BIOPHYSICAL MECHANISMS OF CHEMOTAXIS

趋化性的生物物理机制

基本信息

批准号：
7955845
负责人：
ALEXANDER VAN OUDENAARDEN
金额：
$ 2.85万
依托单位：
MASSACHUSETTS INSTITUTE OF TECHNOLOGY
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-06-01 至 2010-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7955845
关键词：
Amoeba genus Biological Models Biomedical Research Cells Chemicals Chemotactic Factors Chemotaxis Computer Retrieval of Information on Scientific Projects Database Cyclic AMP Dictyostelium Dictyostelium discoideum Embryonic Development Eukaryotic Cell Funding Grant Immune response Individuality Institution Lasers Measures Microfluidic Microchips Noise Physiologic pulse Play Population Research Research Personnel Resources Role Signal Transduction Source Techniques United States National Institutes of Health Wound Healing angiogenesis lithography research study response social

Amoeba genus Biological Models Biomedical Research Cells Chemicals Chemotactic Factors Chemotaxis Computer Retrieval of Information on Scientific Projects Database Cyclic AMP Dictyostelium Dictyostelium discoideum Embryonic Development Eukaryotic Cell Funding Grant Immune response Individuality Institution Lasers Measures Microfluidic Microchips Noise Physiologic pulse Play Population Research Research Personnel Resources Role Signal Transduction Source Techniques United States National Institutes of Health Wound Healing angiogenesis lithography research study response social

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项目摘要

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Chemotaxis, the ability of the cell to sense and move in the direction of higher concentration of chemicals, is an integral part of immune response. Additionally it plays a key role in wound healing, angiogenesis, and embryogenesis. Dictyostelium discoideum, a model system for eukaryotic cells, is a social amoeba and has been studied extensively over the past twenty years. In our experiments, we probe and quantitatively measure the initial chemotactic response of single Dictyostelium cells by quantifying the localization dynamics of this key component of signaling transduction network in response to repeated spatio-temporal pulses of chemoattractant. We find that the response of a single cell is very reproducible from pulse-to-pulse. In contrast, we observe a large variability in the chemotactic response from cell-to-cell even when different cells in population are exposed to the same pulse. Although on average a population of cells finds the correct direction of the pulse, a significant variability is observed in the direction and the magnitude of the response. Origins of the noise and cell individuality by quantitatively are explored by measuring the external concentration of the cAMP molecules. We observe that the reliability in the directional sensing mechanism is not limited by the low number of external cAMP molecules and the noise does not decrease when the external cAMP molecules increases by 2 orders of magnitude. Additional studies aimed at better understanding the chemotaxis mechanism will utilize microfluidic devices produced via soft lithography techniques to generate a variety of spatio-temporal chemical gradients.

该副本是利用众多研究子项目之一由NIH/NCRR资助的中心赠款提供的资源。子弹和调查员（PI）可能已经从其他NIH来源获得了主要资金，因此可以在其他清晰的条目中代表。列出的机构是对于中心，这不一定是调查员的机构。趋化性是细胞在化学物质浓度较高的方向上感知和移动的能力，是免疫反应不可或缺的一部分。此外，它在伤口愈合，血管生成和胚胎发生中起关键作用。 Dictyostelium Discoideum是一种真核细胞的模型系统，是一种社交变形虫，在过去的二十年中已经进行了广泛的研究。在我们的实验中，我们通过量化信号转导网络的这一关键成分的定位动力学，以响应重复的化学物质吸收剂的重复时空脉冲来探测和定量测量单个dictyostelium细胞的初始趋化反应。我们发现，单个单元的响应与脉冲之间非常可重现。相比之下，即使在种群中不同的细胞暴露于相同的脉冲时，我们也观察到从细胞到细胞的趋化反应有很大的差异。尽管平均而言，一个细胞群找到了脉搏的正确方向，但在响应的方向和大小上观察到显着的变化。通过测量cAMP分子的外部浓度来探索噪声和细胞个性的起源。我们观察到，定向感应机制的可靠性不受外部cAMP分子数量少的限制，当外部营地分子增加2个数量级时，噪声不会降低。旨在更好地了解趋化机制的其他研究将利用通过软光刻技术生产的微流体设备来生成各种时空化学梯度。