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）：

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.