Mechanical architecture of chromosome segregation
Life is a chemical as well as mechanical process. At the nanometer scale, mechanoenzymes interconvert force and chemical potential. At the micrometer scale, cells spatially organize their constituents, change shape and move. At the millimeter scale, organisms develop and also move. While we know a lot about the chemistry of life processes, we know much less about their mechanics. How are mechanical and chemical processes integrated over molecular, cellular and tissue length scales?
Our lab aims to understand how cells coordinate mechanical and chemical activities to equally distribute their genetic material when they divide. During cell division, each daughter cell must inherit exactly one copy of each chromosome. How do cells generate, detect and respond to mechanical force to accurately segregate their chromosomes? Errors in chromosome segregation can lead to birth defects and disease. While we have a nearly complete list of molecules essential to cell division, we know very little about the underlying mechanical interactions and principles. New approaches are needed. We are using new biophysical and molecular tools to probe the mechanical architecture of the cell’s chromosome segregation machines.
Two macromolecular machines coordinate chromosome segregation: the spindle moves chromosomes through its growing and shrinking microtubules, and the kinetochore anchors chromosomes to spindle microtubules and regulates their segregation. How are these two machines designed to accurately and robustly divide chromosomes? How do their nm-scale constituents work together to generate µm-scale movements? To probe the mechanical architecture of these machines, we combine mechanical perturbations and readouts with high resolution imaging and molecular perturbations. Together, our work will build fundamental knowledge in how mechanical and chemical processes are integrated over cellular length scales, and in life processes that, if perturbed, cause disease.