Grant: Alliance Grants

Living cells carry out many functions, enabled by the activity of molecular machines known as proteins. Protein populations vary between different cell regions, enabling specialized function of these regions. Proteins are encoded by DNA, which is transcribed to messenger RNA (mRNA) that is translated into proteins by ribosomes. While proteins can be targeted to a cell region after translation, recent work shows that much of the cellular organization of proteins is effected by mRNA targeting to the protein target region, with proteins then locally produced from the mRNA. This project will focus on understanding how physical factors such as mRNA degradation, transport, and translation properties control mRNA targeting to an important cellular organelle, the mitochondria. Recent experimental work provides measurements of mitochondrial association for mRNA of thousands of genes and the means to observe how mitochondrial mRNA association changes as aspects of the cell, such as specific transport pathways, are perturbed. This project will develop mathematical modeling to understand and explain how mRNA association with mitochondria is regulated by the cell, by comparing the results of the mathematical models with experimental observations. Mitochondrial dysfunction is tied to diseases including diabetes and cancer, as well as the aging process, and the results of this work may point towards therapeutic targets.