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Biomolecular regulation with interlocked cyclic oligonucleotides

Project description

Precise cellular control with biohybrid molecules

Living systems perform countless functions with great precision. In diagnostics, medicine, and biotechnology there is a need for tools that overcome certain limitations that natural systems present in terms of efficiency and stability. To address this issue, the ERC-funded BioRIcON project aims to develop a new class of biohybrid interlocked molecules (BIMs) that combine small cyclic oligonucleotides mechanically bound to other biomolecules. These BIMS mimic protein-like functions and can operate in complex biological environments. The key objective is to create smart molecular switches and enable precise biomolecular regulation inside cells. BIMs are expected to provide a breakthrough in biosensing and biomedicine.

Objective

Developing molecules that display protein-like functions and efficiently operate in complex biological environments, e.g. cells, is a grand challenge in chemistry.
The aim of BioRIcON is to develop a novel class of biohybrid interlocked molecules (BIMs) that mirrors the function of proteins and enables precise biomolecular regulation. Despite the advances of interlocked molecules, often compared to biological motors, their use in cellular or in vivo settings pales compared to their natural counterparts. BioRIcON comprises an entirely new concept in artificial biology and biomolecular control by yielding BIMs that contain dynamic components ultimately designed to efficiently actuate in cells with high spatio-temporal resolution. I will develop molecular switches and motors using small cyclic oligonucleotides (cONs) that will be mechanically bound – like links in a chain - to other biomolecules to regulate their function. The resulting BIMs merge the best of two worlds: i) the programmability and biocompatibility features of oligonucleotides, and ii) the robustness and scalable production of synthetic mechanically interlocked systems.
The goals of BioRIcON include: i) developing BIM-based shuttles and motors that can operate effectively in biological environments, integrate, and react to cellular cues and signaling; ii) exploring mechanical interlocking for reversible molecular display and protection against degradation; iii) implementing BIMs in biomolecular regulation, focused on reversible oligonucleotide-based therapies.
BioRIcON will significantly advance the toolbox of biomimetic systems and enable their integration in processes such as gene regulation and protein expression. BIMs use mechanical interlocking to reversibly protect and control biomolecular function in an adaptative manner, with a focus on RNA regulation which will help unravel the mechanisms of fundamental biological processes and hold enormous innovative potential in biosensing and biomedicine.

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HORIZON-ERC - HORIZON ERC Grants

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(opens in new window) ERC-2024-COG

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Host institution

AARHUS UNIVERSITET
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.

€ 1 999 799,00
Address
NORDRE RINGGADE 1
8000 Aarhus C
Denmark

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Region
Danmark Midtjylland Østjylland
Activity type
Higher or Secondary Education Establishments
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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.

€ 1 999 799,00

Beneficiaries (1)

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