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，计算和实验组件，以推进结构核酸纳米技术领域，开发严格和强大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。对伪结生物物理学的研究将有助于为配分函数算法创建基于物理的潜力，并阐明拓扑结构在实验研究中的"接吻发夹"机制行为中的作用，用于催化燃料输送到自主设备，以及：-实施有效的分层突变算法，用于优化亲和力和特异性， 用于识别和设计能量景观的多个特征的方法，所述能量景观包括 与自主器件设计相关的亚稳态--并阐述和优化表征器件的多目标设计问题 工程，其中多个链必须有条件地采用不同的结构，这取决于链物种的子集是present.Intellectual MeritThe拟议的研究计划，旨在开发分析和设计工具，将大大提高水平的严谨性，准确性和自动化与核酸设备的工程。这项工作包括物理建模、算法开发、机制设计和实验验证，其统一目标是实现对多个能量景观中的细微特征的操纵，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。开发一种实用的催化燃料输送方法和随后建造一种坚固的自主步行者，这种步行者可以在没有辅助的情况下走数百步，这将是该领域的一个突破。同样，HCR为核酸纳米技术提供了一个新的功能范例，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可能有一天会有重要的医疗应用，包括有毒药物的靶向递送。在近期内，HCR有可能促进多功能和廉价的生物传感器的建设。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一跨学科研究。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的膳食计划，超过80%的学生是代表性不足的少数民族。对于许多学生来说，Jr.教师计划将提供一个难得的机会，考虑追求科学或工程事业的吸引力。