Neuronal RNA Biology

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Genetic information from our DNA is transcribed to messenger RNA and then translated to produce proteins, the latter forming the complex machinery of our cells. The flow of information, also called gene expression, is regulated at multiple steps to produce diverse cell types, such as brain cells and muscle cells. Moreover, numerous illnesses such as cancer and neurological disorders can arise when gene expression control mechanisms go awry. Thus, a detailed understanding of how gene expression is controlled is important to combat disease and provide a basic understanding of how different cell types emerge from less specialized progenitor cells. Dr. Calarco's research program will develop a deeper understanding of how several specific layers of gene expression contribute to the growth, differentiation, and function of brain cells called neurons. Specifically, his group will study control mechanisms that occur at the co- and post-transcriptional steps of messenger RNA production and maturation. Using the roundworm Caenorhabditis elegans as a tractable model system, his lab will 1) identify factors controlling messenger RNA processing events in tissues and individual neuronal cell types using genetic screening approaches; 2) use high-throughput sequencing-based approaches to determine the impact of genome sequence variation on mRNA processing regulation; 3) use high-throughput genetic interaction screens to identify combinatorial interactions of RNA binding proteins that lead to defects in animal behaviour and neuronal function; and 4) Use fluorescence microscopy to create an atlas of RNA binding protein subcellular localization patterns at single neuron resolution. These objectives will provide fundamental mechanistic insight into how key steps of gene expression impact nervous system development and function. Dr. Calarco's research program will also have implications in regenerative medicine and studying disease by identifying the molecular "players" that orchestrate how cells of the brain are created and maintained, and ultimately how they can malfunction in disease.