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

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二维和三维形状，而不是双螺旋结构，为工程或制药目的生产有趣的材料。然而，一旦组装，折叠的DNA形状是固定的。这个职业奖研究的是如何在飞行中折叠DNA，创造出可以随时改变属性的材料。例如，在苍蝇上折叠DNA可以让材料折叠起来通过身体运输，然后在特定的时间或地点展开激活，从而改善药物输送和生物技术。该提案更广泛的目标是为科学事业培养多样化的学生。为此，该提案首先要求发展跨学科的“即插即用”课堂实验室。这些实验可以“插入”到许多系的不同课程中，并在一天内“玩”。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。第二，该提案呼吁通过与妇女科学协会（AWIS）合作来增加多样性，创建媒体和指导网络，为科学事业招募、留住和培训学生。为了满足对精通技术的劳动力的需求，需要增加科学领域的多样性。技术dna是一种重要的生物材料，容易自组装成各种各样的二维和三维超分子结构。然而，一旦组装起来，这些结构往往是静态的。工程DNA组装响应蛋白质将允许动态变化的调节行为，结构，或机械性能。该职业奖提出了一种新颖的仿生方法，利用细胞中的重塑蛋白来创建可重构的DNA组件，这些蛋白质通常折叠、塑造和环化DNA。具体来说，实验将首次直接测量单个DNA分子在体外重组蛋白（鱼精蛋白）存在下组装时的途径和潜在能量。了解这种复杂的重新配置将是生产具有精细调节，结构或机械控制的dna基纳米材料的重要开创性步骤。该提案的更广泛影响是增加进入科学、技术、工程和数学（STEM）专业的本科生的跨学科培训和多样性。为加强跨学科训练，研究实验室训练模块将发展为“即插即用”的软物质教学实验室，可以“插”进多个院系的广泛课程，一天“玩”一次。此外，该提案呼吁与高级实验室物理协会合作，培训教师如何实施这些实验室。跨学科培训已被证明可以提高创造力和承担风险的能力，这对在职和解决复杂问题很重要。为了增加多样性，该提案呼吁与科学妇女协会（AWIS）合作，创建有不同科学家的招聘媒体，建立一个当地的同伴指导网络来留住学生，以及一系列的职业手册，让学生为STEM职业做好准备。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的多样性是美国国家科学基金会的优先事项。

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.