The Role of Flightin Phosphorylation in Thick Filament Assembly and Flight Muscle Mechanics in Drosophila

肌肉是动物体内最丰富的组织之一，也是运动力量的主要来源。在细胞水平上，肌肉的一个显著特征是化学上不同的细蛋白丝和粗蛋白丝的有组织的交错，这将粗蛋白丝中分子马达的纳米运动转化为动物运动。粗丝已知由运动蛋白肌凝蛋白组成，但肌凝蛋白分子组装成均匀长度的粗丝的方式仍然未知，很可能涉及额外的调节蛋白。本项目研究了调节蛋白flightin在果蝇飞行肌模型系统（Drosophila melanogaster）肌肉粗丝组织和功能中的潜在作用。昆虫的飞行肌肉被认为是动物王国中最强大的肌肉之一。生物化学和基因实验的结合被用来定义飞行蛋白的功能特性，它产生振荡功，很像脊椎动物的心肌。该研究还探讨了飞行对飞行肌肉力学性能的影响机制。该项目将经典遗传学方法与分子生物学、生物化学、细胞结构以及最先进的分子成像和肌肉生理学技术相结合。这种多学科的方法将导致对飞行蛋白功能角色的连贯、综合的看法，并为肌肉发育过程中粗纤维组装的机制以及振荡肌肉产生高功率输出的机制提供有价值的见解。这项研究在果蝇和肌肉研究社区的教育和生物试剂的产生方面都有相当广泛的影响。以前NSF对该实验室的资助有助于培养本科生和研究生，包括来自代表性不足群体的学生的参与，目前的项目延续了这一传统。

Muscle is one of the most abundant tissues in the animal body and the primary producer of force for movement. A remarkable feature of muscle, at the cellular level, is the organized interdigitation of chemically distinct thin and thick protein filaments that translate the nanometer movements of molecular motors in the thick filament into animal locomotion. Thick filaments are known to be composed of the motor protein myosin, but the manner by which myosin molecules assemble into thick filaments of uniform length is still unknown and most likely involves additional regulatory proteins. This project studies potential roles for the regulatory protein flightin in the organization and function of muscle thick filaments in a model system, the flight muscle of the fruit fly Drosophila melanogaster. Insect flight muscle is known to be one of the most powerful muscles in the animal kingdom. A combination of biochemical and genetic experiments are used to define the functional properties of flightin, which generates oscillatory work, much like vertebrate cardiac muscle. The research also investigates the mechanism by which flightin contributes to the mechanical properties of flight muscle. This project combines classical genetics approaches with molecular biology, biochemistry, cell structure, and state-of-the-art molecular imaging and muscle physiology techniques. This multidisciplinary approach will result in a coherent, integrated view of the functional roles of flightin and provide valuable insight into the mechanism of thick filament assembly during muscle development, and the mechanism by which oscillatory muscles produce high power output.This research has considerable broader impact both in both education and in the generation of biological reagents for the Drosophila and muscle research communities. Previous NSF funding to this lab has been instrumental in training undergraduate and graduate students, including the participation of students from underrepresented groups, and the current project continues this tradition.