GENE NETWORKS: FROM MOLECULES TO MECHANISTIC MODELS

基因网络：从分子到机制模型

基本信息

批准号：
7479997
负责人：
GARRETT M ODELL
金额：
$ 117.03万
依托单位：
UNIVERSITY OF WASHINGTON
依托单位国家：
美国
项目类别：
财政年份：
2002
资助国家：
美国
起止时间：
2002-08-01 至 2008-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7479997
关键词：
3-Dimensional Actins Actomyosin Biochemical Biological Biological Phenomena Biology Breeding Budgets Caenorhabditis elegans Case Study Cell Adhesion Molecules Cell Shape Cells Centrosome Class Collaborations Comparative Study Complement Complex Computer Simulation Computer software Computers Computing Methodologies Custom Cytokinesis Cytoskeletal Filaments DNA Sequence Rearrangement Data Development Developmental Cell Biology Direct Costs Drosophila genus Educational Curriculum Educational process of instructing Educational workshop Embryo F-Actin Face Filament Focal Adhesions Funding Gene Expression Genes Genetic Human Individual Intervention Java Laboratories Left Marines Mechanics Medical Membrane Microscope Microscopy Microtubule-Organizing Center Mission Mitotic Modeling Molecular Molecular Genetics Molecular Motors Morphogenesis Motor Neurons Myosin ATPase Myosin Type II Pattern Pattern Formation Phylogenetic Analysis Postdoctoral Fellow Publishing Purpose Recruitment Activity Regulator Genes Research Research Project Grants Scanning Science Scientist Series Shapes Silicon Dioxide Structure Students System Techniques Technology Testing Training Variant Visit Work abstracting base career cell motility computer framework design in vivo mathematical model molecular dynamics mutant network models outreach polarized cell polymerization professor reconstitution research study response simulation success symposium theories tool

项目摘要

Cellular machinery is more complex than any technology humans have understood. Comprehending how this machinery self-assembles and works requires synthesizing interactions between molecular parts of cells into functional mechanistic models, as does the intelligent design of medical interventions. The only tool capable of this synthesis is mathematical models solved on computers. Detailed case studies of particular cell biological phenomena, not abstract rhetoric, will sharpen this tool and prove it'sworth. The proposed center at Friday Harbor Laboratories will assemble a cross-disciplinary group of 14 scientists plus staff with this mission: to combine experiment and theory with computational modeling techniques we have helped pioneer into detailed case studies of genetic networks operating in two different contexts, and to promulgate this approach, and the tools supporting it. The two contexts extend the proposers' current research: 1 .developmental pattern formation (modules of cross-regulatory genes, installed identically in each cell in an embryo, form and stabilize spatio-temporal gene expression patterns causing cell determination); and 2.cytoskeletal dynamics (biochemical and mechanical interactions among major cytoskeletal filament systems, molecular motors, cell adhesion proteins, and their myriad regulators cause cells to reorganize their internal components, move, change shape, and divide). Recruiting long-term salaried post-docs and visiting sabbatical scientists to the center and collaborating with them to make models of these, or other systems they study, will teach them to make and use computational models to comprehend biological complexity. Other outreach activities: 1) Perfecting and publishing computational methods for making and analyzing models of regulatory and cytoskeletal networks; 2) "Hardening" and disseminating our softwarefor building and analyzing gene network models, and for segmenting/visualizing 3D cytoskeletal structure from scanning confocal microscope data; 3) Teaching yearly research apprenticeship courses to recruit biology undergraduates early to careers combining theory, experiment and computation; 4) Hosting teaching workshops and round-table symposia to broadcast the Center's computational modeling successes, facilitate cross-breeding

蜂窝机械比人类所理解的任何技术都要复杂。理解这种机械如何自组成和工作需要分子之间的综合相互作用细胞的一部分变成功能机械模型，医学的智能设计也是如此干预措施。该合成的唯一工具是在计算机上求解的数学模型。特定细胞生物学现象的详细案例研究，而不是抽象的言论，将使这一点工具并证明它是Sworth。拟议的周五港口实验室的中心将组装由14位科学家组成的跨学科小组以及该任务的员工：结合实验和通过计算建模技术的理论，我们帮助开创了详细的案例研究遗传网络在两种不同的情况下运行，并颁布这种方法以及工具支持它。这两种情况扩展了提议者的当前研究：1。开发模式形成（交叉调节基因的模块，在每个细胞中以胚胎形式相同安装并稳定时空基因表达模式，导致细胞测定）；和 2.骨骨骼动力学（主要细胞骨骼丝之间的生化和机械相互作用系统，分子电动机，细胞粘附蛋白及其无数调节剂会导致细胞为重组其内部组件，移动，改变形状和分裂）。长期招募薪水后，并访问休假科学家到该中心，并与他们合作以制作这些模型或他们研究的其他系统将教会他们制作和使用计算模型理解生物学复杂性。其他外展活动：1）完善和出版用于制作和分析调节和细胞骨架网络模型的计算方法； 2） “硬化”并传播我们的软件，用于构建和分析基因网络模型，以及从扫描共聚焦显微镜数据分割/可视化3D细胞骨架结构； 3）教授年度研究学徒课程，以招募生物学本科生。结合理论，实验和计算； 4）举办教学研讨会和圆桌会议座谈会播放中心的计算建模成功，促进交叉繁殖