HCC: Large: Collaborative Research: DNA Machine Builder: Creative molecular-machine design through mass-scale crowdsourcing

HCC：大型：协作研究：DNA Machine Builder：通过大规模众包进行创意分子机器设计

• 批准号: 1213127
• 负责人: Erik Winfree
• 金额: $ 45.77万
• 依托单位: California Institute of Technology
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-09-01 至 2016-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1213127&HistoricalAwards=false
• 关键词: HCC; Large; Collaborative; Research; DNA

This project will develop and evaluate methods by which large numbers of humans, together with computers, can advance the field of synthetic biology by assembling a corpus of creative designs of molecular machines built from DNA segments as well as other molecular structures. Specifically, it will develop a massively-distributed DNA machine construction game that will enable human worldwide collective creativity to be applied to problems ranging from the design of novel self-organizing materials to smart therapeutics that can sense and respond to their environment. The innovative approach is to cast problems of constructing molecular nano-machines with specific functions as a collaborative machine design game governed by the rules of DNA strand interactions. This approach points to a new paradigm for future science, in which a large group of people together with computers work on difficult creative problems, finding solutions that could not be found by computers alone, or by people alone, or without the massive participation of users. If successful, this approach could change science profoundly, with wide-ranging impact on many disciplines including nanotechnology, biochemistry, medicine, and even social and economic behavior analysis. Although the project specifically focuses on games that use DNA strands as principal building blocks of nano-machines, the potential set of applications is large, and encompasses three of the most significant problems facing humanity today. The primary goal of the computer game is to develop and focus collective creativity towards a design space of machines governed by DNA molecular mechanisms. It is currently not known whether this form of sophisticated scientific design creativity can be developed rapidly with non-experts. It is also unknown whether this developed creativity can exceed the current capabilities of the scientific community. This project aims to answer a number of fundamental questions: How does one develop computer games to maximize targeted human design creativity? What are the guiding principles of successful molecular design games? How do we generalize game-development principles to the widest possible range of synthetic biology problems? How can we develop a collective creative design process that outperforms any individual creativity? How do we learn from the way people play the game, and distill their strategies towards stronger automated approaches? The successful outcomes of this project can have a wide ranging impact on health and medicine. One such problem is the design of diagnostic devices and imaging technologies. The game players will work to develop DNA sensors and circuits that can autonomously analyze and interpret the information encoded in a set of molecular disease markers. This approach will enable new devices for multi-analyte testing in low resource settings and will lead to novel medical imaging technologies. Another challenge is design of novel targeted therapeutics, in this case novel RNA-based therapeutics that can autonomously sense and analyze their environment and activate a therapeutic response only where required. A third problem is design of novel materials. This project will develop DNA nanostructures with the potential for the massively parallel self-assembly materials with desired electronic, optical, or chemical properties. These materials will find applications in areas from artificial photosynthesis to biofuels production. This effort will have positive broader impacts for informal science education. The game will reach out to people of all demographic profiles in hope of educating everyone about key molecular research challenges, empowering them to solve important scientific problems, and engaging them in research and science in general. Hopefully, the best scores in these games turn into seminal discoveries with deep impact on people's lives. Also, undergraduates will be involved directly in game development, and a course centered around prototyping of molecular games will be offered. Furthermore, the research team will work with education scientists to develop a new curriculum about DNA and how nature uses molecular mechanisms to achieve function. The curriculum will be anchored around the DNA Machine game and will be piloted in US high schools.

该项目将开发和评估大量人与计算机一起可以通过组装由DNA段以及其他分子结构的分子机器的创意设计来推进合成生物学领域的方法。 具体而言，它将开发出大量的DNA机器构建游戏，该游戏将使人类全球的集体创造力适用于从新颖的自组织材料的设计到可以感知和响应其环境的智能治疗剂的问题。创新的方法是构建具有特定功能的分子纳米机器的问题，作为由DNA链相互作用规则控制的协作机器设计游戏。 这种方法指出了未来科学的新范式，其中一大批人与计算机一起处理了困难的创意问题，找到单独的计算机，单独的人或没有大量参与用户的解决方案。如果成功的话，这种方法可能会深刻地改变科学，并对包括纳米技术，生物化学，医学甚至社会和经济行为分析在内的许多学科产生广泛的影响。尽管该项目专门针对使用DNA链作为纳米机器的主要构件的游戏，但潜在的应用程序集很大，并且包括当今人类面临的三个最重要的问题。 计算机游戏的主要目标是将集体创造力发展为由DNA分子机制控制的机器的设计空间。目前尚不知道这种复杂的科学设计创造力是否可以通过非专家迅速发展。这种发达的创造力是否可以超过科学界的当前能力，这也尚不清楚。该项目旨在回答许多基本问题：如何开发计算机游戏来最大化目标人类设计的创造力？成功的分子设计游戏的指导原则是什么？我们如何将游戏开发原理推广到最广泛的合成生物学问题范围？我们如何开发一个胜过任何个人创造力的集体创意设计过程？我们如何从人们玩游戏的方式中学习，并将其策略提升为更强的自动化方法？ 该项目的成功结果可能会对健康和医学产生广泛的影响。 这样的问题是设计诊断设备和成像技术的设计。游戏玩家将努力开发DNA传感器和电路，这些传感器和电路可以自主分析和解释一组分子疾病标记中编码的信息。这种方法将在低资源设置中实现新的设备，用于多分析物测试，并将导致新颖的医学成像技术。另一个挑战是设计新颖的靶向治疗剂，在这种情况下，基于RNA的新型治疗剂可以自主感知和分析其环境并仅在需要时激活治疗反应。第三个问题是新型材料的设计。该项目将开发DNA纳米结构，具有具有所需电子，光学或化学特性的大规模平行自组装材料的潜力。这些材料将在从人工光合作用到生物燃料生产的区域中找到应用。 这项努力将对非正式科学教育产生积极的广泛影响。 该游戏将与所有人口统计资料的人们接触，希望向所有人提供有关关键分子研究挑战的教育，使他们能够解决重要的科学问题，并将他们参与整体研究和科学。希望这些游戏的最佳成绩变成了对人们生活产生深远影响的开创性发现。此外，本科生将直接参与游戏开发，并将提供围绕分子游戏原型制作的课程。此外，研究团队将与教育科学家合作，开发有关DNA的新课程，以及大自然如何使用分子机制来实现功能。该课程将在DNA机器游戏周围固定，并将在美国高中进行驾驶。

项目成果

Verifying chemical reaction network implementations: A pathway decomposition approach

验证化学反应网络的实现：路径分解方法

• DOI: 10.1016/j.tcs.2017.10.011
• 发表时间: 2017
• 期刊: Theoretical Computer Science
• 影响因子: 1.1
• 作者: Shin, Seung Woo;Thachuk, Chris;Winfree, Erik
• 通讯作者: Winfree, Erik

Effective design principles for leakless strand displacement systems

• DOI: 10.1073/pnas.1806859115
• 发表时间: 2018-12-26
• 期刊: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• 影响因子: 11.1
• 作者: Wang, Boya;Thachuk, Chris;Soloveichik, David
• 通讯作者: Soloveichik, David

Automated sequence-level analysis of kinetics and thermodynamics for domain-level DNA strand-displacement systems

• DOI: 10.1098/rsif.2018.0107
• 发表时间: 2018-12-01
• 期刊: JOURNAL OF THE ROYAL SOCIETY INTERFACE
• 影响因子: 3.9
• 作者: Berleant, Joseph;Berlind, Christopher;Winfree, Erik
• 通讯作者: Winfree, Erik

A domain-level DNA strand displacement reaction enumerator allowing arbitrary non-pseudoknotted secondary structures

• DOI: 10.1098/rsif.2019.0866
• 发表时间: 2020-06-24
• 期刊: JOURNAL OF THE ROYAL SOCIETY INTERFACE
• 影响因子: 3.9
• 作者: Badelt, Stefan;Grun, Casey;Winfree, Erik
• 通讯作者: Winfree, Erik

A General-Purpose CRN-to-DSD Compiler with Formal Verification, Optimization, and Simulation Capabilities

• DOI: 10.1007/978-3-319-66799-7_15
• 发表时间: 2017-01-01
• 期刊: DNA COMPUTING AND MOLECULAR PROGRAMMING
• 作者: Badelt, Stefan;Shin, Seung Woo;Winfree, Erik
• 通讯作者: Winfree, Erik