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Center for cellular construction

蜂窝结构中心

基本信息

批准号：
1548297
负责人：
Wallace Marshall
金额：
$ 2400万
依托单位：
University of California-San Francisco
依托单位国家：
美国
项目类别：
Cooperative Agreement
财政年份：
2016
资助国家：
美国
起止时间：
2016-10-01 至 2026-09-30
项目状态：
未结题

来源：
https://www.nsf.gov/awardsearch/showAward?AWD_ID=1548297&HistoricalAwards=false
关键词：
Center cellular construction

项目摘要

The goal of the Center for Cellular Construction is the transformation of the field of cell biology into a quantitative discipline that uses tools from engineering, physical and computer sciences to enable both a greater understanding of the rules that govern cell behavior and the ability to design cells to have useful functions. The Center will 1) develop the practical and computational tools to predict, design and experimentally test the impact on cellular function of designed changes in the internal organization of cells, 2) create the experimental tools for building multicellular and multi-organism structures, and 3) develop living "bioreactors" that will generate products of commercial value. To achieve this vision, integration is required at many levels. Scientists trained in cell biology, physics, engineering, mathematics and computer science will work together, and practical scientists who experiment in the laboratory will work together with computer modelers and theoreticians. In order to develop cellular machines with real-world applications, university researchers will work with their counterparts in commercial companies, and to train a new generation of researchers at undergraduate, graduate and postdoctoral levels in this emerging field, institutions with strong undergraduate programs will work together with research intensive universities and industrial partners to develop new interdisciplinary courses and training methods. The Center will take advantage of "incubator space" at the University of California-San Francisco to encourage the formation of start-up companies. Partnered with UC-San Francisco in this Center are San Francisco State University, UC-Berkeley, Stanford University, IBM Almaden, and the San Francisco Exploratorium. Education and Human Resource Development (including an emphasis on increasing diversity) will be integrated into the Center through multiple activities; high school students and teachers from San Francisco Unified School District and across the Bay Area will be recruited to participate in summer instructional "Boot Camp" experiences, and 10-20 undergraduate research internships will be offered to students (especially under-represented minorities) from San Francisco State University, City College of San Francisco, and UC Santa Cruz. Public engagement with Center activities will involve Science Festivals, Maker Faires, Hackathons and (through partnership with the Exploratorium) Science Museum Exhibits. The Center will focus on five projects, from basic research to real-world applications, integrated to permit the Center to implement iterative "design-build-test" cycles of living cellular machines. The first project, a Cellular Machine Shop/Core, will create an inventory of high throughput and modular tools for cell engineering that will enable the "build" step of the engineering "design, build, test" cycle. A set of core resources and instruments for the Center community will be assembled, including high throughput and quantitative imaging systems, gene synthesis, and next generation sequencing. These will be used to assemble modules for cellular engineering in other Center projects. The second project, Computer Aided Design, will generate tools to implement a computational "design" platform for engineering cells with predictable and desired internal structure, as well as to design multi-cellular structures. The third project will create the molecular tools necessary to program multiple specialized cell types or organisms into multicellular structures capable of executing complex functions. The fourth project "Living Bioreactor" will specify the organization of intracellular and multi-cellular structures to implement new approaches to metabolic engineering by tuning organelle size to improve yield, and by creating multi-layered self-assembling/self-healing multi-kingdom cell aggregates capable of withstanding harsh conditions, resisting contamination, and facilitating harvesting of the desired products. The fifth project "Cell State Inference Engine" will create a software platform for converting images of cells into estimates of cell environment and signaling state, permitting e.g. the use of cells as living sensors of environmental conditions for real-world applications, and also providing a framework for predicting how cells transition between phenotypic states, one of the great challenges in cell biology

细胞构建中心的目标是将细胞生物学领域转变为一门定量学科，利用工程、物理和计算机科学的工具，使人们能够更好地理解控制细胞行为的规则，并设计出具有有用功能的细胞。该中心将1)开发实用和计算工具，以预测、设计和实验测试细胞内部组织设计变化对细胞功能的影响；2)创建实验工具，用于构建多细胞和多生物结构；3)开发可产生商业价值产品的活“生物反应器”。为了实现这一愿景，需要在许多层次上进行集成。在细胞生物学、物理学、工程学、数学和计算机科学方面受过训练的科学家将一起工作，在实验室进行实验的实践科学家将与计算机建模师和理论家一起工作。为了开发具有实际应用的细胞机器，大学研究人员将与商业公司的同行合作，并在这一新兴领域培养新一代的本科生，研究生和博士后水平的研究人员，具有强大本科课程的机构将与研究密集型大学和工业伙伴合作开发新的跨学科课程和培训方法。该中心将利用加州大学旧金山分校（University of California-San Francisco）的“孵化器空间”，鼓励创业公司的成立。与加州大学旧金山分校合作的是旧金山州立大学、加州大学伯克利分校、斯坦福大学、IBM阿尔马登和旧金山探索博物馆。教育和人力资源发展（包括强调增加多样性）将通过多种活动纳入中心；来自旧金山联合学区和整个湾区的高中学生和教师将被招募参加夏季教学“新兵训练营”体验，并将向来自旧金山州立大学、旧金山城市学院和加州大学圣克鲁斯分校的学生（特别是少数族裔）提供10-20个本科研究实习机会。公众参与中心的活动将包括科学节、创客大会、黑客马拉松和（通过与探索馆的合作）科学博物馆展览。该中心将专注于五个项目，从基础研究到实际应用，使中心能够实现活细胞机器的迭代“设计-建造-测试”周期。第一个项目是细胞机器车间/核心，将为细胞工程创建一个高通量和模块化工具的清单，这将使工程“设计、构建、测试”周期的“构建”步骤成为可能。中心社区的一套核心资源和仪器将组装，包括高通量和定量成像系统，基因合成和下一代测序。这些将用于组装其他中心项目的蜂窝工程模块。第二个项目，计算机辅助设计，将生成工具，以实现具有可预测和期望的内部结构的工程细胞的计算“设计”平台，以及设计多细胞结构。第三个项目将创建必要的分子工具，将多种特化细胞类型或生物体编程为能够执行复杂功能的多细胞结构。第四个项目“活生物反应器”将指定细胞内和多细胞结构的组织，通过调整细胞器大小来提高产量，并通过创建多层自组装/自修复的多界细胞聚集体来实现代谢工程的新方法，这些细胞聚集体能够承受恶劣的条件，抵抗污染，并促进所需产品的收获。第五个项目“细胞状态推断引擎”将创建一个软件平台，用于将细胞图像转换为细胞环境和信号状态的估计，例如允许将细胞用作现实世界应用中环境条件的活传感器，并且还提供一个框架来预测细胞如何在表型状态之间转换，这是细胞生物学中的重大挑战之一