Molecular receptors enrich methylated and acetylated peptides for ultra-sensitive proteomics to explore the hidden modified proteome in disease

Project Information

ENRICH

Grant agreement ID: 101131120

DOI

10.3030/101131120

EC signature date 23 August 2023

Start date 1 January 2024

End date 31 December 2027

Funded under

• Marie Skłodowska-Curie Actions (MSCA)

Total cost

No data

EU contribution

€ 1 545 600,00

Coordinated by

UNIVERSITA DEGLI STUDI DI PARMA
Italy

Periodic Reporting for period 1 - ENRICH (Molecular receptors enrich methylated and acetylated peptides for ultra-sensitive proteomics to explore the hidden modified proteome in disease)

Reporting period: 2024-01-01 to 2025-12-31

Summary of the context and overall objectives of the project

ENRICH is a Horizon Europe – MSCA Staff Exchanges project built around a practical need in protein analysis: post-translational modifications (PTMs) on histone proteins are biologically important, but they are often difficult to detect and study because of their low concentration and complex matrices. Enrichment steps are therefore essential, yet existing approaches are not always selective, robust, or easy to adapt to different PTMs.
The overall objective of ENRICH is to develop and test new enrichment tools specifically aimed at histone PTMs, by combining designed “host” systems (molecules meant to bind specific targets) with functionalised nanoparticles. The project brings together complementary expertise across the partners to prepare the hosts, synthesise and functionalise the nanoparticles, characterise the resulting hybrid materials, and assess their performance in representative enrichment experiments using commercially available histone proteins.
In the short term, ENRICH will deliver prototype materials and reproducible, non-sensitive procedures to improve the consistency of histone PTM enrichment. In the medium term, this is expected to improve the reliability and comparability of downstream analyses across laboratories. In the long term, the tools and protocols developed can support further research in epigenetics and chromatin biology and, where relevant, method development in applied R&D.
ENRICH also follows responsible research practices, with attention to ethics, data management, and clear communication of the project’s goals and results to non-specialist audiences.

Work performed from the beginning of the project to the end of the period covered by the report and main results achieved so far

During the reporting period, ENRICH concentrated on the work needed to develop new materials for the selective enrichment of post-translational modifications (PTMs) on histone proteins. The activities covered the preparation of tailored supramolecular host systems, their integration onto nanoparticle platforms, and the start of validation in enrichment experiments under representative conditions.
The host molecules were successfully prepared and characterised using standard analytical methods, providing a set of candidates for PTM-oriented recognition. In parallel, nanoparticles were produced and functionalised with the selected hosts using reproducible procedures, and physicochemical characterisation confirmed successful functionalisation and material stability.
Preliminary enrichment experiments are currently ongoing using the developed functionalised nanoparticles and commercially available histone proteins. These tests are intended to benchmark performance and selectivity across conditions and to guide the selection of the most promising host–nanoparticle combinations for the next phase. Overall, the work completed in this period created the technical basis for systematic validation and optimisation of histone PTM enrichment within the consortium.

Progress beyond the state of the art and expected potential impact (including the socio-economic impact and the wider societal implications of the project so far)

During the reporting period, ENRICH produced early results beyond the state of the art by establishing a modular enrichment concept in which tailored supramolecular host systems are immobilised on nanoparticles to target histone PTMs. Compared with conventional enrichment strategies, this platform is designed to be tunable (by changing the host), practical to handle (through the nanoparticle format), and suitable for systematic comparison of different host–material combinations. Importantly, the approach is also being developed as an ethical alternative to enrichment methods that rely on animal-derived antibodies, by aiming to deliver synthetic, reproducible binders that can reduce dependence on animal sources while maintaining high performance.
The expected impact is improved selectivity and consistency in histone PTM enrichment, leading to more reliable downstream analyses and better comparability of results across laboratories. In the longer term, the same platform can be adapted to additional PTMs by modifying the host chemistry and functionalisation strategy.
Further uptake will require expanded validation and benchmarking against established workflows, together with clear protocols and quality-control criteria to support inter-laboratory reproducibility. As the most promising combinations emerge, application-oriented demonstrations and an assessment of IPR/freedom-to-operate will help define realistic routes for broader use, including potential engagement with external users or suppliers where appropriate.

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