Project 463633

Every second, many millions of cells in our bodies divide. Cell division is essential to maintain the health of our tissues and organs. Should a cell fail in its division attempt this could lead to cancer. Fortunately, sophisticated mechanisms have evolved to ensure that cell division is (virtually) error-free, but we do not properly understand these mechanisms in molecular terms for any cell type. To divide, cells build a dynamic structure on the inside of their membrane called the "contractile ring". This ring is made of various types of cables, strapped together into a meshwork that somehow cooperate to pull the cell membrane inwards, like a purse string. A switch-like protein called Rho controls the formation of the contractile ring by recruiting a network of other proteins. Our work suggests that one of these, Anillin, acts as a central organiser that can associate with different cables while also allowing them to separate as the ring closes. But the details of how this works remain a mystery. This project will primarily use cells from the fruitfly (a model organism with a simpler set of genetic instructions, yet the same division machinery as human cells) to determine precisely how Rho, Anillin and other key players within this "contractile ring" influence each other. We will determine how Anillin connects to different cables, specifically disrupt those connections in living cells, and monitor the effects on the different cables and on the cell division process by video- microscopy. This will help uncover how normal tissues grow and develop but also how cancers can arise, because they often exhibit defects in the cell division process. Also, for unknown reasons, Anillin is over-activated in some of the most aggressive cancers, such as breast and pancreatic cancer. Understanding how Anillin functions may provide clues on how to treat these cancers.