CAREER: Engineering Nucleic Acid Devices

职业：工程核酸装置

• 批准号: 0448835
• 负责人: Niles Pierce
• 金额: $ 40万
• 依托单位: California Institute of Technology
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-03-15 至 2011-02-28
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0448835&HistoricalAwards=false
• 关键词: CAREER; Engineering; Nucleic; Acid; Devices

The Pierce Lab at Caltech proposes a research program that combines theoretical, computationaland experimental components to advance the field of structural nucleic acid nanotechnology in developing rigorous and robust methods for encoding arbitrary mechanical function in nucleic acid sequences. Modeling and algorithm development projects will address key analysis and design challenges. The investigation of pseudoknot biophysics will help to create a physically based potential for partition function algorithms and illuminate the role of topology in the behavior of the "kissing hairpin" mechanism under experimental study for catalytic fuel delivery to autonomous devices as well as:-on implementing an efficient hierarchical mutation algorithm for optimizing affinity and specificity for target secondary structures using partition function information-on methods for identifying and designing multiple features of an energy landscape including networks of metastable states relevant to autonomous device design-and on formulating and optimizing the multi-objective design problem that characterizes device engineering, in which multiple strands must conditionally adopt different structures depending on the subsets of strand species that are present.Intellectual MeritThe proposed research program seeks to develop analysis and design tools that will dramatically increase the level of rigor, accuracy, and automation with which nucleic acid devices are engineered. The work encompasses physical modeling, algorithm development, mechanism design, and experimental validation, with the unifying goal of enabling the manipulation of subtle features in the multiple energy landscapes that underlie the design of devices with many conditionally stable states. The development of a practical catalytic fuel delivery method and subsequent construction of a robust autonomous walker that can take hundreds of unassisted steps would represent a breakthrough in the field. Likewise, HCR provides a new functional paradigm for nucleic acid nanotechnology, creating many attractive avenues for investigation.Broader ImpactThe ability to engineer autonomous devices at the nanometer length scale may someday have importantmedical applications including the targeted delivery of toxic drugs. In the nearer term, HCR has the potential to facilitate the construction of versatile and inexpensive biosensors. Undergraduates have the opportunity to participate fully in this interdisciplinary research through the Caltech Summer Undergraduate Research Fellowship program. Researchers at other universities can freely download source code for the analysis and design software developed in the Pierce Lab. At Pasadena public schools, 62% of students participate in free or reduced-price meal programs and more than 80% of students are underrepresented minorities. For many students, the Jr. Teacher program will provide a rare opportunity to consider the attractions of pursuing a career in science or engineering.

加州理工学院的皮尔斯实验室提出了一项研究计划，该计划结合了理论、计算和实验部分，以推进结构核酸纳米技术领域的发展，开发严格而稳健的方法来编码核酸序列中的任意机械功能。建模和算法开发项目将解决关键的分析和设计挑战。假结生物物理学的研究将有助于为配分函数算法创造基于物理的潜力，并阐明拓扑在“接吻发夹”机制行为中的作用，该机制是在催化燃料输送到自主设备的实验研究中以及：一种有效的分层突变算法，用于使用配分函数信息优化目标二级结构的亲和力和特异性 - 用于识别和设计能源景观的多个特征的方法，包括与自主设备设计相关的亚稳态网络 - 以及制定和优化多-客观设计器件工程的特征问题，其中多条链必须根据存在的链种类的子集有条件地采用不同的结构。智力优点所提出的研究计划旨在开发分析和设计工具，以显着提高严谨性、准确性和科学性的水平。核酸装置设计的自动化。这项工作包括物理建模、算法开发、机制设计和实验验证，其统一目标是能够操纵多种能量景观中的微妙特征，这些能量景观是具有许多条件稳定状态的设备设计的基础。实用的催化燃料输送方法的开发以及随后建造的能够独立行走数百次的强大的自动步行器将代表该领域的突破。同样，HCR 为核酸纳米技术提供了一种新的功能范式，为研究创造了许多有吸引力的途径。更广泛的影响在纳米长度尺度上设计自主设备的能力有一天可能会产生重要的医学应用，包括有毒药物的靶向输送。从近期来看，HCR 有潜力促进多功能且廉价的生物传感器的构建。本科生有机会通过加州理工学院夏季本科生研究奖学金计划充分参与这项跨学科研究。其他大学的研究人员可以免费下载皮尔斯实验室开发的分析和设计软件的源代码。在帕萨迪纳公立学校，62% 的学生参加免费或减价餐计划，超过 80% 的学生是少数族裔。对于许多学生来说，初级教师计划将提供一个难得的机会来考虑从事科学或工程职业的吸引力。