Mechanistic Cell Biology

It is barely visible to the naked eye and yet it contains everything that is necessary for the transmission of life from one generation to the next: an average human cell is only a few hundredths of a millimeter in size. The adult organism consists of several trillion cells. This miracle of growth is only possible through the repetition of a process that must perform perfectly each time: cell division, in which from one cell two identical daughter cells develop.

Although the steps of the process are roughly known it is unclear how cell division functions in detail. The process is highly complex. Prior to the division, as if by magic, hundreds of different building blocks converge with great accuracy in the cell and form a complex scaffold named the mitotic spindle, in which molecular motors play a crucial function. Meanwhile, still other proteins check whether the genetic material has correctly doubled, compacted, and sorted itself before the spindle may then neatly pull apart the chromosomes.

In our department we study the different molecular mechanisms that ensure that the genetic material is correctly distributed to the two daughter cells. For this purpose, we investigate the structure and function of a multitude of proteins that are involved – in particular those that comprise the kinetochore, the attachment site for the fibers of the spindle apparatus, and the proteins of the spindle assembly checkpoint that regulate the complex machinery of cell division. In our investigation we encountered proteins that recognize incorrectly assembled chromosomes and which halt the division process until the defects are corrected.

We just recently, analyzed and modelled the structure of the kinetochore. In the process we have discovered how the different kinetochore proteins work together to bind the chromosomes securely to the microtubules. By modelling the kinetochore we laid the foundation for further studies into the complex architecture and functionality of this vital structure. Our goal is to create an artificial model of cell division as a whole. "Because only when we can recreate these processes and cell components will we be in a position to truly understand how they work" (Prof. Dr. Andrea Musacchio).

A holistic understanding of these processes is very important because incorrect distribution of genetic material can cause developmental damage and abnormalities. Failure of the control mechanisms may even lead to the development of malignant tumors.

Cell Division

Left: Proper cell division, Right: Defective cell division (green: spindle apparatus, magenta: chromosomes )

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Maffini Pesenti I Vetter

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