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

基本信息

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

项目摘要

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方法，通过这些方法，大量人类与计算机一起可以通过组装由 DNA 片段和其他分子结构构建的分子机器的创意设计语料库来推进合成生物学领域。具体来说，它将开发一种大规模分布式 DNA 机器构建游戏，使人类全球集体创造力能够应用于从新型自组织材料的设计到能够感知和响应环境的智能疗法等问题。创新方法是将构建具有特定功能的分子纳米机器的问题转化为受 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，其中一大群人与计算机一起解决困难的创造性问题，找到仅靠计算机、单独的人或没有用户的大量参与无法找到的解决方案。如果成功，这种方法可能会深刻地改变科学，对许多学科产生广泛的影响，包括纳米技术、生物化学、医学，甚至社会和经济行为分析。尽管该项目特别关注使用 DNA 链作为纳米机器主要构建块的游戏，但潜在的应用范围很大，并且涵盖了当今人类面临的三个最重要的问题。电脑游戏的主要目标是开发并集中集体创造力，以实现由 DNA 分子机制控制的机器设计空间。目前尚不清楚这种复杂的科学设计创造力是否可以由非专家快速开发。这种发达的创造力能否超越科学界目前的能力也是未知数。该项目旨在回答一系列基本问题：如何开发电脑游戏以最大限度地发挥有针对性的人类设计创造力？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则推广到尽可能广泛的合成生物学问题？我们如何才能开发出超越任何个人创造力的集体创意设计流程？我们如何从人们玩游戏的方式中学习，并从他们的策略中提炼出更强大的自动化方法？该项目的成功成果将对健康和医学产生广泛的影响。这样的问题之一是诊断设备和成像技术的设计。游戏玩家将致力于开发 DNA 传感器和电路，能够自动分析和解释一组分子疾病标记中编码的信息。这种方法将使新设备能够在资源匮乏的环境中进行多分析物测试，并将带来新颖的医学成像技术。另一个挑战是新型靶向疗法的设计，在这种情况下，新型基于 RNA 的疗法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，该结构具有大规模并行自组装材料的潜力，具有所需的电子、光学或化学特性。这些材料将在从人工光合作用到生物燃料生产等领域得到应用。这项努力将对非正式科学教育产生更广泛的积极影响。该游戏将面向所有人口统计资料的人们，希望让每个人了解关键的分子研究挑战，使他们能够解决重要的科学问题，并让他们参与一般的研究和科学。希望这些游戏中的最佳成绩能够转化为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，并将提供以分子游戏原型设计为中心的课程。此外，研究团队将与教育科学家合作，开发一门关于DNA以及大自然如何利用分子机制实现功能的新课程。该课程将以 DNA Machine 游戏为基础，并将在美国高中进行试点。

项目成果

期刊论文数量（6）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Effective design principles for leakless strand displacement systems

无泄漏线位移系统的有效设计原则

DOI：
10.1073/pnas.1806859115
发表时间：
2018-12-13
期刊：
Proceedings of the National Academy of Sciences
影响因子：
0
作者：
Boya Wang;Chris Thachuk;A. Ellington;E. Winfree;D. Soloveichik
通讯作者：
D. Soloveichik

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：
2017-10
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

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

域级 DNA 链置换反应计数仪，允许任意非假结二级结构

DOI：
10.1098/rsif.2019.0866
发表时间：
2020-06
期刊：
Journal of The Royal Society Interface
影响因子：
0
作者：
Badelt, Stefan;Grun, Casey;Sarma, Karthik V.;Wolfe, Brian;Shin, Seung Woo;Winfree, Erik
通讯作者：
Winfree, Erik

Verifying chemical reaction network implementations: A bisimulation approach

验证化学反应网络的实现：互模拟方法

DOI：
10.1016/j.tcs.2018.01.002
发表时间：
2018-01
期刊：
Theoretical Computer Science
影响因子：
1.1
作者：
Johnson, Robert;Dong, Qing;Winfree, Erik
通讯作者：
Winfree, Erik

A general-purpose CRN-to-DSD compiler with formal verification, optimization, and simulation capabilities

具有形式验证、优化和模拟功能的通用 CRN 到 DSD 编译器

DOI：
10.1007/978-3-319-66799-7_15
发表时间：
2017-01
期刊：
DNA Computing and Molecular Programming
影响因子：
0
作者：
Badelt, Stefan;Shin, Seung Woo;Johnson, Robert F;Dong, Qing;Thachuk, Chris;Winfree, Erik
通讯作者：
Winfree, Erik