Manuela Richter

UC San Francisco

“Building the Machine of Life: Kinetochore-fiber lengths are maintained locally but coordinated globally by poles in the mammalian spindle”

I study the biophysics and self-organization of complex biological structures, focusing on the mitotic spindle – the cellular machine that is fundamental to life, ensuring proper chromosome segregation and cell division.

ABSTRACT

Nearly two trillion of our cells divide every day, and they need to ensure their genetic material is properly duplicated and separated into each new cell created, or risk cell death, cancer, and developmental disorders. How do cells make sure they segregate their chromosomes perfectly every time they divide? I study the cellular machine responsible for this – the mitotic spindle. Using molecular techniques, biophysics tools, and advanced microscopy, I probe how the complex architecture of the spindle emerges from simple building blocks. In particular, I focus on how individual spindle fibers “know” their length. I can molecularly disconnect spindle fibers from the structure holding them together (the pole) and find that they still set the same mean length. I can biophysically cut a single spindle fiber and watch it regrow back to the length of others, even without a pole connection. Thus, we conclude that spindle fibers have an “innate” sense of how long to be, and that spindles – and possibly other complex biological structures – are built of locally-regulated individual components, but coordinated globally across space and time.
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