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Single molecule protein sequencing using biological nanopores

Project description

A novel method for protein sequencing

Post-translational modifications (PTM) endow proteins with extensive functional variation paramount for living organisms. However, detection of these modifications by sequencing or mass spectrometry comes with certain limitations. Both techniques are labour-intensive, require extensive sample preparation and cannot account for low-abundance proteins or provide information at the single-cell level. Scientists of the EU-funded SMPSBN project propose to develop a method similar to nanopore DNA sequencing for determining PTMs in a high-throughput manner and with single-molecule sensitivity. Once materialised, this technology is expected to revolutionise proteomics research and pave the way for its use in the clinic.

Objective

Despite the importance of post-translational variation to the function of proteins in a living organism, sequencing proteins to study these variations is still a costly and time-consuming process, with intrinsic limitations. Protein sequencing and detection of post-translational modifications (PTMs) by mass spectrometry, the current gold standard, requires extensive sample preparation and large sample sizes, and possesses a limited dynamic range with respect to sample concentration. These limitations severely restrict its application to biological and clinical problems. A robust method for sequencing proteins and detecting PTMs at the single-molecule level would be revolutionary for proteomics research, allowing biologists to quantify low-abundance proteins as well as distributions and correlations of PTM patterns, all at a single-cell level. I propose a first-of-kind method for protein sequencing with applications in fundamental biology, cancer immunotherapy, and pharmaceutical development. This method uses biological nanopores in a manner similar to nanopore DNA sequencing, an established single-molecule sequencing technology capable of high throughput and single-molecule sensitivity. Developing this method for protein sequencing comes with many significant challenges, which will be addressed over the course of the proposed research.

Fields of science (EuroSciVoc)

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Programme(s)

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Topic(s)

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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.

MSCA-IF-EF-ST - Standard EF

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Call for proposal

Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.

(opens in new window) H2020-MSCA-IF-2019

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Coordinator

TECHNISCHE UNIVERSITEIT DELFT
Net EU contribution

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.

€ 187 572,48
Total cost

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.

€ 187 572,48
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