Prof Francis Barr
Astronomical numbers of cells have to be produced without error during our lives. Each of those new cells is generated by division of a pre-existing cell. We want to understand how that process works, and how mistakes give rise to diseases such as cancers.
Prof Francis Barr
Molecular mechanisms of cell division
Why is cell division important?
Cell division is fundamental to the creation and maintenance of our bodies. Throughout our adult lives, cell division is needed to replenish old and damaged cells in our skin, the lining of the gut or blood, and to create cells to fight infection as part of the immune response. Each of these cells must inherit an undamaged copy of the genome in the form of chromosomes, as well as essential membrane organelles such as mitochondria needed to produce energy, and the endoplasmic reticulum and Golgi apparatus needed for cell growth and to make antibody proteins that help fight infection.
The Barr lab uses cell and structural biology, as well as computational modelling to explain the cellular mechanisms needed for cell division and the function of membrane organelles. We also explore the consequences of dysregulation of these pathways in human cancers and other diseases. By researching these molecular mechanisms we contribute to the identification of targets that can be exploited therapeutically in these disorders. These projects are only possible through the continued funding and support of Cancer Research UK, the Wellcome Trust and the BBSRC.
Our current research projects study the function of an interlinked network of protein kinases and phosphatases in dividing cells, and how they are localised and regulated. A major focus of our work has been the function of the PPP family of protein phosphatases in human cells: PP1, PP2A and PP6. We have shown how PP6 controls the activity of the kinase Aurora A, and found that this pathway is dysregulated in human cancers such as melanoma, where it drives genome instability and DNA damage. One of our aims is to exploit this pathway to specifically target and selectively kill tumours with amplified Aurora A kinase. Our other work has explained how regulation of the PP2A-B55 phosphatases contribute important timing properties to the metaphase to anaphase transition, and identified and modelled the behaviour of key substrate proteins in the cell. Most recently we have shown how the Aurora B kinases binds to chromosomes and is localised in cells undergoing cytokinesis. You find out more about some of our recent publications in the list below.
Barr Lab Website: https://fablab.web.ox.ac.uk