Project description
Biomimetic nanopores provide a peek inside the nucleus’ gatekeeper
Cells are the fundamental building blocks of living organisms, and in eukaryotes their activities rely heavily on the compartmentalisation afforded by membrane-bound organelles. The nucleus is no exception, controlling movement in and out with pores. Selectivity of small molecules is enabled by a tangled mesh of intrinsically disordered proteins in a central channel whereas large macromolecules depend on transporter proteins to move across the nuclear membrane. The biophysical mechanisms underlying selectivity and movement are not clear. With the support of the Marie Skłodowska-Curie Actions programme, the NTON project is developing a biomimetic nanopore platform for single-molecule studies to elucidate the enigmatic internal workings of the nuclear pore complex.
Objective
The nuclear pore complex (NPC) is the gatekeeper of the nucleus that regulates the flow of all molecules across the nuclear envelope. Remarkably, this ~40 nm wide pore is capable of efficient and fast transport while remaining highly selective. Its dense central channel is composed of a highly dynamic spaghetti-like mesh of intrinsically disordered proteins that allows small molecules to pass freely, whereas large macromolecules (>40 kDa) rely on specific transporter proteins that ferry their cargo across the pore. Even though various models have been proposed, the fundamental biophysical mechanism of nuclear transport and of the selectivity of the NPC has not been resolved yet. One of the main reasons that have hindered our progress in understanding nuclear transport is the lack of experimental techniques that can probe the structure and dynamics of the disordered proteins and transport receptors inside the NPC channel and during transport with sufficient spatiotemporal resolution. In the proposed action, I aim to establish a modifiable biomimetic platform for single-molecule investigations of nuclear transport. This interdisciplinary and innovative approach combines solid-state nanopores, coated with disordered proteins to mimic the nuclear pore, with optical detection in zero-mode waveguides and DNA origami nanotechnology. The proposed experiments will allow to monitor the translocation of single fluorescently labelled molecules through biomimetic NPCs with excellent sensitivity and specificity. I will use this platform to elucidate the biophysical principles that underlie the structure and selectivity of the NPC channel and the mechanism of active nuclear transport. The direct insights on the single-molecule level obtained by the results of this project will be crucial for our understanding of the molecular principles that govern nuclear transport.
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.
- natural sciences biological sciences genetics DNA
- natural sciences biological sciences biochemistry biomolecules proteins
- natural sciences biological sciences cell biology
- natural sciences biological sciences biophysics
- natural sciences biological sciences molecular biology
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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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H2020-EU.1.3. - EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions
MAIN PROGRAMME
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H2020-EU.1.3.2. - Nurturing excellence by means of cross-border and cross-sector mobility
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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.
MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF)
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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) H2020-MSCA-IF-2020
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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.
2628 CN DELFT
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.