Interlocking nanomechanics of kinesins and tubulins (360G-Wellcome-220387_Z_20_Z)

£1,639,257

Kinesin-microtubule systems transport intracellular cargo in eukaryotes and are essential for life. Recently, we discovered that dynamic microtubules can respond to kinesin by changing their conformation, lattice spacing, curvature and stability, and conversely that kinesin stepping can sense and respond to conformational shifts in the microtubule lattice. These insights fundamentally redraw our picture of the function of kinesin-microtubule transport systems. I now propose to dissect the mechanical mechanisms by which kinesins and microtubules instruct one another, using protein engineering combined with single molecule optical trapping at unprecedented resolution. Working with both wild-type and mutant kinesins and tubulins, principally from S. pombe, we will determine the structural requirements for different microtubule lattices to control kinesin substeps, backsteps and bidirectionality; and the converse requirements for kinesins to manipulate the conformation and fate of microtubules. Our experiments will reveal how tubulins communicate mechanically with one another and with kinesins. Illuminating the molecular mechanisms of active mechanical feedback in kinesin-microtubule systems will transform understanding of the transport machinery and open the way to improved chemical biological manipulation of its in vivo function.

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Grant Details

Amount Awarded 1639257
Applicant Surname Cross
Approval Committee Science Interview Panel
Award Date 2020-03-31T00:00:00+00:00
Financial Year 2019/20
Grant Programme: Title Investigator Award in Science
Internal ID 220387/Z/20/Z
Lead Applicant Prof Robert Cross
Partnership Value 1639257
Planned Dates: End Date 2025-05-31T00:00:00+00:00
Planned Dates: Start Date 2020-06-01T00:00:00+00:00
Recipient Org: Country United Kingdom
Region West Midlands