BRIGE: Mechanics of DNA Motors for Moving Polarity

这项扩大参与工程研究启动基金（bridge）为了解DNA马达决定其移动极性的机制提供了资金。DNA马达是一种分子机器，它可以移动活细胞中的DNA来完成许多基本任务。尽管它们意义重大，但我们对它们驱动DNA运动的机制的理解是有限的。具体来说，DNA马达是如何在移动DNA链时保持高保真度的特定极性的，这在很大程度上仍然是难以捉摸的，无论是3‘-5’马达从DNA链的3‘端移动到5’端，还是相反的5‘-3’马达。令人惊讶的是，3‘-5’电机和5‘-3’电机的结构是相似的，这进一步挑战了这些电机的机械研究，以解释它们不同的极性。本项目旨在研究3‘-5’和5'-3' DNA马达的力学，以实现以下两个研究目标：(1)确定3‘-5’和5'-3' DNA马达的力转导；(2)确定3‘-5’和5'-3' DNA马达的结构对其变形的影响。对DNA马达的力学研究将使我们更好地理解DNA马达的设计原理，为未来设计具有特定极性的DNA马达提供便利。这项研究的结果将为新的应用打开大门，如电机引导DNA测序，电机传递基因药物，以及用于纳米生物技术应用的电机折叠3D DNA支架。就教育目标而言，该研究将是高度跨学科的，需要多个领域的知识，因此它将促进下一代工程师整合从工程和生物学科中学习的知识。该项目将特别强调通过为少数民族高中生提供研究和演讲机会，扩大代表性不足群体的参与。

This Broadening Participation Research Initiation Grants in Engineering (BRIGE) grant provides funding to understand the mechanism of DNA motors dictating their moving polarity. DNA motors are molecular machines that move DNA in living cells to accomplish numerous essential tasks. Despite their enormous significance, our understanding of their mechanics that drives the motion of DNA is limited. Specifically, it remains largely elusive how a DNA motor maintains specific polarity with high fidelity when moving DNA strands, either from the 3' to the 5' end of a DNA strand for a 3'-5' motor, or the opposite for a 5'-3' motor. Surprisingly, the structures of a 3'-5' motor and a 5'-3' motor are similar, further challenging the mechanical studies of these motors to explain their distinct polarities. This project aims to study the mechanics of both 3'-5' and 5'-3' DNA motors to achieve the following two research goals: (1) Determine the force transduction of 3'-5' and 5'-3' DNA motors, and (2) Determine structural effects on the deformation of 3'-5' and 5'-3' DNA motors. The mechanical studies of DNA motors will enable us to better understand the design principles of DNA motors, facilitating the future design of DNA motors with specified polarity. The results of the study will open doors to new applications such as motor-guided DNA sequencing, motor-delivered gene drugs, and motor-folded 3D DNA scaffolds for nanobiotechnology applications. In terms of education goals, this research will be highly interdisciplinary that requires knowledge in multiple areas, so it will advance the next-generation engineers in integrating knowledge learned from engineering and biological disciplines. This project will specifically emphasize the broadening of participation of underrepresented groups by providing research and lecture opportunities for minority high-school students.