NDC for the Optical Control of Biological Function

用于生物功能光学控制的 NDC

• 批准号: 7254451
• 负责人: Ehud Isacoff
• 金额: $ 118.76万
• 依托单位: UNIVERSITY OF CALIF-LAWRENC BERKELEY LAB
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-09-30 至 2011-09-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7254451
• 关键词: NIH Roadmap Initiative tag; Xenopus oocyte; alcohol phosphotransferase; bioengineering /biomedical engineering; cell surface receptors; genetically modified animals; laboratory mouse; laboratory rat; membrane channels; membrane proteins; method development; molecular probes; nanotechnology; neurophysiology; optics; peptide chemical synthesis; protein protein interaction; protein structure function; serine threonine protein kinase; tissue /cell culture

DESCRIPTION (application abstract) We propose to create an NDC for the Optical Control of Biological Function, to develop methods for rapidly turning select proteins in cells on and off with light. The strategies are broadly applicable across protein classes. The approach will be used for the non-invasive, quantitatively precise, control of the biomolecular dynamics of individual proteins, and for controlling signaling interactions between pairs of proteins. This approach can bring us closer to one of the central goals in biology: that of directly relating molecular events in particular cells to the function of an organ and the behavior of the organism. The developments hold promise in medicine for drug discovery, synthetic biology and the direct treatment of disease. We will develop three technology platforms: 1) chemical and molecular toolkits of modular parts for optical control and chemical integration into proteins, 2) viral delivery for installing photo-switchable proteins into cells, and 3) light delivery systems that make it possible to address these nanodvices in vivo. We will work to solve three engineering and clinical challenges: a) devise a general strategy for optical control over the functional state of individual proteins and the signaling interactions of pairs or groups of proteins; b) gain optical control over the signaling and enzymatic activity of cells in vitro, and c) adapt these approaches to treat retinal and cardiac pathologies. Members of the NDC will be organized into integrated, interdisciplinary teams. We expect three major outcomes. First, rounds of chemical synthesis, genetic engineering and biological testing will help develop the basic design for optical control of protein function, for the specific orthogonal attachment of light-gates, and for the optimal methods of molecular and light delivery in vivo. Second, we will employ light-gated proteins in animal models of human disease. Third, over 5 years we will formulate strategies for applications to cell-based drug screening and remote control switches for synthetic cells, and we will evaluate toxicity to guide the development of biocompatible devices that could be used in the clinic.

描述（应用摘要） 我们建议为生物功能的光学控制创建一个NDC，以开发用于快速用光和关闭细胞中选择蛋白的方法。这些策略在蛋白质类别中广泛适用。该方法将用于对单个蛋白质的生物分子动力学的非侵入性，定量精确的控制，并控制蛋白质对之间的信号相互作用。这种方法可以使我们更接近生物学中的主要目标之一：将特定细胞的分子事件与器官的功能和生物体的行为相关联。这些发展在药物发现，合成生物学和直接治疗疾病的医学方面有希望。 我们将开发三个技术平台：1）模块化零件的化学和分子工具包，用于光学控制和化学整合到蛋白质中，2）病毒递送，用于将可相关的蛋白质安装到细胞中，以及3）轻型递送系统，可以在体内解决这些Nanodvices。我们将努力解决三个工程和临床挑战：a）制定对单个蛋白质功能状态以及对蛋白质或蛋白质组的信号传导相互作用的一般策略； b）对细胞体外的信号传导和酶活性的光学控制以及c）适应这些方法治疗视网膜病理和心脏病理。 NDC的成员将组织成综合的跨学科团队。我们预计三个重大结果。首先，化学合成，基因工程和生物学测试将有助于开发基本的蛋白质功能的设计，用于光门的特定正交附着以及体内分子和光递送的最佳方法。 其次，我们将在人类疾病的动物模型中使用光门控蛋白。第三，在5年以上，我们将制定用于合成细胞的基于细胞的药物筛查和遥控开关的应用策略，我们将评估毒性，以指导可在诊所中使用的生物相容性设备的开发。