CAREER: Investigating reconfigurable DNA self-assembly at the molecular scale

职业：在分子尺度上研究可重构 DNA 自组装

• 批准号: 1653501
• 负责人: Ashley Carter
• 金额: $ 50万
• 依托单位: Amherst College
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-01-15 至 2022-12-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1653501&HistoricalAwards=false
• 关键词: CAREER; Investigating; reconfigurable; DNA; self

Non-TechnicalDNA is a well-known biomolecule with a double helix structure. Recently, DNA has been folded into a wide variety of 2D and 3D shapes beyond the double helix, producing interesting materials for engineering or pharmaceutical purposes. However, once assembled, the folded DNA shapes are fixed. This CAREER award investigates how to fold DNA on the fly, creating materials that could change properties on cue. For example, folding DNA on the fly would allow for materials to be folded up for transport through the body and later unfolded for activation at a particular time or place, improving drug delivery and biotechnology. The broader goals of the proposal are to train a diverse set of students for careers in science. To do this, the proposal first calls for developing interdisciplinary, "plug and play" classroom laboratories. These labs can be "plugged" into different courses across many departments and "played" on a single day. Interdisciplinary training in this way has been shown to increase on-the-job, problem-solving abilities. Second, the proposal calls for increasing diversity by partnering with the Association of Women in Science (AWIS) to create media and mentoring networks that recruit, retain, and train students for science careers. Increasing diversity in science is needed to meet the demands for a technologically savvy workforce. TechnicalDNA is an important biomaterial that easily self-assembles into a wide variety of 2D and 3D supramolecular structures. However, once assembled, these structures are often static. Engineering DNA assemblies to respond to proteins would allow for dynamic changes in regulatory behavior, structure, or mechanical properties. This CAREER award proposes a novel biomimetic approach to create reconfigurable DNA assemblies using the remodeling proteins in the cell that typically fold, shape, and loop the DNA. Specifically, experiments will-for the first time- directly measure the pathway and underlying energetics of single DNA molecules as they assemble in vitro in the presence of a remodeling protein, protamine. Understanding this complex reconfiguration will be an important pioneering step in producing DNA-based nanomaterials with exquisite regulatory, structural, or mechanical control.The broader impact of the proposal is to increase the interdisciplinary training and diversity of undergraduate students entering science, technology, engineering, and math (STEM). To increase interdisciplinary training, research laboratory training modules will be developed into "plug and play" soft matter teaching laboratories that can be "plugged" into a broad range of courses in multiple departments and "played" on a single day. In addition, the proposal calls for partnering with the Advanced Laboratory Physics Association to train instructors on how to implement the laboratories. Interdisciplinary training has been shown to increase creativity and the ability to take risks, important for on-the-job, complex problem solving. To increase diversity, the proposal calls for partnering with the Association of Women in Science (AWIS) to create recruitment media with diverse scientists, a local peer mentoring network to retain students, and a series of career brochures to prepare students for STEM careers. Increasing diversity in STEM is a priority for the NSF as the US population becomes more diverse and the demands for a technologically savvy workforce are increased.

非技术DNA是一种众所周知的具有双螺旋结构的生物分子。最近，DNA已经被折叠成各种各样的2D和3D形状，超出了双螺旋，产生了用于工程或制药目的的有趣材料。然而，一旦组装，折叠的DNA形状就固定了。这个职业奖研究如何在飞行中折叠DNA，创造可以改变性质的材料。例如，在飞行中折叠DNA将允许材料被折叠以通过身体运输，然后在特定的时间或地点展开以激活，从而改善药物递送和生物技术。该提案的更广泛目标是培养一批多样化的学生从事科学事业。为此，该提案首先呼吁开发跨学科的“即插即用”课堂实验室。这些实验室可以“插入”到许多部门的不同课程中，并在一天内“播放”。以这种方式进行跨学科培训已被证明可以提高在职解决问题的能力。其次，该提案呼吁通过与科学界女性协会（AWIS）合作，建立媒体和指导网络，招募，保留和培训学生从事科学职业，从而增加多样性。为了满足对精通技术的劳动力的需求，需要增加科学的多样性。TechnicalDNA是一种重要的生物材料，可以很容易地自组装成各种各样的2D和3D超分子结构。然而，一旦组装，这些结构通常是静态的。设计DNA组装以响应蛋白质将允许调节行为、结构或机械特性的动态变化。这个CAREER奖提出了一种新的仿生方法，使用细胞中的重塑蛋白质来创建可重构的DNA组装体，这些蛋白质通常会折叠，塑造和循环DNA。具体来说，实验将首次直接测量单个DNA分子在重塑蛋白鱼精蛋白存在下体外组装时的途径和潜在能量学。了解这种复杂的重新配置将是生产具有精细监管，结构或机械控制的基于DNA的纳米材料的重要开拓性一步。该提案的更广泛影响是增加跨学科培训和本科生进入科学，技术，工程和数学（STEM）的多样性。为了增加跨学科培训，研究实验室培训模块将发展成为“即插即用”的软物质教学实验室，可以“插入”到多个部门的广泛课程中，并在一天内“播放”。此外，该提案呼吁与高级实验室物理协会合作，培训教师如何实施实验室。跨学科培训已被证明可以提高创造力和承担风险的能力，这对在职解决复杂问题很重要。为了增加多样性，该提案呼吁与科学界女性协会（AWIS）合作，创建具有不同科学家的招聘媒体，建立本地同行指导网络以留住学生，并制作一系列职业手册以帮助学生为STEM职业做好准备。增加STEM的多样性是NSF的优先事项，因为美国人口变得更加多样化，对精通技术的劳动力的需求也在增加。

项目成果

Optical methods for measuring DNA folding

测量 DNA 折叠的光学方法

• DOI: 10.1142/s0217984917300010
• 发表时间: 2017
• 期刊: Modern Physics Letters B
• 影响因子: 1.9
• 作者: Smith, Adam D.;Ukogu, Obinna A.;Devenica, Luka M.;White, Elizabeth D.;Carter, Ashley R.
• 通讯作者: Carter, Ashley R.

On building a research lab, not starting one

关于建立一个研究实验室，而不是开始一个

• DOI: 10.1119/1.5100108
• 发表时间: 2019
• 期刊: American Journal of Physics
• 影响因子: 0.9
• 作者: Carter, Ashley R.

One Hundred Years Later, Introductory Labs Are Poised for Change

一百年后，入门实验室已做好变革的准备

• DOI: 10.1119/10.0003460
• 发表时间: 2021
• 期刊: The Physics Teacher
• 作者: Carter, Ashley R.

Protamine loops DNA in multiple steps

• DOI: 10.1093/nar/gkaa365
• 发表时间: 2020-05
• 期刊: Nucleic Acids Research
• 影响因子: 14.9
• 作者: Obinna Ukogu;A. Smith;L. Devenica;Hilary Bediako;Ryan B. McMillan;Yuxing E. Ma;Ashwin Balaji;R. D. Schwab;Shahzad Anwar;M. Dasgupta;Ashley R. Carter

Perspectives on How 1.5 Years of the COVID-19 Pandemic Have Impacted Biophysicists at Primarily Undergraduate Institutions

1.5 年的 COVID-19 大流行如何影响本科院校的生物物理学家的观点

• DOI: 10.35459/tbp.2021.000187
• 发表时间: 2022
• 期刊: The Biophysicist
• 作者: Soto, Patricia;Carter, Ashley R.;Deligkaris, Christos;Gül, Duygucan;Hamadani, Kambiz M.;Knight, Jefferson;Matulis, Daumantas;Ozturk, Tugba N.;Rivera-Colón, Yadilette;Yates, Elizabeth A.
• 通讯作者: Yates, Elizabeth A.