Objective
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.
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
- medical and health sciences basic medicine neurology neurodegenerative diseases dementia alzheimer
- natural sciences biological sciences biochemistry biomolecules proteins
- natural sciences physical sciences optics microscopy
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Keywords
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Programme(s)
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
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HORIZON.1.2 - Marie Skłodowska-Curie Actions (MSCA)
MAIN PROGRAMME
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Topic(s)
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Funding Scheme
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
HORIZON-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European Fellowships
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Call for proposal
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
(opens in new window) HORIZON-MSCA-2023-PF-01
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Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.
3584 CS Utrecht
Netherlands
The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.