Cell division & cancer
Be part of our leading cancer research by exploring the molecular machinery that controls cell division to allow rational cancer chemotherapy.
First, we have a hypothesis that the decatenation (unwinding) of DNA strands may be defective in cancers.
Because chromosomal instability gives less time in mitosis to sort out still-entangled chromosomes, we want to visualise topoisomerases during unstable mitoses to see whether decatenation is an issue for these cells, and whether it is affected by metabolic interventions that we know damage CIN cells.
Secondly, we are looking at ways in which cells sense that they are aneuploid.
We think there is a set of proteins that can detect when mitosis has gone wrong, and that these give a stress signal to the cell, to encourage it to die if necessary or at least stop dividing. We want to characterise this pathway to allow us to drive it to prevent the growth of aneuploid cancers.
The aim of our research is to understand the molecular machinery that controls cell division to allow rational cancer chemotherapy. Our work has identified key genes that control cell division and allowed us to see what they are doing in their normal setting: a live, developing animal.
We developed tools to observe the cellular machinery that divides cells in two at the end of mitosis, and to find the genes that regulate this process. This work is critical for an understanding of how normal growth works, but also to give us potential therapeutics that will allow us to block the uncontrolled cell division seen in cancer.
Using chromosomal instability to target cancer
Cancers are cells that not only divide too much, but also usually divide unstably, gaining and losing chromosomes. This chromosomal instability is not seen in normal dividing cells, so it may be an ideal chemotherapy target - something that we can affect in the cancer without hurting normal cells.
Using the advantages of Drosophila genetics, we have screened for gene knockouts that can kill unstably dividing cells, but not normal ones. We have found several ways to specifically kill cells with chromosomal instability, including targeting the JNK pathway, centrosomes or cell metabolism. We are now working to explain why unstably dividing cells are sensitive to these processes, and how we can best target them.