Structure and molecular mechanism of the Augmin complex in mitotic spindle assembly

Accurate separation of genetic material into two daughter cells is a main objective of cell division. Failure in this process results in genome instability and cancer. The mitotic spindle is the apparatus in the cell that fulfils this task. The spindle has two poles to define the positions of two daughter cells. Filament-like structures called microtubules emanate from the poles, search and capture chromosomes and align them in the centre into a ready-to-separate state. The spindle then provides force to pull apart sister chromatids towards two opposite poles. Spindle assembly involves hundreds of proteins. The augmin complex, composed of eight distinct proteins, plays a critical role in spindle assembly and its depletion causes decreased microtubule density in the spindle and defects such as formation of multipolar spindles.

I propose to determine the atomic structure of human augmin complex and augmin-microtubule complex by cryo-electron microscopy, which will provide important insights into how this complex works. I will also explore how the augmin complex is regulated by mitotic phosphorylation.

Since the augmin complex is essential for proper formation of the spindle for cell division, it could be a new target to develop small-molecule-inhibitor drugs to treat cancer.