Project Grant 2209388

The National Science Foundation awarded a $276,000 Project Grant to an individual located in Seattle, Washington under the Biological Sciences federal grant program (CFDA 47.074). The two-year award will fund research defining the link between genetic variation in human populations and messenger RNA stability.

The fellow will use high-throughput experimental and computational approaches to identify amino acid motifs that alter mRNA stability. This includes a novel massively parallel knock-in assay in cell culture and a machine learning model. The fellow will then determine critical amino acid residues in newly translated protein chains and ribosomes essential for ribosome stalling through systematic mutations. Finally, the research will apply predictive models and mechanistic insights to define human genetic variants that drive phenotypic changes by altering translation and mRNA stability.

The project aims to establish a novel mechanism by which missense variants alter gene expression and lead to molecular, cellular, and organismal phenotypes. It will provide a framework for predicting functional relevance of single nucleotide variants in the human genome. The award will also support the fellow's training in advanced DNA sequencing and machine learning techniques.