Probing the Mechanics of the Axoneme in Genetically-Modified Flagella

该奖项的研究目标是测量产生推进运动的纤毛和鞭毛的机械性能和主动过程。纤毛和鞭毛是微小的亚细胞结构（直径约200纳米，长5-30微米），它们有规律地跳动以推动细胞或移动液体。纤毛排列在人体呼吸系统的气道上，并协调跳动以消除细菌和颗粒。在这个项目中，将测量海藻鞭毛的弹性刚度和产生力的能力，它们的结构和行为与人类的纤毛非常相似。机械性能将在具有特定基因突变的鞭毛中进行测试，在不同的实验条件下，以了解潜在的结构特征如何产生有效推进所需的协调振荡。力学和遗传学的新结合是唯一适合在这个问题上取得进展的方法。如果成功，这些研究将推进我们对纤毛和鞭毛的科学理解，并为这些系统如何在受伤或疾病中失败提供见解。这种更好的理解可能会带来新的诊断和治疗方法，或者从生物振荡器中获取能量的方法。更一般地说，这些研究将澄清协调机制，使许多独立的微观振荡器一起工作，产生宏观运动。该项目将通过华盛顿大学（WU，一所研究型私立大学）和中央俄克拉荷马大学（UCO，一所专注于本科教育的公共机构）之间的合作伙伴关系产生广泛的影响。通过这种伙伴关系，来自两所大学的本科生将参与研究，从而增加了对不同人群的这种经验的可用性。该奖项还将支持由高中生和大学生设计大型纤毛和鞭毛物理模型的教育项目。这些模型将阐明纤毛和鞭毛的行为，同时为机电设计和控制提供实践经验。

The research objective of this award is to measure the mechanical properties and active processes that produce propulsive motion in cilia and flagella. Cilia and flagella are tiny subcellular structures (about 200 nanometers in diameter and 5-30 micrometers long) that beat regularly to propel cells or to move fluid. Cilia line the airways of the human respiratory system and beat in coordination to eliminate bacteria and particles. In this project, elastic stiffness and ability to produce force will be measured in algae flagella, which have structure and behavior very similar to human cilia. Mechanical properties will be tested in flagella with specific genetic mutations, under varying experimental conditions, to learn how the underlying structural features produce the coordinated oscillations required for effective propulsion. The novel combination of mechanics and genetics is uniquely suited to make progress on this problem. If successful, these studies will advance our scientific understanding of cilia and flagella, and provide insight into how these systems fail in injury or disease. This improved understanding could lead to new methods for diagnosis and therapy, or ways to harvest energy from biological oscillators. More generally, these studies will clarify the coordination mechanisms which allow many independent microscopic oscillators to work together to produce macroscopic motion. The project will achieve broad impact through a partnership between Washington University (WU; a research-intensive private university) and the University of Central Oklahoma (UCO; a public institution focused on undergraduate education). Through this partnership, undergraduate students from both institutions will participate in research, enhancing the availability of such experiences to a diverse population. This award will also support educational projects in which high school and undergraduate students design large-scale, physical models of cilia and flagella. These models will illuminate the behavior of cilia and flagella while providing practical experience in electromechanical design and control.