Grant: Discovery Grants Program - Individual

Osmotic pressure changes cause water to flow across the membranes that encase living cells. Such water fluxes can perturb cell structures and functions. Cells respond by adjusting their content of substances called organic osmolytes (amino acids, sugars etc). This ""osmoregulation"" controls water flow to ensure that cells remain properly hydrated, to stabilize their internal machinery, and to support their continuing growth. The osmoregulatory machinery that modulates bacterial osmolyte content has been described. Now we aim to learn how the osmoregulatory systems of bacterium Escherichia coli are coordinated. We will test the following hypotheses. First, the ProQ protein is an RNA chaperone that regulates the genes encoding osmoregulatory proteins, including ProP and ProU. Second, ProP clusters with other membrane-based osmoregulatory proteins at the ends of E. coli cells, which are rod-shaped. This protein clustering, resulting from specific interactions among cell membrane and ""cell skeleton"" components, is necessary for effective osmoregulation and cell growth. This research is designed to address fundamental biological questions. In addition to elucidating osmoregulatory mechanisms it may show us how bacterial cell structures form and function. It is teaching us how to fully translate genomes, predicting the structures and functions of the encoded RNAs and proteins. It may show us how small RNAs control gene expression. Some E. coli strains promote the health of their human and animal hosts. Other strains cause diseases when they infect intestines, brains, bladders or kidneys. Although our work is not designed to directly address food or water safety problems, or control disease, it will show how osmoregulatory mechanisms help E. coli to survive in food, water and animals, including people. Our discoveries will also apply to cells of other microbes, animals and plants that must tolerate osmotic pressure changes. They include yeasts (used to make bread, beer and wine), plant root and leaf cells (which tolerate drought and saline soils) and kidney cells (which control the hydration of people and animals).