EAPSI: Characterizing the role of a recently discovered protein in the regulation of calcium signaling and cellular contraction in a model tubular tissue

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Tissues containing cellular tubes are vital components of the human body, found in our airways and blood vessels. Proper response of these tissues to stretch is essential to health, and diseases like asthma result from unregulated contraction. Tissues can respond to stretch and regulate contraction by altering calcium levels inside cells. The spermatheca of the microscopic worm C. elegans provides an excellent model for cellular response to stretch, calcium signaling, and regulation of contraction in a tubular tissue. Many genes acting in the spermatheca are similar to the ones in human cellular tubes, and fluorescent sensors allow study of the tissue in a living, intact animal. This project will advance our understanding of how cellular tubes respond to stretch by examining the role of a recently discovered protein, SPV-1, in the regulation of calcium signaling and cellular contraction. This work will be conducted at the National University of Singapore in collaboration with Dr. Ronen Zaidel-Bar, an expert in cell response to mechanical stimuli and co-discoverer of SPV-1. SPV-1 contains an F-BAR domain that senses membrane curvature, a RhoGAP domain that regulates a GTPase known to affect actomyosin contractility in the tissue, and a domain which binds DAG, a lipid signaling molecule generated by a phospholipase required for proper tissue function. These domains suggest SPV-1 can sense tissue stretch and interact with cellular regulatory and contractile networks, and preliminary evidence supports this. This work will image the calcium sensor GCaMP and fluorescently labeled SPV-1 to investigate how SPV-1 localization affects calcium signaling. Understanding SPV-1's role in this tissue will advance our understanding of the fundamental biology of cellular stretch response, and could open new avenues for therapeutic drug targets and tissue engineering. This NSF EAPSI award is funded in collaboration with the National Research Foundation of Singapore.