Modeling of chemotactic sensing in Dictyostelium

盘基网柄菌趋化传感模型

• 批准号: 7280922
• 负责人: Pablo A. Iglesias
• 金额: $ 40.08万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-09-01 至 2010-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7280922
• 关键词: 1-Phosphatidylinositol 3-Kinase; Accounting; Actins; Amoeba genus; Arthritis; Asthma; Bacteria; Binding; Cells; Cellular Morphology; Chemicals; Chemotactic Factors; Chemotaxis; Computer Simulation; Cytoskeleton; Development; Dictyostelium; Dictyostelium discoideum; Diffusion; Disease; Embryonic Development; Enzymes; Equilibrium; Event; Feedback; Homing; Inflammation; Java; Language; Lipids; Localized; Lymphocyte; Maintenance; Measurable; Measurement; Mechanics; Membrane; Memory; Modeling; Motion; Multiple Sclerosis; Natural Immunity; Online Systems; Organism; Outcome; Output; PTEN gene; Phosphatidylinositols; Physiological Processes; Play; Property; Recruitment Activity; Regulation; Role; Series; Signaling Protein; Source; Stimulus; System; Systems Biology; Testing; Time; Tissues; Wound Healing; angiogenesis; cell type; inorganic phosphate; migration; neurogenesis; phosphoinositide-3,4,5-triphosphate; phosphoinositide-3,4-bisphosphate; polarized cell; polymerization; response; simulation; social

DESCRIPTION (provided by applicant): The ability to sense the direction of external chemical sources and respond by polarizing and migrating toward chemoattractants or away from chemorepellants - chemotaxis - is crucial for proper functioning of single cell organisms, such as bacteria and amoebae, as well as multi-cellular systems. Chemotaxis occurs to some extent in almost every cell type at some time during its development. While the role of chemotaxis in innate immunity has been appreciated for over a century, recent evidence suggests that this fundamental cellular response plays a major role in many aspects of development and tissue maintenance. Normal physiological processes such as lymphocyte homing, angiogenesis, embryogenesis, neurogenesis, and wound healing require accurate migration of specific cells. Inappropriate regulation of chemotaxis plays a role in excessive inflammation and inflammation-related diseases such as asthma, multiple sclerosis, and arthritis. To elucidate the mechanisms which control this dual regulation we need to appreciate how temporal responses triggered by stimulus increments relate to the spatial responses of cells in gradients. We intend to integrate mathematical analysis with quantitative measurements of the temporal and spatial changes in these enzymes to account for lipid levels in latrunculin-treated and polarized cells. To this end we plan to develop a series of mathematical and computational models and to validate them experimentally. Specifically, we propose 1) To determine the role of the complementary regulation of the 3' phosphoinositide enzymes in amplification of the external gradient; 2) To develop an interactive web-based Java applet to illustrate gradient sensing; 3) To characterize the effects on amplification of several positive feedback mechanisms.

描述（由申请人提供）： 感知外部化学源方向并通过偏振和迁移向化学吸引剂或远离化学细胞剂的能力 - 趋化剂 - 对于单细胞生物的正确功能，例如细菌和变形虫，以及多细胞系统至关重要。趋化性在某种程度上在其发育过程中的某个时候几乎每种细胞类型都会发生。虽然趋化性在一个世纪以来一直受到趋于先天免疫的作用，但最近的证据表明，这种基本的细胞反应在发育和组织维持的许多方面都起着重要作用。正常的生理过程，例如淋巴细胞托管，血管生成，胚胎发生，神经发生和伤口愈合需要特定细胞的准确迁移。趋化性的不当调节在过度炎症和与炎症有关的疾病（例如哮喘，多发性硬化症和关节炎）中起作用。 为了阐明控制这对双重调节的机制，我们需要理解刺激增量触发的时间响应与梯度中细胞的空间响应有关。我们打算将数学分析与这些酶中时间和空间变化的定量测量相结合，以说明latrunculin处理和偏振细胞中脂质水平。为此，我们计划开发一系列数学和计算模型，并通过实验验证它们。具体而言，我们建议1）确定3'磷酸肌醇酶在扩增外部梯度中的互补调节的作用； 2）开发基于交互式网络的Java小程序来说明梯度感应； 3）表征对几种积极反馈机制扩增的影响。

项目成果

Tools for analyzing cell shape changes during chemotaxis.

• DOI: 10.1039/c0ib00036a
• 发表时间: 2010-11
• 期刊: Integrative biology : quantitative biosciences from nano to macro
• 作者: Xiong Y;Iglesias PA
• 通讯作者: Iglesias PA

Disrupting microtubule network immobilizes amoeboid chemotactic receptor in the plasma membrane.

• DOI: 10.1016/j.bbamem.2011.02.009
• 发表时间: 2011-06
• 期刊: BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES
• 影响因子: 3.4
• 作者: de Keijzer, S.;Galloway, J.;Harms, G. S.;Devreotes, P. N.;Iglesias, P. A.
• 通讯作者: Iglesias, P. A.