Project description
Accelerating drug discovery with DNA libraries
Drug discovery requires screening vast numbers of molecules against biological targets, a process that is costly, time-consuming and chemically limited with conventional methods. DNA-encoded libraries address this by attaching unique DNA barcodes to millions of compounds, enabling simultaneous screening at unprecedented scale. With the support of the Marie Skłodowska-Curie Actions programme, the ADES-DELi-MCR project transforms DNA-encoded library technology by integrating a precise, tip-free liquid handling method called acoustic droplet ejection with multicomponent chemical reactions. The idea is to generate structurally complex molecules in nanolitre volumes, reducing reagent consumption dramatically while expanding chemical diversity to billions of compounds. This sustainable high-throughput platform will be validated against both purified targets and cells, aiming to identify novel drug candidates across various diseases.
Objective
DNA-encoded libraries (DELs) allow the screening of millions to billions of small molecules via DNA barcodes that record each compound’s synthesis. Conventional DEL workflows rely on simple reactions (e.g. amide coupling, Suzuki) in microliter volumes using tip-based robots, limiting chemical diversity, sustainability, and throughput. This project overcomes these constraints by integrating acoustic droplet ejection (ADE), multicomponent reactions (MCRs), and DEL synthesis for the first time. ADE enables nanoliter-scale, tip-free transfers with high precision, drastically reducing reagent consumption and time. Coupled with MCR chemistry, such as Ugi-4CR, libraries of 10⁸–10⁹ structurally complex, 3D-rich molecules can be generated in hours under DNA-compatible conditions. The workflow includes ADE-based synthesis, enzymatic DNA ligation, and selection assays—achievable in a single afternoon. Biological validation will employ both target-based pull-down/NGS screening and proteome-wide selections in whole-cell lysates using covalent capture strategies. This dual approach ensures robust identification of ligands active in purified and complex systems. The CATRIN/IMTM Dömling lab offers unparalleled infrastructure, including advanced automation (Echo, TECAN EVO), UPLC-MS, NGS, and the world’s largest isocyanide collection, supported by expertise in synthetic chemistry, DEL screening, and MCR methodology. A provisional patent has been filed, and strong industrial interest underscores the platform’s commercial potential. This sustainable, high-throughput strategy redefines DEL synthesis, enabling AI-driven design loops and positioning Palacky University as a leader in next-generation drug discovery.
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
- engineering and technology mechanical engineering mechatronics automation
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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)
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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
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Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
(opens in new window) HORIZON-MSCA-2025-PF
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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.
771 47 Olomouc
Czechia
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.