Cell division is a beautifully choreographed mechanical process in which the cell constructs a microscopic microtubule-based structure called the mitotic spindle. This facilitates physical segregation of chromosomes into daughter cells. Our work is focused on the kinetochore - an adaptive, multi-layered mechanochemical machines that assemble at the centromere of each sister chromatid and engage on their outer face with the plus ends of k-fibres, microtubule bundles that emanate from the spindle poles.
We are working to address three key questions in the cell division field: 1) how do kinetochore-microtubule interactions generate the pushing and pulling forces nessessary for chromosome movement? 2) How do kinetochores sense changes in attachment and convert this into checkpoint signals 3) What is the origin of chromosome segregation errors in human mitosis and meiosis? Approaches in the McAinsh lab include live-cell microscopy, computational image analysis, mathematical modelling and in vitro reconstitution.
Our work on chromosome segregation is supported by a Wellcome Investigator Award, Royal Society Wolfson Research Merit Award, the BBSRC and Leverhulme Trust and was recognised by award of the Hooke Medal in 2018.
Ensemble-Level Organization of Human Kinetochores and Evidence for Distinct Tension and Attachment Sensors.
Cell Rep. 2020 Apr 28;31(4):107535. doi: 10.1016/j.celrep.2020.107535. PMID: 32348762
Auckland P.A., Roscioli E. and McAinsh, A.D. (2020)
CENP-F stabilizes kinetochore-microtubule attachments and limits dynein stripping of corona cargoes.
Journal of Cell Biology 219:1623-1639 PMID: 32207772
*Pesenti M.E., *Prumbaum D., *Auckland P., Smith C.M., Faesen A.C., Petrovic A., Erent M., Maffini S., Pentakota S., Weir J.R., Lin Y.C., †Raunser S., †McAinsh A.D., †Musacchio A. (2018)
Reconstitution of a 26-Subunit Human Kinetochore Reveals Cooperative Microtubule Binding by CENP-OPQUR and NDC80
Molecular Cell 71:923-939.e10. PMID:30174292
- Auckland P.A., Clarke N., Royle S.J. and McAinsh, A.D. (2017)
Congressing kinetochores progressively load Ska complexes to prevent force-dependent detachment.
Journal of Cell Biology 216:1623-1639
Smith C.A., McAinsh A.D. and Burroughs N.J. (2016)
Human kinetochores are swivel joints that mediate microtubule attachments
Burroughs N.J., Harry E.F. and McAinsh A.D. (2015)
Super-resolution kinetochore tracking reveals the mechanisms of human sister kinetochore directional switching.