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

非技术性DNA是一种众所周知的具有双螺旋结构的生物分子。最近，DNA被折叠成各种不同的2D和3D形状，超越了双螺旋结构，产生了用于工程或制药目的的有趣材料。然而，一旦组装起来，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，创造出可以在提示下改变属性的材料。例如，在飞行中折叠DNA将允许材料折叠起来在体内运输，然后展开以在特定时间或地点激活，从而改进药物输送和生物技术。该提案的更广泛目标是培养一批从事科学职业的多样化学生。要做到这一点，该提案首先呼吁发展跨学科的、“即插即用”的课堂实验室。这些实验可以“插入”到多个部门的不同课程中，并在一天内“进行”。以这种方式进行的跨学科培训已被证明可以提高在职解决问题的能力。其次，该提案呼吁通过与女性科学协会(AWIS)合作，创建媒体和指导网络，为科学职业招募、留住和培训学生，从而增加多样性。需要增加科学的多样性，以满足对精通技术的劳动力的需求。技术DNA是一种重要的生物材料，可以很容易地自组装成各种2D和3D超分子结构。然而，一旦组装完成，这些结构通常是静态的。设计DNA组件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。这项职业奖提出了一种新的仿生方法，利用细胞中通常折叠、塑造和环化DNA的重塑蛋白质来创建可重新配置的DNA组件。具体地说，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的情况下在体外组装时的途径和潜在的能量学。了解这种复杂的重组将是生产具有精细调控、结构或机械控制的DNA纳米材料的重要开创性步骤。该提案的更广泛影响是增加本科生进入科学、技术、工程和数学(STEM)的跨学科培训和多样性。为了增加跨学科培训，研究型实验室的培训模块将发展成即插即用的软物质教学实验室，可以在多个系的广泛课程中进行即插即用，在一天内即可完成。此外，该提案还呼吁与高级实验室物理协会合作，就如何实施实验室对教师进行培训。跨学科培训已被证明可以提高创造力和冒险能力，这对解决工作中的复杂问题很重要。为了增加多样性，该提案呼吁与女性科学协会(AWIS)合作，创建由不同科学家组成的招聘媒体，建立一个当地同行指导网络来留住学生，并制作一系列职业手册，为学生进入STEM职业生涯做准备。随着美国人口变得更加多样化，对精通技术的劳动力的需求增加，增加STEM的多样性是NSF的优先事项。

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.