Grant: Project Grant

We use biophysics- the intersection between biology and physics- to understand how cells use filaments called microtubules to carry out steps in cell division. Cell division is essential for developing embryos and to form new cells that sustain and repair healthy tissues/organs. Critically, both daughter cells must receive the correct number of chromosomes to survive. For this to happen one set of microtubules of the mitotic spindle attach to each pair of chromosomes, and the spindle is positioned prior to division by a separate, specialized set of microtubules. Microtubules intrinsically grow and shrink, an ability which cells coordinate and harness to generate force. We want to understand how the force produced by microtubules is harvested to move the spindle. Spindle positioning is important for many cells- stem cells in particular, as it determines how molecular information that specify cell fate is partitioned into daughter cells. We use a unicellular eukaryote that divides asymmetrically to form a small new daughter cell and a large mother cell to study this process. The +TIP body, a nanoscale assembly of proteins which positions the spindle. The +TIP body of this unicellular eukaryote is similar to microtubule associated "bodies" found in mammalian cells and is predicted to control microtubules through biophysical properties that emerge from its behavior as a liquid-like droplet. We will characterize biophysical properties of the +TIP body that coordinate the growth and shrinkage of an array of microtubules to allow them to work together to position the spindle, and measure how these are influenced by cellular regulators. In budding yeast, defective microtubules and spindle positioning prevent proliferation, but in multicellular organisms like humans it can lead to a plethora of diseases including cancer. Understanding the basic mechanisms by which microtubules are controlled has wide potential applications in detecting and treating these diseases.