Gradient Tracking and Chemotropism

描述(由申请人提供)：细胞非常擅长检测和跟踪感兴趣的化学物质的浅梯度。微生物追踪寻找食物或配偶的梯度，类似的过程也是神经系统轴突引导、免疫细胞向入侵者归巢、修复细胞向伤口部位爬行以及受孕期间精子向卵子引导的过程。梯度追踪也有助于癌症的转移，因此了解细胞如何追踪浅层化学梯度具有医学意义和基本兴趣。一旦通过细胞表面受体检测到化学物质，细胞要么向信号源移动，要么向信号源生长。在许多情况下，可扩散物质的梯度很浅，导致小细胞直径上的微小浓度差异。由于单个受体-配体相互作用的随机性，使得梯度检测变得更加困难，这导致了可以掩盖微小空间梯度信号的分子噪声。尽管有噪音，但允许细胞有效地跟踪即使是非常浅的梯度的机制还知之甚少。在这项建议中，我们使用独特的易于处理的酵母模型系统来研究这些机制。在交配期间，酵母细胞极化并生长出一种信息素的梯度，以寻找并与异性伴侣融合。我们建议结合使用尖端显微镜、遗传学和计算模型来理解酵母细胞如何跟踪信息素梯度。

DESCRIPTION (provided by applicant): Cells are extraordinarily adept at detecting and tracking shallow gradients of chemicals of interest. Micro-organisms track gradients to find food or mates, and similar processes underlie axon guidance in the nervous system, homing of immune cells towards invaders, crawling of repair cells towards wound sites, and guidance of sperm towards the egg during conception. Gradient tracking also contributes to metastasis in cancer, so understanding how cells track shallow chemical gradients is of medical relevance as well as fundamental interest. Upon detecting chemicals through cell-surface receptors, cells either move or grow towards the source of the signal. In many cases, the gradients of diffusible substances are shallow, resulting in minuscule concentration differences across the diameter of small cells. Gradient detection is made even more difficult by the randomness of individual receptor-ligand interactions, which leads to molecular noise that can mask the tiny spatial gradient signal. The mechanisms that allow cells to efficiently track even very shallow gradients despite noise are poorly understood. In this proposal, we use the uniquely tractable yeast model system to investigate these mechanisms. During mating, yeast cells polarize and grow up a gradient of pheromone to find and fuse with opposite-sex partners. We propose to use a combination of cutting-edge microscopy, genetics, and computational modeling to understand how it is that yeast cells track pheromone gradients.