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TuningTracks

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Tuning the Tracks: Resolving the interplay between microtubule lattice conformat...

Tuning the Tracks: Resolving the interplay between microtubule lattice conformation and kinesin-1 selectivity using cryo-EM Kinesin-1 transports cellular cargos along microtubules as part of neuronal transport. The localisation of kinesin-1 in neurons is tightly controlled to ensure the coordinated delivery of specific cargoes to the regions where they... ver más

14/04/2026

188K€

Presupuesto del proyecto: 188K€

Líder del proyecto

UNIVERSITEIT UTRECHT No se ha especificado una descripción o un objeto social para esta compañía.

TRL 4-5

Financiación concedida El organismo HORIZON EUROPE notifico la concesión del proyecto el día 2024-03-12

HORIZON-MSCA-2023-PF-01-01: MSCA Postdoctoral Fellowships 2023 ExpectedOutcome:Project results are expected to contribute to the following outcomes:

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No hay información privada compartida para este proyecto. Habla con el coordinador.

1 Participantes

187.62K€ | Lider

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Duración del proyecto: 25 meses Fecha Inicio: 2024-03-12
Fecha Fin: 2026-04-14

Líder del proyecto

UNIVERSITEIT UTRECHT No se ha especificado una descripción o un objeto social para esta compañía.

TRL 4-5

Presupuesto del proyecto 188K€

Descripción del proyecto Kinesin-1 transports cellular cargos along microtubules as part of neuronal transport. The localisation of kinesin-1 in neurons is tightly controlled to ensure the coordinated delivery of specific cargoes to the regions where they are required. One mechanism of control is through microtubule regulation, but the details of this are not well understood. It has recently been shown that microtubule lattice spacing influences kinesin-1 localisation in U2OS cells. However, the role lattice spacing plays in neuronal transport is unclear. This project aims to investigate features of kinesin-1 based neuronal transport on multiple scales. First, this project aims to use cryo-electron microscopy (cryo-EM) to elucidate how kinesin-1 binds to specific microtubule subsets. I will resolve the high-resolution cryo-EM structure of a dimeric kinesin-1 construct (stableMARK) bound to microtubules with different lattice states. This will explain its lattice specificity and help uncover the mechanics of kinesin-1 walking. Secondly, I will map microtubule lattice spacing in neurons using in situ cryo-electron tomography to establish the lattice diversity within this complex microtubule network. Thirdly, I will use cryo-correlative light electron microscopy and stableMARK to determine if lattice spacing influences kinesin-1 localisation in neurons. This project will answer key biological questions on cytoskeletal transport, which will be applicable to other microtubule-based motors and microtubule associated proteins. Defects in kinesin-1 based transport have been implicated in multiple neuropathies, such as Alzheimer’s disease, therefore further understanding of how neuronal transport is controlled will help uncover the mechanism of these diseases.

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