CAREER: Design and modeling for modular bionanotechnology and citizen science

职业：模块化生物纳米技术和公民科学的设计和建模

• 批准号: 2239518
• 负责人: Petr Sulc
• 金额: $ 55万
• 依托单位: Arizona State University
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-02-01 至 2028-01-31
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2239518&HistoricalAwards=false
• 关键词: CAREER; Design; modeling; modular; bionanotechnology

NONTECHNICAL SUMMARYBionanotechnology is a field that uses designed molecules to construct devices and structures at nanoscale level, with promising applications for the development of novel materials, detection devices, as well as platforms for therapeutics or diagnostics. However, construction of such devices presents significant technical challenges. Computer modeling can provide useful insights into the design mechanisms of such systems. Computer-aided design software is often used in our macroscale world to design e.g. computer chips, cars, planes, etc. so that the device operation can be tested and optimized in simulation first. Construction at the nanoscale however presents multiple challenges. As opposed to our macroworld, nanostructures are typically realized by self-assembly, where individual components randomly diffuse until they meet and assemble into a target structure. To realize more complex structures that would self-assemble in high yields, there is a need for a new simulation framework that can efficiently and, at the same time, accurately represent the assembly and function of such nanostructures. This project will develop a new modeling framework that is capable of simulating self-assembled DNA nanostructures, which currently represent one of the most advanced branches of bionanotechnology. The research team will use this framework to optimize nanostructure assembly for high yield, and computationally design new types of reconfigurable nanostructures. Next, the team will extend the modeling platform to allow for the incorporation of other organic/inorganic molecules and materials, and use it to design a nanoswimmer that can move preferentially in one direction. Overall, this project will facilitate the creation of new nanodevices capable of performing complex tasks that would be difficult to realize experimentally without a sophisticated modeling platform, and bring the field closer to large-scale industrial applications. For the education component of the project, the research team will develop new learning opportunities for university students and the general public. The main effort will involve developing an online citizen science platform, where users can use the simulation platform to design and optimize structures themselves, allowing to crowd-source nanotechnology designs. TECHNICAL SUMMARY:Nucleic acid nanotechnology is one of the most advanced branches of bionanotechnology, with promising applications ranging from biotemplated manufacturing to diagnostics and therapeutics. However, the system sizes (thousands of nucleotides) and the timescales associated with their assembly and function (minutes to hours) make their assembly kinetics very challenging to model. There is hence a pressing need in the field for computational modeling tools that can incorporate additional molecules and materials into the DNA or RNA nanostructures, simulate far-from-equilibrium processes such as ATP-powered motors, and capture nanostructures’ assembly and function over long experimental timescales. To address this challenge, this project will develop a new family of coarse-grained models that can simulate large scale nanosystems, use them to study DNA and RNA nanostructure assembly kinetics, and optimize their designs to improve yields. The PI will use this framework to design new types of DNA and RNA nanostructures with controlled folding pathways that specifically select one possible stable conformation of the molecule, thus creating a reconfigurable biomaterial. Next, the research team will use the modeling platform to design an ATP-powered nanoswimmer that is capable of directional motion.The general framework developed in this project will allow modular design and harness different materials (both organic and inorganic) and functional molecular complexes for nanotechnology construction, thus bringing the field of nanotechnology closer to industry-scale applications and incorporating theoretical modeling into the bionanotechnology design pipeline.The PI’s education program will focus on training undergraduate and graduate students in interdisciplinary research skills required to tackle problems in bionanotechnology harnessing approaches from diverse fields and creating practical hands-on research opportunities as part of the teaching program. Furthermore, this project will develop a citizen science online platform. The platform will use a game-like interface where the players will solve real scientific problems of designing functional DNA nanostructures that will be tested using the developed computer models. It will enable crowd-sourcing the design of nanostructures and hence provide a platform to engage the general public in nanotechnology research.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

非技术摘要Bionanotechnology是一个使用设计的分子在纳米级级别构建设备和结构的领域，并有望在开发新型材料，检测设备以及治疗或诊断平台的开发中应用。但是，此类设备的构建面临着重大的技术挑战。计算机建模可以为此类系统的设计机制提供有用的见解。计算机AID设计软件通常在我们的宏观世界中用于设计，例如计算机芯片，汽车，飞机等，因此可以在模拟中对设备操作进行测试和优化。但是，纳米级的建设提出了多个挑战。与我们的宏观世界相反，纳米结构通常是由自组装实现的，在这些组件中，单个组件随机扩散，直到它们相遇并组装成目标结构为止。为了实现更复杂的结构，这些结构将以高收益为单位，需要一个新的模拟框架，该框架可以有效，同时准确地代表此类纳米结构的组装和功能。该项目将开发一个新的建模框架，该框架能够模拟自组装的DNA纳米结构，该纳米结构目前代表了Biionanotechnology最先进的分支之一。研究团队将使用此框架来优化纳米结构组件的高收益率，并在计算上设计新型的可重构纳米结构。接下来，团队将扩展建模平台，以允许其他有机/无机分子和材料的保险，并使用它来设计一种可以朝着一个方向移动的纳米温材料。总体而言，该项目将有助于创建能够执行复杂任务的新的纳米版，而没有复杂的建模平台，这将很难实现，并使该领域更接近大型工业应用。对于项目的教育部分，研究团队将为大学生和公众开发新的学习机会。主要工作将涉及开发一个在线公民科学平台，用户可以在其中使用仿真平台设计和优化结构本身，从而允许众包纳米技术设计。技术摘要：核酸纳米技术是BiionAnotechnology最先进的分支之一，其实用性从生物塑造制造到诊断和治疗不等。但是，系统尺寸（数千个核动肽）和与它们的组装和功能相关的时间尺度（分钟至小时）使它们的组装动力学对模型非常挑战。因此，该领域的迫切需要计算建模工具，这些工具可以将其他分子和材料纳入DNA或RNA纳米结构，模拟诸如ATP驱动的电动机之类的远程均衡过程，并在长期实验时间内捕获纳米结构的组装和功能。为了应对这一挑战，该项目将开发一个新的粗粒模型家族，可以模拟大型纳米系统，使用它们来研究DNA和RNA纳米结构组装动力学，并优化其设计以提高产量。 PI将使用该框架设计具有控制折叠途径的新型DNA和RNA纳米结构，这些折叠途径专门选择了分子的一种可能的稳定构象，从而创建了可重构的生物材料。接下来，研究团队将使用建模平台设计能够有导向运动的ATP驱动的纳米释放器。该项目中开发的一般框架将允许模块化设计和利用不同的材料（有机和无机和无机性）和功能性分子复合物，以及用于纳米技术结构的纳米技术结构，并将纳米技术的建模纳入了纳米技术的领域。 Pi.PI的教育计划将重点介绍培训本科生和研究生跨学科研究技能，以解决BionAnotechnology中的问题，利用潜水员领域的方法，并创建实际的动手研究机会，作为教学计划的一部分。此外，该项目将开发一个公民科学在线平台。该平台将使用类似游戏的接口，玩家将解决设计功能性DNA纳米结构的真正科学问题，这些问题将使用开发的计算机模型进行测试。它将使众包纳米结构的设计，因此为参与纳米技术研究的公众提供了一个平台。该奖项反映了NSF的法定任务，并通过使用该基金会的知识分子优点和更广泛的影响来审查标准，被认为是通过评估来通过评估来获得的支持。