ERASynBio: Intensification of the Synthetic Biology Design Cycle

ERASynBio：合成生物学设计周期的强化

• 批准号: 1445570
• 负责人: George Church
• 金额: $ 33.45万
• 依托单位: Harvard University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-08-01 至 2017-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1445570&HistoricalAwards=false
• 关键词: ERASynBio; Intensification; Synthetic; Biology; Design

This ERASynBio EU-US collaborative project is funded jointly by the NSF Systems and Synthetic Biology Program in BIO/MCB and the Biotechnology, Biochemical and Biomass Engineering Program in ENG/CBET. The project addresses a fundamental need in synthetic biology, namely, how to optimize and reduce the Synthetic Biology design/build/test cycle. The goal is to develop and provide a method for the rapid and comprehensive design of system parts and their functional analysis. The proposed intensification process is derived from the close integration and determination of an informational polymer, DNA or XNA (synthetic DNA variants), and their functional characterization in time and space. To achieve this, the team will develop and implement the IODA technology platform (Integration Of the Determination of DNA-sequence And function) by coupling the available Roche hardware infrastructure of next generation sequencing with in situ and in vitro platforms for characterization of the encoded functions. Work package 4 of the project is spearheaded by Prof. Church from Harvard University. His laboratory's role is to develop a suitable platform for in vitro protein synthesis and enzyme assaying capabilities using a Streptavidin-based protein scaffold for the evolution of new-to-nature enzyme catalytic properties. Part of this concept is that the platform has the capacity to recruit novel co-factors such as organometallic catalysts attached to a biotin group into the protein scaffold. The in vitro creation of focused streptavidin libraries will be screened for metathesis-competent catalysts by generating immobilized fluorescent reaction products. Integration of this process into the IODA platform will enable an automated, high-throughput, synthesis and analytical platform for the screening of evolved protein functions under various reaction conditions. The proposed proof of principle of this technology will generate an artificial enzyme that can carry out the ring-closing metathesis at high efficiency under physiological conditions. The project, if successful, will provide enormously useful tools for the field of synthetic biology. In addition this project offers exceptional training opportunities to students and postdoctoral researchers associated with the project. The technology itself will have direct economic impact with novel instrumentation, and indirect impact derived from the development of novel industrially useful catalysts.

这个Erasynbio EU-US协作项目由BIO/MCB中的NSF Systems和合成生物学计划以及ENG/CBET的生物技术，生化和生物量工程计划共同资助。该项目解决了合成生物学的基本需求，即如何优化和减少合成生物学设计/构建/测试周期。目标是开发并提供一种方法，以快速，全面设计系统零件及其功能分析。提出的强化过程来自信息聚合物，DNA或XNA（合成DNA变体）的紧密整合和确定，及其在时空中的功能表征。为了实现这一目标，团队将通过耦合下一代测序的可用Roche硬件基础架构与原位和体外平台来开发和实施IODA技术平台（DNA序列和功能确定的确定），以表征编码功能。 该项目的工作包4由哈佛大学教授牵头。 他的实验室的作用是使用基于链霉亲蛋白的蛋白质支架来开发适合体外蛋白质合成和酶测定能力的平台，以发展新的酶催化特性。 该概念的一部分是该平台具有招募新型的共同因素，例如附在生物素基团到蛋白质支架中的有机金属催化剂。通过产生固定的荧光反应产物，将筛选浓缩链霉亲和素文库的体外创建，以筛选元理学能力催化剂。 将此过程集成到IODA平台中，将使在各种反应条件下筛选进化蛋白功能的自动化，高通量，合成和分析平台。 提出的该技术原理证明将产生一种人工酶，该酶可以在生理条件下以高效率进行环状序列化。 如果成功的话，该项目将为合成生物学领域提供非常有用的工具。 此外，该项目为与该项目相关的学生和博士后研究人员提供了出色的培训机会。 该技术本身将对新颖的仪器产生直接的经济影响，并从新颖的工业有用催化剂的发展产生的间接影响。