Cell division is fundamental for growth and development of an organism. As millions of cell divisions have to occur before an organism reaches its final size and even in a fully-grown organism cells have to be constantly replaced, high fidelity of cell division and, in particular, chromosome segregation is critical to prevent diseases such as cancer. Our goal is to elucidate how cells ensure faithful chromosome segregation, and which aspects of this go awry in cancer cells.
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Mitotic HeLa cell. Different parts of the cellular mitotic machinery have been indicated.
Live cell imaging of a dividing HeLa cell expressing histone H2B-mCherry and alpha-tubulin-eGFP.
Normal cell division versus defective cell division.
Research in the laboratory focuses on understanding how equal chromosome segregation is achieved during mammalian cell division and how aberrant ploidies, often observed in tumour cells, change the requirements for successful mitosis. Faithful genome segregation requires the attachment of the paired sister chromatids making up each chromosome to spindle microtubules from opposite poles of the mitotic spindle, as only this arrangement will result in accurate division of the sister chromatids to the progeny cells at the metaphase-to-anaphase transition. The correct attachment of the chromosomes to the microtubules via kinetochores is a critical prerequisite for successful chromosome segregation and is monitored by two crucial, interlinked cellular surveillance systems: error correction and spindle assembly checkpoint signalling. Error correction refers to the turn-over of microtubule-kinetochore attachments of incorrect geometries, transiently generating unattached kinetochores. Spindle assembly checkpoint signalling is intimately connected to the error correction process and delays cell cycle progression into anaphase until any incorrect or missing microtubule-kinetochore attachments have been fixed. These mechanisms are essential for safeguarding the success of chromosome segregation but many aspects of the underlying molecular biology remain poorly understood, and are the focus of our research.
Our main research questions are:
To study these processes, we use mammalian tissue culture cells of different genetic backgrounds and ploidies. We employ a combination of molecular biology, including CRISPR/Cas9 genetic modification of cell lines, biochemical and cell biological methods, imaging of both live and fixed cells, as well as mass spectrometry and in vitro kinase and phosphatase assays for our research.
Research in the Gruneberg lab is funded by a Cancer Research UK Discovery Programme grant.
2022
MPS1 localizes to end-on microtubule-attached kinetochores to promote microtubule release.
Hayward, D., Roberts, E. and Gruneberg, U.
Curr Biol. – 32(23): 5200-5208.e8.
2021
The association of Plk1 with the astrin-kinastrin complex promotes formation and maintenance of a metaphase plate.
Geraghty, Z., Barnard, C., Uluocak, P. and Gruneberg, U.
J Cell Sci. – 134(1): jcs251025.
2020
PP1 promotes cyclin B destruction and the metaphase-anaphase transition by dephosphorylating CDC20.
Bancroft, J., Holder, J., Geraghty, Z., Alfonso-Perez, T., Murphy, D., Barr, F.A. and Gruneberg, U.
Mol Biol Cell – 31(21): 2315-2330.
2019
Checkpoint signaling and error correction require regulation of the MPS1 T-loop by PP2A-B56.
Hayward, D., Bancroft, J., Mangat, D., Alfonso-Perez, T., Dugdale, S., McCarthy, J., Barr, F.A., and Gruneberg, U.
J Cell Biol. – 218(10): 3188-3199.
2019
Orchestration of the spindle assembly checkpoint by CDK1-cyclin B1.
Hayward, D., Alfonso-Perez, T. and Gruneberg, U.
FEBS Lett. – 593(20):2889-2907.
2019
CDK1-CCNB1 creates a spindle checkpoint-permissive state by enabling MPS1 kinetochore localization.
Hayward, D., Alfonso-Perez, T., Cundell, M.J., Hopkins, M., Holder, J., Bancroft, J., Hutter, L.H., Novak, B., Barr, F.A. and Gruneberg, U.
J Cell Biol. – 218(4): 1182-1199.
2019
MAD1-dependent recruitment of CDK1-CCNB1 to kinetochores promotes spindle checkpoint signaling.
Alfonso-Perez, T., Hayward, D., Holder, J., Gruneberg, U. and Barr, F.A.
J Cell Biol. – 218(4): 1108-1117.
2014
PP2A-B56 opposes Mps1 phosphorylation of Knl1 and thereby promotes spindle assembly checkpoint silencing.
Espert, A., Uluocak, P., Bastos, R.N., Mangat, D., Graab, P. and Gruneberg, U.
J Cell Biol. – 206(7): 833-42.
A changing view of how MPS1 initiates the Spindle Assembly Checkpoint
November 2022
A new study published in Current Biology by the Gruneberg lab advances our understanding of the mechanisms by which cells correct mistakes during chromosome segregation. 3.8 million duplicated genomes have to segregate equally into daughter cells every second in our body to maintain normal cell and tissue function. Any problem in the chromosome segregation process...
Prestigious BSCB prize for Iona Manley
May 2022
The Gruneberg lab student was recognised with the BSCB Young Cell Biologist of the Year Prize At the recent BSCB/BSDB joint spring conference at the University of Warwick, Iona Manley, a 4th year PhD student in the Gruneberg lab, won this year’s BSCB Young Cell Biologist of the Year Prize with her poster “A novel...
Prof Ulrike Gruneberg awarded a Discovery Programme Award by CRUK
February 2022
These prestigious 5-year grants from Cancer Research UK (CRUK) “provide long-term support for outstanding established scientists in basic or translational research fields” under CRUK’s overarching aim: “to bring forward the day when all cancers are cured”. Prof Gruneberg first established her research group at the University of Liverpool, joining the Dunn school in 2013, and...
Three Dunn School academics recognised with Full Professor title
December 2021
Many congratulations to Omer Dushek, Fumiko Esashi and Ulrike Gruneberg We are delighted to announce that three Dunn School group leaders were recognised in this year’s University of Oxford Recognition of Distinction exercise. Omer Dushek is now Professor of Molecular Immunology. His group investigates the immunology of T cell receptor signal integration, at the interface...