Department of Cell and Developmental Biology
465 21st Avenue South
Nashville, TN 37240
2016 Searle Scholar
Dynamic Architecture of the Microtubule Cytoskeleton
A look inside of every living cell reveals a world of dynamic intracellular structures. A number of these structures are built of microtubule polymers, known for their essential function in many fundamental cellular processes. For a cell to divide, microtubules form the mitotic spindle, an intricate molecular machine that captures chromosomes and pulls them apart. For a sperm to swim, microtubules slide against each other in a highly coordinated manner within a precisely organized bundle to generate the bending motion of the sperm tail. For a neuron to grow and survive, microtubules build a complex roadmap for directed long-range transport of intracellular cargos. How can these polymers perform such a wide variety of roles? The answer lies in the unique ability of individual microtubules to dynamically respond to cellular cues in space and time.
Our research aims to discover the fundamental biophysical principles underlying the dynamic architecture of the microtubule cytoskeleton. What are the molecular rules that govern whether an individual microtubule grows or shrinks at any given moment in time? What are the mechanisms used by the microtubule-associated proteins that regulate microtubule behavior? How does this complex network of microtubule regulators collectively orchestrate dynamic remodeling of the microtubule cytoskeleton in vastly diverse cellular contexts? To address these questions my lab takes a united interdisciplinary approach. Inspired by conceptual models developed using cell biological tools, we employ biochemical in vitro reconstitution with purified protein components, single-molecule total-internal-reflection-fluorescence (TIRF) imaging, and microfluidics techniques to obtain a quantitative description of dynamic microtubule behavior. This quantitative characterization in turn leads to the development of predictive, testable mathematical models that have the power to elucidate the molecular mechanisms of active microtubule organization.
The dynamic self-organization of the microtubule system serves as the perfect example of a complex behavior arising from the collective effects of groups of proteins. Cells are rich with such examples of emergent behaviors that we are only just beginning to uncover. These cellular phenomena call for new multidisciplinary approaches. Uniting the tools of biology and physics, our work will ultimately pave the way to the fundamental understanding of how cells engineer large-scale, dynamic structures essential for life.
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