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，也是运动力的主要产生者。在细胞水平上，肌肉的一个显着特征是化学上不同的薄和厚蛋白质细丝的有组织的交错，这些细丝将粗细丝中分子马达的纳米运动转化为动物运动。已知粗丝由马达蛋白肌球蛋白组成，但肌球蛋白分子组装成均匀长度的粗丝的方式仍然未知，并且很可能涉及额外的调节蛋白。 该项目研究了调节蛋白flightin在模型系统中肌肉粗丝的组织和功能中的潜在作用，果蝇果蝇的飞行肌肉。昆虫的飞行肌肉被认为是动物王国中最强大的肌肉之一。 生物化学和遗传学实验的结合被用来定义flightin的功能特性，它产生振荡工作，很像脊椎动物的心肌。 本研究还探讨了flightin对飞行肌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一个连贯的，综合的观点flightin的功能作用，并提供有价值的深入了解肌肉发育过程中的粗丝组装的机制，以及振荡肌肉产生高功率output.This研究的机制有相当广泛的影响，无论是在教育和生物试剂的果蝇和肌肉研究社区的一代。以前的NSF资助这个实验室一直在培训本科生和研究生，包括来自代表性不足的群体的学生的参与，和目前的项目继续这一传统。

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.