Speaker
Description
Microtubules are protein polymers comprised of tubulin, which are polarized and facilitate intracellular transport. A stable microtubule structure is important to ensure the long-term survival of neurons. However, microtubules also need to be dynamic and reorganize in response to injury events, which results in an increase in microtubule dynamics. How this complex balance is achieved on different scales remains an open question. Using experimental data and a stochastic mathematical model that limits microtubule growth, we seek to understand how nucleation, or new microtubules, can impact microtubule dynamics in dendrites of fruit fly neurons. We develop a partial differential equation (PDE) model that describes microtubule growth and nucleation dynamics to gain analytical insight to our stochastic model, and we compare analytical results to results from the complex stochastic model. Insights from these models can then be used to understand how microtubules can organize into polarized structures in neurons, where several mechanisms have been hypothesized to regulate microtubule polarity organization. Guided by experimental results, we implement our stochastic model with spatial polarity mechanisms to understand the efficacy of proposed biological mechanisms at establishing and maintaining the microtubule polarity observed in healthy neurons. Finally, we utilize our framework to explore mechanisms important in injury, where microtubule polarity is known to reverse.
