How does a cell construct its microtubule cytoskeleton? According to Feynman’s principle “what I cannot create, I do not understand”, my lab pursues this question by building the chromosome segregation machinery from scratch. I will first tell you how the microtubule framework is generated in a cell. Upon deciphering the function of the most important microtubule accessory proteins, I will present how we use those building blocks to reconstitute a spindle substructure in vitro and determine its building plan. Surprisingly, the spindle substructure relies on a protein condensate, which forms on the surface of a microtubule and arranges into a droplet pattern like a fluid.
By studying how the MT cytoskeleton is built, I hope to help explain how hundreds of proteins can self-assemble on the nm scale into a complex molecular machine 1000-fold larger than its constituents, a challenge for the biochemistry of the 21st century.