Cellular Control:Synthetic Signaling/Motility (RMI)

细胞控制：合成信号/运动 (RMI)

基本信息

批准号：
7498981
负责人：
WENDELL A LIM
金额：
$ 461万
依托单位：
UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
依托单位国家：
美国
项目类别：
财政年份：
2004
资助国家：
美国
起止时间：
2004-09-30 至 2010-09-29
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7498981
关键词：
Acids Actins Adopted Area Back Bacteria Behavior Binding Biologic Characteristic Biological Biological Assay Biological Process Biology Biomedical Engineering Breathing Calculi Cardiovascular system Cell Shape Cell physiology Cells Chemotactic Factors Chemotaxis Class Compatible Complement Complex Computer Simulation Computers Cytoplasm Cytoskeleton Development Devices Discipline Electrical Engineering Electronics Elements Endocrine Endocytosis Engineering Escherichia coli Eukaryotic Cell Event Evolution Excision Feedback Figs - dietary Foundations Generations Genomics Glossary Goals Guanosine Triphosphate Phosphohydrolases Hand Healthcare Hormonal Immune Immune response Immune system In Vitro Individual Invasive Knock-out Knowledge Lead Lesion Life Ligands Link Lipids Listeria Listeria monocytogenes Localized Location Logic Measures Mechanics Mediating Medical Membrane Metabolic Methods Microscopic Modeling Molecular Movement Mutation Myosin ATPase Natural regeneration Neoplasm Metastasis Nerve Neurons Numbers Organelles Organism Outcome Output Patients Pattern Phagocytosis Philosophy Phosphoric Monoester Hydrolases Phosphotransferases Play Polymers Principal Investigator Process Property Proteins Proteomics Quantum Dots Range Reagent Regulation Research Infrastructure Role Salmonella Scientist Shapes Shigella Signal Transduction Signaling Molecule Solutions Specific qualifier value Standards of Weights and Measures Structure System Systems Biology Tail Technology Tertiary Protein Structure Testing Therapeutic Time Transistors Vision Work Wound Healing axon guidance base biological research cell behavior cell motility cellular engineering computerized data processing design driving force experience in vivo information gathering insight interest macromolecule member microbial molecular assembly/self assembly motor control nanocrystal nanodevice nanomaterials nanomedicine nanoparticle nanoscale nanosystems neoplastic cell neutrophil particle pathogen polymerization precursor cell programs receptor repaired response rho rho GTP-Binding Proteins self assembly self organization sensor synthetic biology tumor tumor growth

项目摘要

Our long term goal is to be able to engineer cells or cell-like molecular assemblies that perform "smart" therapeutic functions: tasks such as tissue repair or "search and deliver" actions to treat microscopic tumors or cardiovascular lesions. The ability to precisely engineer cell-based therapeutics would have revolutionary effects on healthcare. Our ability to engineer cells, however, is extremely primitive; achieving this vision will require an understanding of the design principles underlying biological regulatory systems, as well as establishment of a standardized, modular framework of molecular components that can be used to rapidly and reliably fabricate diverse control circuits and assemblies. Once established, such a framework could be used to generate a wide range of cellular behaviors. The goal of our Center is to establish a framework for engineering eukaryotic cells. We have chosen to initially focus on one testbed system: actin-based cell movement. Motility is a complex process driven by molecular self-organization. It is essential during development, wound healing, immune response, and many other processes. The ability to control the movement and targeting of cells would have many therapeutic applications. To lay the foundation for facile engineering of nanoscale motility systems we will develop three technology platforms: 1) a molecular toolkit of modular parts and devices, 2) quantitative assays for analysis of cell polarization, force generation, and movement, and 3) a theoretical frame-work for design of motility circuits. We will develop and refine these platforms by using them to solve four target engineering Grand Challenges: a) Replace or rewire the guidance system in a motile cell. b) Reprogram a non-motile cell to display directed movement. c) Build alternative force generating systems from non-actin polymers and/or nanoparticle assemblies. d) Build cell-like assemblies capable of induced shape change and/or movement. Members of the Center will be organized into integrated, interdisciplinary, interlab teams centered around each of these Grand Challenges. We expect three outcomes. First, cycles of design/fabrication/analysis will help uncover the basic design principles of cell motility circuits. Second, each of these increasingly difficult challenges is a stepping stone on the path toward the engineering of therapeutic cells. Third, the technologies and basic design principles that emerge by tackling these challenges can then be applied to the engineering of many other complex biological processes driven by dynamic self-organization.

我们的长期目标是能够设计执行“智能”治疗功能的细胞或类似细胞的分子组件：诸如组织修复或“搜索并提供”操作以治疗微观肿瘤或心血管病变。精确设计基于细胞的治疗的能力将对医疗保健产生革命性的影响。但是，我们设计细胞的能力极为原始。实现这一愿景将需要了解生物调节系统的设计原理，并建立一个标准化的分子组件模块化框架，这些框架可用于快速且可靠地构建各种控制电路和组件。建立后，可以使用这样的框架来产生广泛的细胞行为。我们中心的目的是为工程真核细胞建立一个框架。我们选择最初专注于一个测试床系统：基于肌动蛋白的细胞运动。运动性是由分子自组织驱动的复杂过程。它在发育，伤口愈合，免疫反应和许多其他过程中至关重要。控制细胞运动和靶向的能力将具有许多治疗应用。为了奠定纳米级运动系统的便利工程基础，我们将开发三个技术平台：1）模块化零件和设备的分子工具包，2）用于分析细胞极化，力产生和运动的定量测定，以及3）一个理论框架工作，用于设计运动通道。我们将通过使用它们解决四个目标工程挑战来开发和完善这些平台：a）替换或重新连接运动单元中的指导系统。 b）重新编程非运动单元以显示有向运动。 c）从非肌动蛋白聚合物和/或纳米颗粒组件中构建替代力生成系统。 d）构建能够诱导形状变化和/或运动的细胞状组件。该中心的成员将被组织成综合的，跨学科的Interlab团队，围绕这些巨大的挑战。我们期望三个结果。首先，设计/制造/分析的周期将有助于揭示细胞运动电路的基本设计原理。其次，这些日益困难的挑战中的每一个都是在通往治疗细胞工程的路径上的垫脚石。第三，通过应对这些挑战而出现的技术和基本设计原理可以应用于由动态自我组织驱动的许多其他复杂生物学过程的工程。