Hosted by the School of Biochemistry
Abstract: Microtubules are dynamic polymers that are remodeled in response to a variety of cellular and environmental cues. However, the fundamental molecular mechanisms underlying microtubule dynamics are not fully understood. During my doctoral studies in cell biology, I investigated the roles of microtubules in regulating the mitochondrial network during cytokinesis. I became fascinated by microtubule dynamics and realized there is still so much to learn. Thus, for my postdoctoral research, I harnessed the power of bottom-up, in vitro reconstitution approaches combining purified proteins with total-internal-reflection fluorescence microscopy to investigate microtubule dynamics regulation. Notably, I discovered that CLASP2 regulates microtubule stability by modulating the transitions between microtubule growth and shrinkage while leaving the growth and shrinkage rates unaffected. This result challenges traditional models of microtubule dynamics that predict direct relationships between the dynamics parameters. Further, we found that CLASP2 synergizes with EB1, a microtubule-tip tracking protein. Increasing complexity, we find that the action of CLASP2 in combination with EB1, MCAK, and XMAP215 results in microtubule treadmilling, a behavior observed in spindle microtubules. These findings underscore the synergistic relationships that arise through the collective effects of groups of proteins acting on microtubules. Finally, I found that SSNA1, is a novel sensor of microtubule lattice damage, placing SSNA1 in the microtubule damage-repair pathway. In my own laboratory, the overarching goal of my future research will be to uncover the molecular mechanisms underlying microtubule dynamics regulation during cellular microtubule network remodeling. I will employ a multidisciplinary approach integrating the expertise gained during my prior training in cell biology, biophysics, and biochemistry, placing me in a unique position to bridge the gap from the molecule to the cell level. Understanding how microtubule dynamics are orchestrated to support dynamic cellular processes is critical to understanding the role of microtubules in health and disease.