Robert Cross

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Professor Robert Cross

Director, Centre for Mechanochemical Cell Biology

Tel 024 761 51165 | Email R.A.Cross@warwick.ac.uk

Work in my lab focuses on the force generating mechanisms of kinesins and microtubules.

Google scholar | ORCID ID | Lab homepage

Plain English

Almost every one of the trillions of cells in your body contains a miniscule railway network. Work in my lab focuses on how these cellular railways work. We want to understand how the tracks (called microtubules) put themselves together, how the engines (called kinesins) move, and how the railway organises itself to successfully move traffic around the cell. Transport of cellular components by the microtubule railway is critically important in the lives of cells, for example for successful cell division, and for healthy brain function. Because the microtubule railway is so important, drugs that target the railway are key tools for medicine and agriculture.

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Professor Robert Cross

Director, Centre for Mechanochemical Cell Biology

Tel 024 761 51165 | Email R.A.Cross@warwick.ac.uk

Work in my lab focuses on the force generating mechanisms of kinesins and microtubules.

Google scholar | ORCID ID | Lab homepage

Plain English

Technical Summary

Work in my lab focuses on the force generating mechanisms of kinesins and microtubules. Using a combination of protein engineering, rapid kinetic analysis and single molecule microscopy, we have shown for example that dimeric kinesin motors can be driven to walk backwards under load, that ATP binding controls walking, and that the individual mechanical steps of the motor happen on the microsecond timescale. We have worked extensively with microtubules in the fission yeast S. pombe, and were the first to describe the in vivo dynamics of the interphase S. pombe microtubule cytoskeleton. We have developed a biochemical purification for S. pombe tubulin and have used this to understand how plus end tracking proteins influence the structure and dynamics of S. pombe microtubules. In order to address these problems, we have developed our own optical microscopes. Recently, we harnessed this experience to construct the WOSM (Warwick Open Source Microscope), a super-stable open source platform for super resolution microscopy and optical trapping. The WOSM is already the basis of a number of collaborative projects at Warwick and elsewhere. Our current work is aimed at digging deeper into the fundamental mechanisms that allow kinesin motors to exert directional force on tubulin, and into the operation of these mechanisms in teams of kinesins interacting with dynamic microtubules. We are also aiming, via collaborations, to understand how kinesin-tubulin interactions contribute to the patterning of force generation in cells. Forces generated by kinesins and microtubules drive much of the self-organisation behaviour of eukaryotic cells. Understanding the force-generating mechanism is therefore important, not just for fundamental science, but also for the development of improved chemical biology approaches to a range of important medical and agricultural problems.

Selected publications

ORCID: https://orcid.org/0000-0002-0004-7832

McHugh, T., Drechsler, H., McAinsh, A.D., Carter, N.J. & Cross R.A. (2018)
Kif15 functions as an active mechanical ratchet.
Mol Biol Cell. mbcE18030151. doi: 10.1091/mbc.E18-03-0151. [Link]

Peet, D.R., Burroughs, N.J. & Cross, R.A. (2018)
Kinesin expands and stabilizes the GDP-microtubule lattice.
Nat Nanotechnol doi: 10.1038/s41565-018-0084-4 [Link]

Alonso,M.C., Drummond, D.R., Kain, S., Hoeng, J., Amos, L.A. & Cross, R.A. (2007)
An ATP-gate controls tubulin binding by the tethered head of kinesin-1
Science 316 120-123

Carter N.J. & Cross R.A. (2005)
Mechanics of the kinesin step
Nature 435 308-12