Chemotaxis in Dictyostelium discoideum: integrative approach

盘基网柄菌的趋化性：综合方法

• 批准号: 7484127
• 负责人: WOUTER-JAN RAPPEL
• 金额: $ 98.02万
• 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 2012-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7484127
• 关键词: Chemotaxis; Dictyostelium; discoideum; integrative; approach

DESCRIPTION (provided by applicant): Chemotaxis, which is characterized by directed movement of cells up a chemical gradient, is a key component in a multitude of biological processes, including neuronal patterning, wound healing, embryogenesis, and angiogenesis. The overall aim of this Program Project is to quantitatively study three distinct stages of chemotaxis in the social amoeba Dictyostelium discoideum using an approach that integrates novel experiments and mathematical modeling. Specifically, we propose to investigate chemotaxis by examining three distinct timescales: 1) Directional sensing: processes that occur on a time scale of 0-10 s and that are characterized by subcellular localization of several key signaling components but do not involve the reorganization of the cytoskeleton. 2) Formation of a stable leading edge and cell polarity: processes that occur on longer timescales (10-45 s) and that lead to cell regions that can clearly be identified as front, back and sides. Polarization can occur in response to a gradient, in which case it is coupled to the gradient sensing process, or can occur spontaneously. 3) Motility: processes that occur after the polarity is established and which include the actual movement of the cell, communication between cells at large distances and the coordinated response of large groups of cells (1-8 minutes). Our approach will rely heavily on the use of microfluidic devices which will provide us with precise control over the chemoattractant stimulus. The goal of our research is to better understand chemotaxis of eukaryotic cells. Advances in this field will benefit diagnosis and treatment of medical problems involving cell migration.

描述（由申请人提供）：趋化性的特征是细胞沿着化学梯度定向运动，是多种生物过程的关键组成部分，包括神经元模式、伤口愈合、胚胎发生和血管生成。 该计划项目的总体目标是采用新颖的实验和数学建模相结合的方法，定量研究社会性变形虫盘基网柄菌趋化性的三个不同阶段。 具体来说，我们建议通过检查三个不同的时间尺度来研究趋化性：1）方向感测：在 0-10 秒的时间尺度上发生的过程，其特征是几个关键信号成分的亚细胞定位，但不涉及信号通路的重组。细胞骨架。 2）稳定前缘和细胞极性的形成：在较长时间尺度（10-45秒）上发生的过程，导致细胞区域可以清楚地识别为正面、背面和侧面。 极化可以响应于梯度而发生，在这种情况下，它与梯度感测过程耦合，或者可以自发地发生。 3）运动性：极性建立后发生的过程，包括细胞的实际运动、远距离细胞之间的通信以及大群细胞的协调反应（1-8分钟）。 我们的方法将在很大程度上依赖于微流体装置的使用，这将为我们提供对化学引诱剂刺激的精确控制。 我们研究的目标是更好地了解真核细胞的趋化性。 该领域的进步将有利于涉及细胞迁移的医疗问题的诊断和治疗。