View Program - 63rd Annual Drosophila Research Conference

Cachexia is a wasting syndrome common in late-stage cancer patients, whose symptoms include loss of body fat, weight loss, and muscle weakness/deterioration. To study the cachexic effects on muscles, our lab utilizes a Drosophila melanogaster tumor model which displays the syndrome’s major symptoms. These tumor larvae fail to pupate and display observable physical wasting and symptoms of muscle loss over the period of 8-12 days AEL. In my project, I am distinguishing how the muscle sarcomere structure is changing due to cachexia. I observe a progressive loss of larval skeletal muscle strength was detailed over a five-day span (day 8-12 in development). I determined that there is a progressive loss of the larval skeletal muscle integrity, with late day 12 larvae having many broken muscle fibers. At a subcellular level, loss of sarcomere structure is increasingly common over the progression of the disease. Using immunohistochemistry, I observed that larval skeletal muscle fibers displayed major defects in actin, alpha-actinin, and myosin heavy chain localization towards the later stages of the disease, with fewer disruptions on day 8 or 10. I also observed that of these three molecules, myosin heavy chain shows the earliest and most pervasive phenotypes. From this, it is prophesied that this structural change in the sarcomere protein structure is related to the cause of the breakdown in the larval skeletal muscles. These results suggest that myosin heavy chain mislocalization is an early event in the loss of muscle function and integrity observed in these larvae, and our future studies will investigate if this is due to decreased protein production or increased turnover.

Understanding the Progressive Loss of Larval Muscle Fibers in Cachexia Tumor Model System with Focus on Myosin