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

多细胞生物必须协调不同细胞、组织和器官的活动，以有效和高效地发挥作用。 具有规律定时的过程，如心跳，呼吸和消化，需要信号以快速的方式在细胞之间传递。 了解这些信号的性质以及它们是如何被控制的，将有助于深入了解多细胞生物的生理学，并可能确定生理功能障碍的原因。最近的研究结果表明，质子在生物系统中的另一个作用：质子可以作为细胞之间的快速传递器或信号。本项目的重点是识别和表征的分子，细胞和生理机制的质子介导的细胞信号在线虫小杆线虫。后体收缩是蛔虫周期性消化运动程序的第一次收缩，由质子介导的肌肉收缩信号控制。最近的研究表明，周期性钙波调节这种质子信号。研究人员和本科生研究人员将通过分离和表征后体收缩突变体来确定调节这种新形式的细胞间通讯的机制。 研究者的本科研究实验室已经确定，进化上保守的钠质子交换调节蛋白，钙调神经磷酸酶B同源蛋白（chp）的突变，破坏了后体收缩。在目的1中，将分析chp突变对肠道pH和钙生理学的影响。 在目标2中，chp改变钠-质子交换活性的机制将通过测试物理相互作用、膜定位和质子交换来研究。 在目标3中，将使用RNA干扰和遗传筛选鉴定额外的后体收缩突变体。该项目将涉及许多本科生在实践中，在教学和研究实验室设置的调查研究，为他们未来的生物学相关专业做好准备，并将介绍新技术，以当地的科学界。

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.