Project 2 - Polarity

项目 2 - 极性

• 批准号: 8316911
• 负责人: Alex Groisman
• 金额: $ 9.48万
• 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
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/8316911
• 关键词: Area; Back; Cell Count; Cell Polarity; Cells; Chemotactic Factors; Chemotaxis; Communication; Computer Simulation; Computer software; Coupled; Custom; Data; Devices; Dictyostelium; Dictyostelium discoideum; Exhibits; Generations; Goals; Guanosine Triphosphate; Image; Kinetics; Lateral; Location; Maintenance; Measurement; Membrane; Microfluidic Microchips; Microfluidics; Modeling; Motion; Nature; Phase; Phototoxicity; Play; Pseudopodia; Resolution; Role; Side; Technology; Time; cell motility; mathematical model; mutant; research study; response; statistics

Following the gradient sensing phase, cells reorganize their internal components into a symmetry-broken configuration, resulting in an elongated cell with a clearly identifiable back, front, and side. This polarized state is coupled to motility through the formation of membrane extensions, pseudopodia, which occur mostly at the front of the cell. Using quantitative measurements on cells that are vertically restricted, we have determined that these pseudopodia are closely correlated with membrane areas ("patches") of increased concentration of activated Ras, Ras-GTP. What remains unclear, however, is the role Ras-GTP plays in restricting the pseudopodia to the front of the cell. Furthermore, the mechanisms for the transient nature of the patches and pseudopodia are unclear. Finally, there is a vigorous and ongoing debate whether new pseudopodia split off existing ones via a specialized fip-splitting mechanism or whether new pseudopodia are created in a stochastic fashion, largely independent of the location of the existing pseudopod. The goal of this project will be to examine the mechanisms of cell polarity using microfluidics technology in combination with modeling efforts. The quantitative results from the experiments will be used to construct mathematical models. Conversely, through specific predictions, these models will guide the experiments. Again, we think that such two-way communication between experiments and modeling is essential in making progress in understanding the role of polarity in chemotaxis.

在梯度传感阶段之后，细胞将其内部组件重组为对称性破裂的构型，从而产生一个细长的细胞，并具有明显的背部，前部和侧面。这种极化状态通过形成膜延伸，假卵形的形成，主要发生在细胞的前部。使用对垂直限制的细胞进行定量测量，我们已经确定这些伪足与激活RAS浓度增加的膜区域（“斑块”）密切相关。然而，尚不清楚的是RAS-GTP在将伪型限制到细胞前部的作用。此外，尚不清楚斑块和伪足的瞬时性质的机制。最后，是否有一场激烈的辩论是通过专门的FIP拆分机制将现有的伪虫分开，还是以随机方式创建新的伪虫，在很大程度上与现有假脚架的位置无关。该项目的目的是使用微流体技术与建模工作一起检查细胞极性的机制。实验的定量结果将用于构建数学模型。相反，通过特定的预测，这些模型将指导实验。同样，我们认为实验与建模之间的这种双向交流对于在理解极性在趋化性中的作用方面取得了必要。