Modeling Cell Regulatory Networks

细胞调控网络建模

• 批准号: 7905249
• 负责人: Srinivas Ravi V Iyengar
• 金额: $ 10.77万
• 依托单位: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-01 至 2010-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7905249
• 关键词: Adenylate Cyclase; Adrenergic Receptor; Caliber; Camping; Cell Line; Cell model; Cell physiology; Cells; Cellular Morphology; Characteristics; Complex; Computer Simulation; Coupled; Coupling; Cyclic AMP; Cyclic AMP-Dependent Protein Kinases; Dendrites; Development; Equation; Goals; Guanosine Triphosphate Phosphohydrolases; Kinetics; Length; Ligands; Location; MAPK1 gene; Mitogen Activated Protein Kinase 1; Mitogen-Activated Protein Kinases; Modeling; Movement; Neurons; Pathway interactions; Phosphoric Monoester Hydrolases; Property; Protein Isoforms; Protein Phosphatase 2A Regulatory Subunit PR53; Protein phosphatase; Proteins; Reaction; Regulation; Resolution; Role; Scheme; Signal Pathway; Signal Transduction; Signaling Molecule; Solutions; System; Testing; base; beta-adrenergic receptor; information processing; neuronal cell body; phosphodiesterase 4D; phosphoric diester hydrolase; programs; protein protein interaction; research study; virtual; Adenylate Cyclase; Adrenergic Receptor; Caliber; Camping; Cell Line; Cell model; Cell physiology; Cells; Cellular Morphology; Characteristics; Complex; Computer Simulation; Coupled; Coupling; Cyclic AMP; Cyclic AMP-Dependent Protein Kinases; Dendrites; Development; Equation; Goals; Guanosine Triphosphate Phosphohydrolases; Kinetics; Length; Ligands; Location; MAPK1 gene; Mitogen Activated Protein Kinase 1; Mitogen-Activated Protein Kinases; Modeling; Movement; Neurons; Pathway interactions; Phosphoric Monoester Hydrolases; Property; Protein Isoforms; Protein Phosphatase 2A Regulatory Subunit PR53; Protein phosphatase; Proteins; Reaction; Regulation; Resolution; Role; Scheme; Signal Pathway; Signal Transduction; Signaling Molecule; Solutions; System; Testing; base; beta-adrenergic receptor; information processing; neuronal cell body; phosphodiesterase 4D; phosphoric diester hydrolase; programs; protein protein interaction; research study; virtual

DESCRIPTION (provided by applicant): The overall goal of this project is to develop detailed spatial models of cell signaling networks to understand the origins and dynamics of microdomains of signaling components. We will combine spatially realistic models developed in the program Virtual Cell with experiments to understand the characteristics of microdomains. The proposed project is based on the following central hypothesis: "the dynamics of spatial localization as well as activity of the regulators will contribute to amplitude and location of information flow within the signaling network". To test this hypothesis we have set up a simple network consisting of camp and MAP-kinase 1, 2 pathways in neuronal cells. Using this network we will determine the role of the location, concentrations and activity state of key upstream stimulatory components of the systems in the development of spatially defined domains of activated MAP-kinase 1,2. Specific questions include the effect of varying levels of beta-adrenergic receptor occupancy on the extent of MAP-kinase activation as well as the spatial domains of active MAP-kinase; the effect of varying GTPase activity rates of Gs in the coupling of beta-adrenergic receptor to adenylyl cyclases 5 and 2, and the consequent characteristics of the spatial domains of activated MAP-kinase 1,2 and the effect of varying levels of activation of protein kinase A on the extent and spatial localization of MAP-kinase activity. We will also define the role of negative regulators of the signaling network, such as phosphodiesterases and protein phosphatases in determining the characteristics of the spatial domains of activated MAP-kinases 1,2 We will study the role of cellular morphology in defining spatial domains by analyzing the relationship between the length of dendrites and distance from the cell body as well as the length to breadth ratios of dendrites in determining the spatial domains of activated MAPkinase. From such analysis we hope to define the key criteria involved in determining the characteristics of microdomains of signaling molecules within the cell.

描述（由申请人提供）：该项目的总体目标是开发细胞信号网络的详细空间模型，以了解信号组件的微域的起源和动态。我们将在程序虚拟细胞中开发的空间现实模型与实验，以了解微域的特征。拟议的项目基于以下中心假设：“空间定位的动力学以及调节器的活性将有助于信号网络中信息流的幅度和位置”。为了检验这一假设，我们建立了一个简单的网络，该网络由cAMP和MAP-KINASE 1，2个神经元细胞中的途径组成。使用此网络，我们将确定系统关键上游刺激成分的位置，浓度和活动状态在激活的MAP-激酶1,2的空间定义域的开发中的作用。具体问题包括不同水平的β-肾上腺素能受体占用水平对MAP-激酶激活程度以及活性MAP激酶的空间结构域的影响； GS的不同GTPase活性率在β-肾上腺素能受体与腺苷环酶5和2的耦合中的影响，以及随之而来的激活MAP-激酶1,2的空间域的特征，以及蛋白质激酶A在范围和空间基因酶活性的范围内激活水平的影响。我们还将定义信号网络负面调节因子的作用，例如磷酸二酯酶和蛋白质磷酸酶在确定激活的MAP-激酶空间结构域的特征1,2中，我们将研究细胞形态在空间形态中的作用，通过分析距离树长的长度与距离的长度之间的关系来定义空间域中的作用，以确定态度的长度，以确定面包的长度，以及面包的面包和面包的面包仪的面包。激活的Mapkinase的域。从这种分析中，我们希望定义确定细胞内信号分子微域特征的关键标准。