EAGER: Modeling DNA Manufacturing Processes Using Extensible Attribute Grammars

这一早期概念探索性研究补助金(AGIRE)项目支持美国国家科学基金会的使命，即通过提高制造业服务的能力、可获得性和可负担性来促进国家健康、繁荣和福利，以支持美国在生命科学领域的领导地位。许多复杂的DNA制造项目的实施对生命科学研究至关重要，需要将从生物样品中提取的现有DNA片段与商业运营商化学合成的新DNA片段相结合。大多数生命科学实验室缺乏必要的计算资源来规划和执行自己所需的复杂制造工作流程，而商业服务不愿执行所需的昂贵、小批量和高度定制的合成。因此，许多生命科学实验室的需求正在超过商业运营商目前的能力。该项目将探索创建一种网络制造系统的潜力，该系统可以使最终用户能够进行定制的DNA制造。这项研究的进展最终将被纳入高度先进的商业运营，以服务于国家生命科学研究界的需求。该项目创造性地将DNA制造作为一个引人注目的领域，以开发实现网络制造所需的概念框架。该项目将使用可扩展的属性文法对DNA制造过程进行建模，该文法捕捉合成过程的结构和性能之间的关系。这一概念突破的力量将通过指定一种特定于领域的编程语言来展示，该语言将允许最终用户定义、分析和执行复杂的DNA制造项目。该语言最初将容纳代表广泛的DNA合成需求的三类项目：1)将合成DNA片段插入现有的质粒中，2)产生代表一组给定DNA构建块的组合组装的质粒库，以及3)编辑酵母菌株的基因组；全基因组工程的例子。该奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。

This EArly-concept Grant for Exploratory Research (EAGER) project supports the NSF mission of advancing the national health, prosperity and welfare by increasing the capabilities, accessibility and affordability of manufacturing services in support of America's leadership in the life sciences. The execution of many complex DNA manufacturing projects essential for life sciences research requires the combination of existing DNA fragments derived from biological samples with new DNA fragments chemically synthesized by commercial operators. Most life science laboratories lack the essential computational resources needed to plan and execute the complex manufacturing workflows required on their own, while commercial services are unwilling to perform the expensive, small batch and highly customized syntheses that are needed. As a result, the demands of many life science laboratories are outrunning the current capabilities of commercial operators. This project will explore the potential for creating a cybermanufacturing system that can make custom DNA fabrication accessible to end-users. Advances from the research will ultimately be incorporated into highly advanced commercial operations to serve the needs of the nation's life sciences research community. The project creatively presents DNA manufacturing as a compelling domain for developing the conceptual framework needed to enable cybermanufacturing. The project will model DNA manufacturing processes using extensible attribute grammars that capture the relationships between the structure and performance of synthesis processes. The power of this conceptual breakthrough will be demonstrated by specifying a domain-specific programming language that will allow end-users to define, analyze, and execute complex DNA manufacturing projects. The language will initially accommodate three classes of projects that represent a broad range of DNA synthesis needs: 1) insertion of a synthetic DNA fragment into an existing plasmid, 2) producing a library of plasmids that represents the combinatorial assembly of a given set of DNA building blocks and 3) editing the genome of yeast strains; an example of whole genome engineering.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.