α/β-tubulin heterodimers form dynamic polymers, microtubules, that are central to cellular processes, such as cell division, cell migration, and organelle transportation. The α- and β-tubulin gene families (i.e. isotypes) expand substantially in metazoans. The human genome encodes at least nine α- and ten β-tubulin isotypes that have the protein expression profiles varying with cell types and developmental stages. Single point mutations in specific tubulin isotypes have been associated with human diseases. The discovery of disease-related mutations suggests that, even with the high degree of identity on the primary sequence basis, tubulin isotypes do not complement each other’s function in metazoans. However, the molecular mechanism by which tubulin isotypes regulate the organization and function of microtubules remains poorly understood.
Featuring the field-leading technology to generate isotypically pure recombinant human tubulin, Dr. Ti’s laboratory employs combinatorial approaches of biochemistry, biophysics, chemical biology, and structural biology to dissect the factors that are associated with the biological function of diverse human tubulin isotypes.