CAREER: Elucidating acentrosomal microtubule organization by integrating cell biology, single molecule imaging and computational modeling

Washington University, Saint Louis MO

Investigators

Abstract

Control of cell shape is a fundamental property of life, essential to the form and function of all organisms. Cell shape is governed primarily by an internal scaffolding structure called the cytoskeleton. Unlike human-made scaffolding structures, the cytoskeleton is highly dynamic and is able to change its configuration in response to developmental and environmental signals, allowing cells to adapt to changing conditions. This project uses the cortical microtubule cytoskeleton of plants as a model to understand how microtubule polymers form highly ordered arrays in the absence of a centralized organizing mechanism. By integrating approaches scaling from single molecules to whole cells, this research will reveal principles by which biochemical activities at the molecular scale result in complex microtubule arrays at the cellular scale, principles expected to be applicable to other such arrays. Since the plant cortical microtubule array directs cell wall assembly, this work might also lead to new strategies to engineer plant biomass for improved food and cellulosic biofuel production. The work from this project will be integrated into education and outreach through inquiry-based activities at multiple levels across the K-20 education spectrum. Specifically, the PI will incorporate this work into a course for Architecture students to inspire new human-made structures based on cellular design principles and a new professional development workshop on Biological Self-Organization to provide high-school teachers with a mathematical biology resource to help them meet the Next Generation Science Standards. He will also integrate work from this project into a problem-based Teen Science Café program, which attracts between 1,000-1,500 students from grades 6-12 annually and is a great opportunity to teach the scientific inquiry process and about dynamic cellular events. The PI will study how noncentrosomal microtubules form highly ordered arrays without the benefit of an organizing center. This problem is fundamentally important because noncentrosomal microtubule arrays are vital for the structure and function of evolutionarily diverse organisms such as fission yeast, humans and plants. To elucidate the underlying mechanisms, the PI will use the cortical microtubule cytoskeleton of Arabidopsis thaliana plants as an experimentally tractable model system. The PI hypothesizes that the net balance of multiple microtubule-associated proteins dynamically controls array structure by regulating the trajectory, length and dynamics of cortical microtubules. To test this hypothesis, a combination of live imaging, in vitro experiments at single molecule resolution and computational modeling will be used to: 1) determine the function of EB1 and associated proteins in regulating the behavior of cortical microtubules, 2) investigate the role of microtubule bundling in array organization, 3) determine how distinct molecular activities interact in space and time to dynamically pattern cortical microtubules, and 4) elucidate the mechanisms that define and change cortical microtubule array orientation in response to developmental and environmental signals. Together, this research will advance our understanding of how distinct cortical microtubule arrays are built to create different cell shapes and how arrays are remodeled in response to signals to modify plant growth. The work from this project will be integrated into multiple education and outreach activities to introduce new biological concepts and techniques into classrooms and to get students interested in pursuing a STEM career. The PI will incorporate this work into a course for Architecture students to inspire new architectural designs based on principles underlying cellular architecture. The PI will also lead a professional development workshop on Biological Self-Organization for high-school teachers, which will combine hands-on activities and computer modeling to provide a mathematical biology resource to take back to classroom. He will also integrate work from this project into a problem-based Teen Science Café program for students from grades 6-12 to teach the scientific inquiry process and about dynamic cellular events.