Associate Prof Catherine Pears

Cell Signalling

Histone modifications cause changes in chromatin structure to regulate gene expression. We study the importance of these during development and in differentiation of different cell types. The eukaryotic social amoeba Dictyostelium discoideum has similar histone modifications to mammals but it is easier to study their role. Dictyostelium lives as single cells when feeding but forms a multicellular organism when starved, with two main cell types – spores that can survive starvation and stalk cells that help disperse these spores. Dictyostelium has only a few histone genes, unlike mammals, and fewer versions of the modifying enzymes, so we can mutate them to stop them being modified and follow the consequences for development and for forming the different cell types in the right places. We also use genetic and biochemical methods to study the signalling pathways that bring about the modifications. DNA carries the genetic information so it is important to make sure it doesn’t accumulate damage. Histones are modified at sites of damaged DNA and recruit proteins needed to repair it correctly. Dictyostelium is very resistant to DNA damage, using similar pathways to human cells, and we study Dictyostelium to understand how ADP-ribosylation of histones regulates DNA repair. Inhibitors of the enzymes that add ADP-ribose are used to treat some forms of breast and ovarian cancer, so mutating the histones in Dictyostelium and studying the consequences for DNA repair when ADP-ribosylation cannot happen, will help develop more specific drugs to treat these diseases.

For more information, please see: https://pears.web.ox.ac.uk/