The Gardner Laboratory uses a combination experimental and computational approach to dissect molecular mechanisms for how microtubule lengths are regulated inside of cells. We use biophysical computational modeling to better integrate and understand our experimental observations, make new experimental predictions, and to test whether our proposed cellular mechanisms are physically reasonable. Overall, we are a cellular biophysics laboratory that combines cell biology tools with biophysical methods to shed new light on the regulation of microtubule dynamics during mitosis. Achieving the goals described in this application will allow us to expand the sources of tubulin that can be used for imaging of microtubule dynamics, thus establishing stronger connections between cellular and organismal phenotypes, especially through the use of targeted mutagenesis. Our first project will involve the pathogenic yeast Candida albicans. Thus, we will advance our understanding of (a) how C. albicans microtubule dynamics compare to mammalian microtubule dynamics, (b) how a range of current microtubule-targeting drugs differentially alter microtubule dynamics in C. albicans relative to mammalian tubulin, and (c) how changes in microtubule dynamics parameters lead to the disruption of cell division in the pathogenic yeast C. albicans, as compared to in human cells. Further, we expect that computational modeling and ultrastructural analysis of C. albicans tubulin will allow us to connect molecular-level and cellular-level drug phenotypes and outcomes.