Francis Barr

I lecture Biochemistry undergraduates on basic cell biological mechanisms and also supervise doctoral students in the Department of Biochemistry.

The human body is made from billions of cells, many of which are continuously replenished throughout our lives through the processes of cell growth and division. Each of these cells contains information in the form of DNA, packaged into chromosomes that contain the instructions governing how they will behave within our bodies. Mutation of the DNA and changes to those instructions alters the behaviour of cells and explains many diseases including cancers. I am interested in explaining how cell division operates with high fidelity to create normal cells, and the molecular processes that detect and prevent abnormal cells from growing when errors in the cell division process arise.

To address these questions, my research group uses a combination of different biochemical and cell biological approaches, as well as computational modelling to study the cellular mechanisms needed for the formation of new cells by the process of cell division. 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. Our current research projects study the function of an interlinked network of Aurora protein kinases and PPP family of protein phosphatases in dividing cells, and how they are localised and regulated. A major focus of this 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 through altered regulation of the essential kinetochore protein NDC80. 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. This work has shed important light on the mechanism of checkpoint signalling in mitosis, which is crucial for the high fidelity inheritance of chromosomes and maintenance of normal cells.

Sobajima T, Kowalczyk KM, Skylakakis S, Hayward D, Fulcher LJ, Neary C, Batley C, Kurlekar S, Roberts E, Gruneberg U, Barr FA. PP6 regulation of Aurora A-TPX2 limits NDC80 phosphorylation and mitotic spindle size. J Cell Biol. 2023 May 1;222(5):e202205117

Gerondopoulos A, Bräuer P, Sobajima T, Wu Z, Parker JL, Biggin PC, Barr FA, Newstead S. A signal capture and proofreading mechanism for the KDEL-receptor explains selectivity and dynamic range in ER retrieval. Elife. 2021 Jun 17;10:e68380

Holder, J., Mohammed, S., Barr, F., ‘Ordered dephosphorylation initiated by the selective proteolysis of cyclin B drives mitotic exit’ (2020)

Bancroft, J., Holder, J., Geraghty, Z., Alfonso-Pérez, T., Murphy, D., Barr, F., Gruneberg, U., ‘PP1 promotes cyclin B destruction and the metaphase-anaphase transition by dephosphorylating CDC20’ (2020)

Serena, M., Bastos, R.N., Elliott, P.R., Barr, F.A., ‘Molecular basis of MLKP2-dependenr Aurora B transport from chromatin to the anaphase central spindle’, The Journal of cell biology (2020) 219 (7)

Poser E, Caous R, Gruneberg U, Barr FA. Aurora A promotes chromosome congression by activating the condensin-dependent pool of KIF4A. J Cell Biol. 2019 Feb 3;219(2):e201905194

Gerondopoulos, A., Strutt, H., Stevenson, N.L., Sobajima, T., Levine, T.P., Stephens, D.J., Strutt, D., Barr, F.A., ‘Planar Cell Polarity Effector Proteins Inturned and Fuzzy Form a Rab23 GEF Complex’, Current biology (2019) 29 (19), 3323-3330

Hayward, D., Bancroft, J., Mangat, D., Alfonso-Pérez, T., Dugdale, S., McCarthy, J., Barr, F.A., Gruneberg, U., ‘Checkpoint signaling and error correction require regulation of the MPS1 T-loop by PP2A-B56’, The Journal of cell biology (2019) 218 (10), 3188-3199

Bräuer P, Parker JL, Gerondopoulos A, Zimmermann I, Seeger MA, Barr FA, Newstead S. Structural basis for pH-dependent retrieval of ER proteins from the Golgi by the KDEL receptor. Science. 2019 Mar 8;363(6431):1103-1107

Alfonso-Pérez T, Hayward D, Holder J, Gruneberg U, Barr FA. MAD1-dependent recruitment of CDK1-CCNB1 to kinetochores promotes spindle checkpoint signaling. J Cell Biol. 2019 Apr 1;218(4):1108-1117

Hayward D, Alfonso-Pérez T, Cundell MJ, Hopkins M, Holder J, Bancroft J, Hutter LH, Novak B, Barr FA, Gruneberg U. CDK1-CCNB1 creates a spindle checkpoint-permissive state by enabling MPS1 kinetochore localization. J Cell Biol. 2019 Apr 1;218(4):1182-1199