Understanding the physiological and therapeutic significance of protein isoform switching in muscles
The structural proteins undergo alternative splicing to give multiple muscle tissue-specific isoforms. The expression patterns of these isoforms are regulated both spatially and temporally. Any defect in this regulation leads to abnormal muscle development, resulting in myopathic conditions. The Indirect Flight Muscles (IFM) of Drosophila melanogaster serve as an excellent model system for studying muscle development and disease, due to the high levels of homology with vertebrate structural proteins. We are interested in understanding the regulation of isoform switching in muscles during development as well as in response to a diseased condition.
Understanding IFM (indirect flight muscle) development and maintenance
Muscles perform a myriad of functions in the body, from maintaining posture to aiding various physiological functions. Efficient execution of these functions is possible only when a particular muscle develops normally at a specific site, finds the attachments to adhere to, grows to achieve the appropriate mass required for activity, maintains this mass, acquires an array of sarcomeres, and is fed by proper neuronal cues. This complete process of myogenesis involves a complex series of sequential molecular and cellular events, which are regulated spatially and temporally, to form a characteristic pattern of functional muscles. We are trying to understand temporal regulation of muscle development and maintenance of its structural integrity using Drosophila IFM as a model system.
Dissecting the mechanism of actin isoform switching and modeling nemaline myopathy in Zebrafish
Zebrafish is emerging as a popular model organism to study and understand various biological processes. We are currently exploring the potential of this organism to study congenital myopathies. The effects of these diseases can range from minor to life-threatening, depending on severity. As the pathophysiology of congenital myopathies at the molecular level is poorly understood, we are looking at zebrafish for answers. We are studying isoform switching and its regulation, which is an important compensatory (rescue) phenomenon in myopathies. We are also looking into possible therapeutic measures.
Screening of muscles specific enhancer trap GAL4 strains
Tissue-specific enhancer trap GAL4 strains are indispensable for understanding the molecular mechanisms underlying differentiation of cellular lineages and proper functioning of tissues. Numerous enhancer trap GAL4 insertions with differential expression patterns have been isolated from a screen in our lab. A few strains that show spatio-temporal expression in different subsets of Drosophila thoracic muscles are being characterized.