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

摘要程序化分子自组装技术可用于纳米级器件的大规模并行构建。例如，“智能药物”针对疾病细胞的药物活性，并对特定的分子线索作出反应，将具有最小的副作用，并改善治疗效果。这些任务需要分子系统在复杂环境中自主运行，感知和响应分子事件。本项目提出了一种利用DNA自动构建可编程分子系统的方法。DNA不是用来储存遗传信息，而是用作纳米级工程材料。单链DNA分子之间的相互作用是由这些分子的线性序列决定的，并遵循沃森-克里克碱基配对规则。相对较低的合成成本和相互作用的可预测性使DNA与其他（生物）聚合物（如蛋白质）区别开来，并使DNA成为工程方法的理想底物。在这种方法中，首先使用化学反应网络的语言指定所需的化学系统。接下来，这个正式的描述被编译成一个实验上可测试的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。因为化学反应的语言可以用来指定大量的行为——包括化学振荡、混沌、数字逻辑和甚至算法响应——这项工作为生成复杂的分子行为提供了一种强大的方法。拟议的研究与一个有两个主要目标的外展计划紧密结合在一起。第一个目标是建立一个教育框架，教授在分子编程研究中取得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那些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进入电子工程和计算机科学专业的重要招聘工具。为了实现他们的目标，PI和合作PI正致力于开发和教授一门新的合成生物学跨部门课程：电子工程系、计算机科学与工程系和生物工程系正在提供一门关于合成生物学的联合课程。这些课程形成了一个重要的第一步，朝着发展一个广泛的新的教育计划“分子编程”。PI还参加了华盛顿大学的工程学院桥梁项目，该项目旨在增加未被充分代表的少数民族和妇女在工程领域的参与。

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.