In addition to providing structural support, microtubules form a complex and dynamic intracellular "highway" that delivers molecular cargo from one end of the cell to another -which in the case of neuronal cells can span several feet. Given the continually changing cell physiology, this delivery system undergoes constant remodeling as cargo is transported to different destinations with high temporal and spatial accuracy. Failures in this highly coordinated transport system lead to disease and mutations in genes that encode microtubule dynamics regulators have been implicated in neurodegeneration, cardiovascular disease, cancers and viral infections.
Not surprisingly, tubulin, the building block of the microtubule network is one of the most post-translationally modified proteins in the cell. My laboratory combines biophysical and cell biological approaches to understand the interplay between microtubules and their regulators and how the chemical complexity of microtubules tunes the behavior of motors and microtubule associated proteins. Despite the abundance and complexity of tubulin modifications, their effects on microtubule behavior are still poorly understood. Is the microtubule more than just a structural strut, or a naive roadway for cellular components to transit along? Is there a "tubulin code", written in the rich language of the post-translational modifications of tubulin that, much like a histone code, provides specificity and regulation to cellular dynamics and to the trafficking of motor proteins and their cargo on the cellular highway? How functional diversity is imparted to different microtubules is a central question in cell biology with important implications for human health.