Figure 2: The Drosophila Larval musculature. -- A) Lateral view of a Drosophila 3rd instar larva that carries a muscle specific red fluorescent transgene that highlights all muscles. B) Close up of one larval muscle showing the contractile units (sarcomeres- red) and the arrangement of nuclei (white) of one muscle.
Skeletal muscles come in a variety of shapes and sizes, each tuned to a particular function — from the muscles that allow a person to run to those that focus the eye. Individual muscles also have different susceptibilities to diseases like muscular dystrophy, muscle myopathies, and rhabdomyosarcoma.
Therapies that repair muscle wasting due to aging or disease require the ability to generate specific muscle types of a particular size and shape. Therefore, identifying the mechanisms of how muscles differentiate, as well as how they grow and respond to disease, is critical. My lab focuses on the following questions:
- How are muscle cells specified?
- How are they maintained during growth and use?
- How do they respond and change during disease?
To assay muscle function, we use a larval crawling assay shown in this video clip. Larva on the right is a control and moves effortlessly towards an attractive odor. Larva on left has mispositioned nuclei in muscle. This larva cannot move efficiently.
Our primary model system is the Drosophila musculature, in which we employ genetics, molecular and cell biological approaches, bioinformatics, in vivo time-lapse imaging, and biochemistry to identify and characterize genes required for muscle formation, use, and maintenance. (See Figures 1, 2) We also use mammalian muscle models to confirm and extend the paradigms that we develop in Drosophila.
Currently, we study two significant areas of muscle biology:
Fundamental mechanisms governing muscle formation and maintenance. These projects include investigation of muscle identity, muscle cell size, and muscle subcellular organization.
Mechanisms underlying muscle disease. These projects investigate disease progression and novel therapeutics for two muscle diseases, rhabdomyosarcoma and nemaline myopathy. (See Larval Crawling Assay video)