature nervous system using both mammalian systems and C. elegans. We will be pursuing these questions using a combination of biochemical, cell biological, classical and molecular genetic approaches as well as genome-wide analyses. Additionally, we plan on investigating the role of other layers of co- and post-transcriptional gene regulation in nervous system development and function. Contact |
