RUI: Analysis of the molecular, cellular and physiologic regulation of a proton mediated cell-cell signaling event in C. elegans

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Multicellular organisms must coordinate the activity of different cells, tissues, and organs to function effectively and efficiently. Processes with regular timing such as heartbeat, breathing, and digestion require signals to pass between cells in a rapid manner. Understanding the nature of these signals and how they are controlled will provide insight into the physiology of multicellular organisms and may identify the causes of physiologic dysfunction.Recent findings suggest an additional role for protons in biological systems: protons can act as rapid transmitters, or signals, between cells. This project focuses on identifying and characterizing the molecular, cellular and physiologic mechanisms of a proton-mediated cell to cell signal in the roundworm Caenorhabditis elegans. The posterior body contraction, which is the first contraction of the roundworm's periodic digestive motor program, is controlled by a proton-mediated muscle contraction signal. Recent studies suggest that a periodic calcium wave regulates this proton signal. The investigator and undergraduate researchers will identify the mechanism(s) regulating this new form of cell-cell communication by isolating and characterizing posterior body contraction mutants. The investigator's undergraduate research lab has determined that mutation of an evolutionarily conserved sodium-proton exchanger regulatory protein, calcineurin B homologous protein (chp), disrupts the posterior body contraction. In Aim 1, the effect of chp mutation on intestinal pH and calcium physiology will be analyzed. In Aim 2, the mechanism by which chp alters sodium-proton exchange activity will be investigated by testing physical interactions, membrane localization and proton exchange. In Aim 3, additional posterior body contraction mutants will be identified using RNA interference and genetic screening. The project will involve many undergraduates in hands-on, investigative research in teaching and research laboratory settings, preparing them for future biology-related professions, and will introduce new technologies to the local scientific community.