CAREER: Integrated Microsystems for Synthetic Biology

职业：合成生物学集成微系统

• 批准号: 0846618
• 负责人: Michel Maharbiz
• 金额: $ 40万
• 依托单位: University of California-Berkeley
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-07-01 至 2014-06-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0846618&HistoricalAwards=false
• 关键词: CAREER; Integrated; Microsystems; Synthetic; Biology

"This award is funded under the American Recovery and Reinvestment Act of 2009 (Public Law 111-5)."This proposal aims at establishing the foundational knowledge that will enable us to build synthetic multi-cellular machines. The researchers will design, fabricate and test a series of hybrid systems consisting of genetically modified bacteria, microfabricated arrays of chemical actuators and optical sensing. The broad goal of the technical work is to develop techniques for modulating synthetic signaling pathways in E. coli bacteria using chemical micro-interfaces. Aim 1 will produce a microsystem and a synthetic gene construct in which cells, guided by the microsystem, will express gene expression patterns programmed by the user. Aim 2 expands this by adding coordinated feedback into the microdevices to develop a complete hybrid two-component Turing reaction-diffusion system. Aim 3 then applies the knowledge gained in Aims 1 and 2 to transition the control from a flat culture plate onto a spheroidal assembly of cells resembling a simple multi-cellular system.The long term vision of this work is to design, build and test chemical interface microsystems that dynamically guide gene expression patterns of multi-cellular synthetic biology systems. This will require the development of both the relevant microsystems intended for sensing and communicating with cells and the synthetic gene constructs which respond to these microsystems. The United States today stands on the brink of a technological revolution, much as we did in the mid-20th century when we began to build complex electronic devices. Intellectual MeritThe work presented here employs microtechnology to make a radical paradigm shift away from the standard methods in synthetic biology which rely on homogenous populations of cells. To date, successful synthetic pattern generation has only been achieved by manually placing two different populations of cells on a cell culture plate (sender and receiver cells) and allowing them to communicate. This work intends to change this: by communicating directly with cells programmed to respond, cultures of cells can be made to develop spatial inhomogeneities in gene expression. The ability to create complex spatial patterns of gene expression, (ie. synthetic bacterial differentiation) will enable the fabrication of a new class of organic constructs built from co-operating cell populations in a manner analogous to differentiation schemes in developmental biology. Broad ImpactThe broad impact and outreach plan has five components: 1) K-12 workshops with Poplin Press and Matthew Perry to develop and test GoNano!, a card-based teaching aid for elementary and junior high students, 2) the development of both a new BioMEMS course for graduate students at UC Berkeley, based on a syllabus on which the PI has published, and a new core MEMS course for undergraduates (which, surprisingly, does not exist in EECS at UC Berkeley), 3) leadership involvement in Berkeley?s SUPERB program, of which the PI is an alumnus, 4) student exchange and BioMEMS seminars with Prof. Nelson Sepulveda at the University of Puerto Rico, Mayaguez, 5) leadership and participation in the URM community at Berkeley; the PI served as the president of the Latino Faculty & Staff Association at the University of Michigan and that experience can be applied at Berkeley.

“该奖项是根据 2009 年美国复苏和再投资法案（公法 111-5）提供资金的。”该提案旨在建立基础知识，使我们能够构建合成多细胞机器。研究人员将设计、制造和测试一系列由转基因细菌、化学致动器和光学传感的微制造阵列组成的混合系统。这项技术工作的总体目标是开发利用化学微界面调节大肠杆菌合成信号通路的技术。目标 1 将产生一个微系统和一个合成基因构建体，其中细胞在微系统的引导下将表达由用户编程的基因表达模式。目标 2 通过在微型设备中添加协调反馈来扩展此功能，以开发完整的混合双组件图灵反应扩散系统。然后，目标 3 应用目标 1 和 2 中获得的知识，将控制从平坦的培养板转移到类似于简单多细胞系统的球形细胞组装上。这项工作的长期愿景是设计、构建和测试动态引导多细胞合成生物学系统的基因表达模式的化学界面微系统。这将需要开发用于感知细胞并与细胞通信的相关微系统以及对这些微系统做出反应的合成基因构建体。今天的美国正处于技术革命的边缘，就像我们在 20 世纪中叶开始制造复杂的电子设备时所做的那样。智力优点这里介绍的工作采用微技术，使合成生物学中依赖同质细胞群的标准方法发生了彻底的范式转变。迄今为止，成功的合成模式生成只能通过手动将两种不同的细胞群（发送细胞和接收细胞）手动放置在细胞培养板上并允许它们进行通信来实现。这项工作旨在改变这一点：通过直接与编程响应的细胞通信，可以使细胞培养物产生基因表达的空间不均匀性。创建复杂的基因表达空间模式（即合成细菌分化）的能力将使得能够以类似于发育生物学中的分化方案的方式从协作细胞群构建一类新型有机构建体。广泛的影响广泛的影响和推广计划有五个组成部分：1）与 Poplin Press 和 Matthew Perry 一起举办 K-12 研讨会，开发和测试 GoNano!，这是一种针对中小学生的卡片式教具，2）根据 PI 发布的教学大纲，为加州大学伯克利分校的研究生开发一门新的 BioMEMS 课程，以及为本科生开设一门新的核心 MEMS 课程（令人惊讶的是， 加州大学伯克利分校的 EECS 中不存在），3）领导参与伯克利的 SUPERB 项目（该项目的 PI 是其校友），4）在波多黎各大学马亚圭斯分校与 Nelson Sepulveda 教授进行学生交换和 BioMEMS 研讨会，5）领导和参与伯克利的 URM 社区；该 PI 曾担任密歇根大学拉丁裔教职员工协会主席，这一经验可以在伯克利得到应用。