Project 1 - Directional Sensing

项目 1 - 方向感测

• 批准号: 8316903
• 负责人: WOUTER-JAN RAPPEL
• 金额: $ 43.24万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-08-15 至 2017-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8316903
• 关键词: Address; Affect; Algorithms; Back; Binding; Caliber; Cells; Chemotactic Factors; Chemotaxis; Computer Simulation; Cyclic AMP; Data; Data Analyses; Dictyostelium discoideum; Exhibits; Kinetics; Ligands; Measures; Membrane; Microfluidic Microchips; Modeling; Mutation; Pathway interactions; Phase; Process; Protocols documentation; Ras Signaling Pathway; Reporter; Resolution; Role; Signal Pathway; Signal Transduction; Source; Spatial Distribution; Stimulus; Testing; Time; Work; experience; novel; receptor; research study; response

Experiments using fluorescent reporters have shown that the spatial distribution of many signaling pathway components is altered following a change in the chemoattractant cAMP concentration. These changes occur during the first 0-10 sec after binding or unbinding of the ligand to the receptors. Within this time frame, the membrane closest to the cAMP source experiences an increase in certain signaling components while other components display an increased concentration at the membrane away from the source. Even though a large number of signaling components have been identified, the precise mechanisms of directional sensing remain unclear. To fully understand these mechanisms it is essential to obtain quantitative data using precisely controlled stimulations. To address these mechanisms, we propose to investigate the initial phase of the chemotaxis process using an approach in which the chemoattractant stimulus can be carefully controlled, both spatially and temporally. The results from these experiments will be integrated into models that, in turn, will guide the experiments. We believe that such interaction of modeling with experimentation is essential for making progress in understanding eukaryotic chemotaxis. Indeed, it is this interaction that has proven to be fruitful during the past 4 years.

使用荧光报告基因的实验表明，许多信号通路成分的空间分布随着趋化剂 cAMP 浓度的变化而改变。这些变化发生在配体与受体结合或解除结合后的前 0-10 秒内。在此时间范围内，最接近 cAMP 源的膜的某些信号成分会增加，而其他成分在远离源的膜上的浓度会增加。尽管已经识别出大量信号成分，但方向感测的精确机制仍不清楚。为了充分理解这些机制，必须使用精确控制的刺激来获取定量数据。为了解决这些机制，我们建议使用一种可以在空间和时间上仔细控制趋化剂刺激的方法来研究趋化过程的初始阶段。这些实验的结果将被整合到模型中，进而指导实验。我们相信，建模与实验的这种相互作用对于在理解真核趋化性方面取得进展至关重要。事实上，这种互动在过去四年中已被证明是卓有成效的。