Chemotaxis in Dictyostelium discoideum: integrative approach

描述（由申请人提供）：趋化性，其特点是细胞沿着化学梯度定向运动，是许多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。本项目的总体目标是定量研究社会性阿米巴盘齿骨变形虫的趋化性的三个不同阶段，采用新颖的实验和数学模型相结合的方法。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)定向传感：发生在0-10秒时间尺度上的过程，其特征是几个关键信号成分的亚细胞定位，但不涉及细胞骨架的重组。2)稳定前缘和细胞极性的形成：发生在较长时间尺度（10-45秒）的过程，导致细胞区域可以清楚地识别为正面、背面和侧面。极化可以发生在响应梯度，在这种情况下，它是耦合到梯度传感过程，或可以自发地发生。3)运动性（Motility）：极性建立后发生的过程，包括细胞的实际运动、远距离细胞间的通讯和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，它将为我们提供对化学引诱剂刺激的精确控制。我们的研究目的是为了更好地了解真核细胞的趋化性。这一领域的进展将有助于诊断和治疗涉及细胞迁移的医学问题。

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.