Lab Research Focus
A major objective of research in Dr. Bedwell’s lab is to understand the mechanistic details of translation termination in eukaryotes. Besides the release factors eRF1 and eRF3, many other cellular components influence the process of translation termination. Surprisingly, sophisticated cellular machineries also regulate the abundance of mRNAs based on the location of stop codons. We are using a combination of genetics, biochemistry, and cell biology in a yeast experimental system to better understand the molecular details of how these processes are carried out.
We are also investigating whether pharmacological agents can be used to suppress premature stop mutations that cause human diseases. Two diseases we are using to study this approach are cystic fibrosis (CF) and a lysosomal storage disease called Hurler syndrome. CF is caused by mutations in the CFTR gene. Roughy 10% of CF patients carry a premature stop mutation in the CFTR gene. We have identified drugs that suppress premature stop mutations in the CFTR gene in various CF experimental systems, including cultured CF cells, a mouse expressing a human CFTR transgene, and even CF patients. We also have evidence that this pharmacological approach can alleviate the biochemical defect that causes Hurler syndrome. We are currently making new knock-in mouse models for both CF and Hurler syndrome to further evaluate the feasibility of this novel therapeutic approach. Ultimately, this approach could be used to treat a broad range of human genetic diseases caused by premature stop mutations.
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