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

摘要程序化分子自组装可用于大规模并行构建纳米级器件。例如，针对疾病细胞的药物活性并根据特定分子线索激活的“智能药物”将具有最小的副作用并改善治疗结果。这样的任务需要分子系统在复杂的环境中自主运行，感知和响应分子事件。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的，而是作为一种纳米级的工程材料。单链DNA分子之间的相互作用由这些分子的线性序列决定，并遵循沃森·克里克碱基配对的规则。相对较低的合成成本和相互作用的可预测性使DNA有别于蛋白质等其他(生物)聚合物，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来指定所需的化学体系。接下来，将这种形式描述编译成可进行实验测试的DNA实现。辅助多链DNA复合体介导了这些信号链之间的相互作用。由于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、数字逻辑甚至算法响应--这项工作提出了一种产生复杂分子行为的强大方法。拟议的研究与一个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一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。将重点放在分子编程的教育上，可能是吸引更多女性本科生进入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和共同PI致力于开发和教授关于合成生物学的新的跨部门课程：电气工程系、计算机科学与工程系和生物工程系正在提供合成生物学的联合课程序列。这些课程构成了发展一个广泛的“分子编程”新教育项目的重要的第一步。该协会还参加了华盛顿大学工程学院的桥梁项目，该项目旨在增加少数族裔和女性在工程学领域的参与度。

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.