Mechanistic basis of force generation by the mitotic motor CENP-E

Prof Carolyn Moores (primary)
Biological Sciences
Dr Sarah McClelland (secondary)
Barts Cancer Institute


The mitotic spindle is a force-generating molecular machine, and is built from microtubules which work together with members of the kinesin motor superfamily. An imbalance in the tight regulation of mitosis or force generation within the spindle, results in incorrect chromosome segregation. Although segregation defects can lead to a range of cell fates, errors in mitosis can drive chromosomal instability, aneuploidy and cancer. The goal of this project is to use cryo-electron microscopy and biochemistry to reveal the force generation mechanism of the mitotic kinesin CENP-E, and to dissect the consequences of perturbation of this force generation on chromosomal segregation.


1. Peña A, Sweeney A, Cook AD, Locke J, Topf M, Moores CA. Structure of microtubule-trapped human kinesin-5 and its mechanism of inhibition revealed using cryo-electron microscopy. Structure 2020, 28(4): 450-457.
2. Locke J, Joseph AP, Peña A, Möckel MM, Mayer TU, Topf M, Moores CA. Structural basis of human kinesin-8 function and inhibition. Proc Natl Acad Sci U S A. 2017, 114(45):E9539-E9548.
3. Tovini L, McClelland SE Impaired CENP-E Function Renders Large Chromosomes More Vulnerable to Congression Failure. Biomolecules. 2019, 9(2) 44-55.
4. Worrall JT, Tamura N, Mazzagatti A, Shaikh N, van Lingen T, Bakker B, Spierings DCJ, Vladimirou E, Foijer F, McClelland SE. Non-random Mis-segregation of Human Chromosomes. Cell Rep. 2018, 23(11):3366-3380.
5. Craske B, Welburn JPI. Leaving no-one behind: how CENP-E facilitates chromosome alignment. Essays Biochem. 2020, 64 (2):313-324.

Molecules, cells and industrial biotechnology
Area of Biology
Cell BiologyStructural Biology
Techniques & Approaches
BiochemistryBiophysicsImage ProcessingMicroscopy / ElectrophysiologyMolecular BiologySimulation / Modelling