Co - Mentor
Regulation of microtubule-dependent transport by the Tubulin Code
Microtubules are cytoskeletal polymers that are vital for a wide range of cellular functions. They serve as tracks for microtubule-based motors (kinesins and dyneins), form the mitotic spindle for proper cell division, and determine the architecture of specialized cellular structures such as cilia and flagella. The building block of microtubules – a heterodimer of α/β-tubulin – is surprisingly diverse in most organisms, owing to the existence of many tubulin isotypes. The physicochemical and dynamic properties of microtubules are also modulated through a panoply of posttranslational modifications (PTMs). The full impact of tubulin isotype diversity and PTMs, collectively referred to as the “Tubulin Code”, on microtubule function in cells is not well understood. The Cianfrocco and Verhey labs are interested in understanding how tubulin diversity regulates intracellular trafficking driven by kinesin and dynein motors. This project seeks to define the tubulin diversity in iPSC-derived neurons and determine how specific isotypes and PTMs regulate kinesin and dynein activity and transport events. The goal is a multi-scale understanding of the Tubulin Code, from its influence on individual motors (reconstitution of motor/cargo complexes in vitro and structural analysis) to the regulation of cargo transport at the cellular scale (live-cell imaging and cryo-electron tomography).