A computational model of bipolar mitotic spindle assembly and stability in fission yeast
Mitotic spindles use an elegant bipolar architecture to segregate duplicated chromosomes with high fidelity. Bipolar spindles form from a monopolar initial condition in a fundamental construction problem. Microtubules, motors, and crosslinkers are important for bipolarity, but the mechanisms necessary and sufficient for spindle assembly remain unknown. Here we describe a physical model that exhibits de novo bipolar spindle formation. We began with previously published data on fission-yeast spindle-pole-body size and microtubule number, kinesin-5 motors, kinesin-14 motors, and passive crosslinkers.
Our model results agree quantitatively with our experiments in fission yeast, thereby establishing a minimal system with which to interrogate collective self assembly. By varying features of our model, we identify a set of functions essential for the generation and stability of spindle bipolarity. When kinesin-5 motors are present, their bidirectionality is essential, but spindles can form in the presence of passive crosslinkers alone. We also identify characteristic failed states of spindle assembly, which are avoided by creation and maintenance of antiparallel microtubule overlaps.
Meredith received her BA in Physics from Princeton University in 1994, and then received a PhD in Physics from Harvard University in 2000. She now works as an Associate Professor in the Department of Physics at the University of Colorado at Boulder. He research interests are in biophysics and soft condensed matter physics. Her current projects address motor protein dynamics and microtubule length regulation, cytoskeletal active matter, mitotic spindle assembly and regulation, chromosome segregation in cell division, and disordered proteins in the nuclear pore complex. Among others, she has received an Alfred P. Sloan Fellowship in 2004, the NSF CAREER Award in 2009 and the NIH Quantitative Research Development Award in 2014.
Molecular Engineering and Sciences Seminar Series
This weekly seminar brings together students, faculty and invited guests from various disciplines across campus to explore current trends in molecular engineering and nanotechnology. It is a forum for active interdisciplinary discussions. These talks are open to the public and attract a diverse audience of students and faculty.