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

RUI：分析线虫中质子介导的细胞间信号传导事件的分子、细胞和生理调节

• 批准号: 0842830
• 负责人: Maureen Peters
• 金额: $ 36万
• 依托单位: Oberlin College
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-02-15 至 2014-01-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0842830&HistoricalAwards=false
• 关键词: RUI; Analysis; molecular; cellular; physiologic

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.

多细胞生物必须协调不同细胞、组织和器官的活动，才能有效地发挥作用。有规律的过程，如心跳、呼吸和消化，需要信号在细胞之间快速传递。了解这些信号的本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。最近的发现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者或信号。本项目的重点是鉴定和表征质子介导的秀丽隐杆线虫细胞间信号的分子、细胞和生理机制。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质子信号。研究者和本科生研究人员将通过分离和鉴定后体收缩突变体来确定调节这种新形式的细胞-细胞通讯的机制。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Aim 1中，我们将分析chp突变对肠道pH和钙生理的影响。在Aim 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Aim 3中，将使用RNA干扰和基因筛选来鉴定额外的后体收缩突变体。该项目将让许多本科生在教学和研究实验室环境中进行动手、调查研究，为他们将来从事与生物学相关的职业做好准备，并将新技术引入当地科学界。