Project Grant 2140153

This three-year, five-hundred twenty-three thousand four-hundred sixty-one dollar project grant from the National Science Foundation's Division of Molecular and Cellular Biosciences will fund research into RNA processing in trypanosome mitochondria. The grant was awarded to Seattle Children's Research Institute on April 1, 2022 and will be completed by March 31, 2025.

The project aims to advance understanding of gene expression regulation in trypanosomes, single-celled parasites that alternate between human and insect hosts and require rapid metabolic changes. Researchers will study the distinctive mechanism by which trypanosomal mitochondrial RNA is extensively edited through addition or removal of nucleotides. They will test models of how this editing is differentially controlled across the parasite's life cycle and define factors influencing substrate specificity. Using genetic, biochemical, and chemical approaches, they will also examine dynamic interactions and remodeling of editing components. Overall, the research seeks to reveal new aspects of editing regulation in two developmental forms, including fidelity, substrate determinants, and editosome interactions. The work directly supports the Biological Sciences program's goals of increasing biological knowledge and understanding major problems through basic research.