SHF: Small: Programming Networks of Molecular Interactions Using DNA Strand-Displacement Cascades

SHF：小型：使用 DNA 链置换级联对分子相互作用网络进行编程

• 批准号: 1117143
• 负责人: Georg Seelig
• 金额: $ 43万
• 依托单位: University of Washington
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-07-01 至 2016-06-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1117143&HistoricalAwards=false
• 关键词: SHF; Small; Programming; Networks; Molecular

AbstractProgrammed molecular self-assembly could be used for the massively parallel construction of nanoscale devices. For example,"Smart drugs" that target drug activity to disease cells and activate in response to specific molecular clues would have minimal side effects and improve therapeutic outcomes. Such tasks require molecular systems that operate autonomously in complex environments, sensing and responding to molecular events. This project proposes an approach for the automated construction of programmable molecular systems using DNA. DNA is not used to store genetic information but as a nanoscale engineering material. Interactions between single-stranded DNA molecules are determined by the linear sequence of these molecules and follow the rules of Watson Crick base pairing. The relatively low cost of synthesis and the predictability of interactions set DNA apart from other (bio) polymers such as proteins, and make DNA an ideal substrate for an engineering approach. In this method, a desired chemical system is first specified using the language of chemical reaction networks. Next, this formal description is compiled into an experimentally testable DNA implementation. Auxiliary multi-stranded DNA complexes mediate the interactions between these signal strands. Because the language of chemical reactions can be used to specify a large number of behaviors -- including chemical oscillations, chaos, digital logic and even algorithmic responses -- this work suggests a powerful approach for generating complex molecular behaviors.The proposed research is tightly integrated with an outreach program with two main aims. The first aim is to develop an educational framework that teaches the interdisciplinary skills required to succeed in molecular programming research. The second aim is to leverage this framework to attract and engage students who are not traditionally involved in electrical engineering or computer science research. A strong educational focus on molecular programming could be an important recruiting tool for attracting more women undergraduates to electrical engineering and computer science. To achieve their aims, the PI and co-PI are engaged in developing and teaching a new interdepartmental curriculum on synthetic biology: The departments of Electrical Engineering, Computer Science & Engineering and BioEngineering are offering a joint sequence of classes on synthetic biology. These courses form an important first step towards developing a broad new educational program on "molecular programming". The PI also participates in the College of Engineering BRIDGE program at the University of Washington, which is designed to increase the participation of underrepresented minorities and women in engineering.

摘要 编程分子自组装可用于纳米级器件的大规模并行构建。 例如，“智能药物”将药物活性靶向疾病细胞并响应特定分子线索而激活，其副作用将最小化并改善治疗效果。这些任务需要分子系统在复杂的环境中自主运行，感知并响应分子事件。该项目提出了一种使用 DNA 自动构建可编程分子系统的方法。 DNA不是用来存储遗传信息，而是作为纳米级工程材料。单链 DNA 分子之间的相互作用由这些分子的线性序列决定，并遵循 Watson Crick 碱基配对规则。相对较低的合成成本和相互作用的可预测性使 DNA 与蛋白质等其他（生物）聚合物区分开来，并使 DNA 成为工程方法的理想底物。 在该方法中，首先使用化学反应网络语言指定所需的化学系统。接下来，这个正式描述被编译成可通过实验测试的 DNA 实现。辅助多链 DNA 复合物介导这些信号链之间的相互作用。由于化学反应的语言可用于指定大量行为——包括化学振荡、混沌、数字逻辑甚至算法响应——这项工作提出了一种生成复杂分子行为的强大方法。拟议的研究与具有两个主要目标的推广计划紧密结合。第一个目标是开发一个教育框架，教授分子编程研究成功所需的跨学科技能。 第二个目标是利用这个框架来吸引和吸引传统上不参与电气工程或计算机科学研究的学生。 对分子编程的强烈教育关注可能是吸引更多女性本科生学习电气工程和计算机科学的重要招聘工具。为了实现他们的目标，PI 和 Co-PI 致力于开发和教授新的合成生物学跨系课程：电气工程系、计算机科学与工程系和生物工程系正在提供一系列合成生物学联合课程。这些课程构成了开发“分子编程”广泛的新教育计划的重要第一步。 PI 还参加了华盛顿大学工程学院的 BRIDGE 项目，该项目旨在提高代表性不足的少数族裔和女性在工程领域的参与度。