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Andrew McAinsh

Technical Summary

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.

chromsegWe 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 Wellcome & BBSRC and recognised by award of the Hooke Medal in 2018 and Royal Society Wolfson Research Merit Award in 2015.

Latest works:

Currie CE, Ford E, Benham Whyte L, Taylor DM, Mihalas BP, Erent M, Marston AL, Hartshorne GM, McAinsh AD.
The first mitotic division of human embryos is highly error prone.
Nat Commun. 2022 Nov 8;13(1):6755. doi: 10.1038/s41467-022-34294-6. PMID: 36347869 Free PMC article.

McAinsh AD, Marston AL.
The Four Causes: The Functional Architecture of Centromeres and Kinetochores.
Annu Rev Genet. 2022 Nov 30;56:279-314. doi: 10.1146/annurev-genet-072820-034559. Epub 2022 Sep 2.
PMID: 3605565

Sen O, Harrison JU, Burroughs NJ, McAinsh AD.
Kinetochore life histories reveal an Aurora-B-dependent error correction mechanism in anaphase.

Dev Cell. 2021 Dec 20;56(24):3405. doi: 10.1016/j.devcel.2021.11.023.

Roscioli, E., Germanova, T.E., Smith, C.A., Embacher, P.A., Eren,t M., Thompson, A.I., Burroughs, N.J., McAinsh, A.D.
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