Dr. Minhaj Sirajuddin
STRUCTURE AND FUNCTION OF CYTOSKELETAL ASSEMBLIES
Cytoskeletal assemblies such as actin and microtubules provide the framework for maintaining cell integrity and powers biological motions. Few examples of biological motions include; heart and muscle contraction, sperm motility and intracellular transport of cargos in a meter long neurons. Due to their important functions in eukaryotic cell physiology, mutations in cytoskeletal components have been linked to a variety of human diseases, such as cardiomyopathies, muscular dystrophies and neurodegenerative diseases.
My research interests include understanding the function of cytoskeletal assemblies using structural, biochemical and biophysical approaches. As a part of cardiomyopathy team, my research will focus on bridging the knowledge gap between clinical findings and molecular mechanism underlying cardiomyopathy disease causing mutations. Most of these mutations are located in proteins that are highly enriched in the heart and are important sarcomere components, the basic unit of the cardiomyocyte responsible for generating contractile forces during the heartbeat. However, understanding how single point mutations contribute to the progression of cardiomyopathies remains a challenge. This is largely due to a lack of molecular understanding of how sarcomere proteins coordinate during muscle contraction. In order to address this, our lab will use purified recombinant sarcomere components, which will enable us to measure the collective biophysical properties of core sarcomere proteins and compare with disease mutations. Furthermore, the structural work will involve determining high-resolution structures of uncharacterized sarcomere proteins. These approaches will enable us to tackle longstanding conundrums in the muscle field and motor biophysics, and has the potential towards developing therapeutic intervention for cardiomyopathy diseases.
My other research interests include understanding the function of microtubule and associated proteins. This work will majorly benefit from the recombinant tubulin expression developed during my postdoctoral work. Using this method, our lab will purify microtubules engineered with a particular post-translational modification and study the effects of microtubule track modification on intracellular cargo transport.