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Legonucleotides for detection

Project description

LEGO-like molecular recognition systems

Biosensors are analytical devices that combine a biological sensing element with a transducer to detect, monitor and quantify specific molecules or changes in biological systems. These devices have found applications in medical diagnostics, environmental monitoring, food safety, and biotechnology. Funded by the European Research Council, the Chem2Sense project will address the challenge of developing universal molecular recognition systems. The project proposes an innovative approach using chemically modified oligonucleotides attached to small molecules in a dynamic combinatorial library. These LEGO brick-like aptamers will overcome previous technical limitations in design and with the help of AI are expected to enhance process versatility and increase potential applications.

Objective

Sensors have a vital importance on human life, detecting diseases or contaminants that endanger the environment. A widely pursued challenge has been to develop universal biosensors with the flexibility to detect molecules regardless of their size. Antibodies have been used to fulfill this aim, but single-stranded oligonucleotides (aptamers) interact efficiently with targets and have also been proposed as an alternative. However, aptamers lack the ability for versatile functionalization to tune affinities, and they suffer from highly complex selection and identification.
Chem2Sense proposes an interdisciplinary approach to overcome these obstacles. My hypothesis is that a new strategy based on the reversible conjugation of aptamers with small molecules will remove barriers in designing universal biosensors. Chem2Sense aims to redesign the aptamer concept with flexible oligolegonucleotides and a cutting-edge nanopore sequencing methodology. The two objectives will be to develop chemically modified nucleotides as lego-bricks to build high-affinity aptalegomers, and to develop a ground-breaking sequencing methodology using artificial intelligence to boost aptalegomer identification. The proposed legonucleotides are synthetic nucleotides that reversibly attach small molecules in a dynamic combinatorial library. After challenging a vast library against a target, a Darwinian chemical selection will occur, leading to the best fit, the aptalegomer, a high-affinity oligonucleotide of natural and conjugated legonucleotides.
Therefore, the objective of Chem2Sense is to create a ground-breaking methodology that overcomes significant obstacles in aptamers’ development, providing a powerful synergy between novel chemical aptalegomers generation and a direct method for selection/identification using the latest advances in oligonucleotide sequencing. Chem2Sense will bring highly sensitive and versatile aptalegomers to a broad range of vital applications.

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HORIZON-ERC - HORIZON ERC Grants

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Call for proposal

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(opens in new window) ERC-2023-COG

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Host institution

AGENCIA ESTATAL CONSEJO SUPERIOR DE INVESTIGACIONES CIENTIFICAS
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.

€ 1 999 144,00
Address
CALLE SERRANO 117
28006 MADRID
Spain

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Region
Comunidad de Madrid Comunidad de Madrid Madrid
Activity type
Research Organisations
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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.

€ 1 999 144,00

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