Gradient Tracking and Chemotropism

梯度跟踪和趋化性

基本信息

批准号：
8656373
负责人：
Timothy C Elston
金额：
$ 44.93万
依托单位：
DUKE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2013
资助国家：
美国
起止时间：
2013-05-01 至 2017-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8656373
关键词：
Actins Address Behavior Binding Biological Models Caliber Cell Surface Receptors Cell model Cells Cellular biology Chemicals Chemotactic Factors Chemotaxis Computer Simulation Conceptions Cues Data Detection Disseminated Malignant Neoplasm Eukaryotic Cell Exposure to Failure Feedback Food G-Protein-Coupled Receptors Genetic Goals Growth Home environment Homing Immune Immune system Individual Invaded Ligands Link Location Malignant - descriptor Malignant Neoplasms Masks Mediating Medical Microscopy Molecular Neoplasm Metastasis Nervous system structure Noise Organism Partner in relationship Pathway interactions Pheromone Pheromone Receptors Process Receptor Cell Saccharomyces cerevisiae Sexual Partners Signal Transduction Site Source System Testing Vesicle Yeast Model System Yeasts axon guidance cancer cell design egg fighting insight interest mathematical model mutant novel polarized cell public health relevance receptor receptor binding repaired research study response sperm cell success trafficking tumor wound yeast genetics

Actins Address Behavior Binding Biological Models Caliber Cell Surface Receptors Cell model Cells Cellular biology Chemicals Chemotactic Factors Chemotaxis Computer Simulation Conceptions Cues Data Detection Disseminated Malignant Neoplasm Eukaryotic Cell Exposure to Failure Feedback Food G-Protein-Coupled Receptors Genetic Goals Growth Home environment Homing Immune Immune system Individual Invaded Ligands Link Location Malignant - descriptor Malignant Neoplasms Masks Mediating Medical Microscopy Molecular Neoplasm Metastasis Nervous system structure Noise Organism Partner in relationship Pathway interactions Pheromone Pheromone Receptors Process Receptor Cell Saccharomyces cerevisiae Sexual Partners Signal Transduction Site Source System Testing Vesicle Yeast Model System Yeasts axon guidance cancer cell design egg fighting insight interest mathematical model mutant novel polarized cell public health relevance receptor receptor binding repaired research study response sperm cell success trafficking tumor wound yeast genetics

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项目摘要

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.

描述（由申请人提供）：细胞在检测和跟踪感兴趣的化学品的浅梯度方面非常熟悉。微生物追踪寻找食物或伴侣的梯度，并且类似的过程是神经系统中轴突指导的基础，将免疫细胞归归其为侵略者，将修复细胞爬向伤口部位以及在受孕期间精子向卵子的引导。梯度跟踪也有助于癌症的转移，因此了解细胞如何跟踪浅化学梯度具有医学相关性和基本兴趣。通过细胞表面受体检测化学物质后，细胞要么向信号源移动或生长。在许多情况下，可扩散物质的梯度较浅，导致小细胞直径的微小浓度差异。通过单个受体配体相互作用的随机性使梯度检测变得更加困难，这会导致分子噪声，从而掩盖微小的空间梯度信号。尽管噪声差，允许细胞有效地跟踪甚至非常浅的梯度的机制也很少理解。在此提案中，我们使用独特的酵母模型系统来研究这些机制。在交配过程中，酵母细胞偏振并长大了信息素梯度，以发现并与异性伴侣融合。我们建议将尖端显微镜，遗传学和计算建模的组合结合在一起，以了解酵母细胞跟踪信息素梯度的方式。