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

Project description

Reliable, cost-effective and ultrasensitive detection of modified histones

Histones are proteins that attach to the DNA (chromosomes) in the nucleus and help to package and organise it. Once in the cytoplasm, post-translational modifications (PTMs) to histones are essential for many cellular processes including transcription and DNA repair. Understanding histone PTMs is important to preventing and treating diseases including cancer. Mass spectrometry (MS) relying on an expensive enrichment step that lacks reproducibility is commonly used to identify histone PTMs across the proteome. With the support of the Marie Skłodowska-Curie Actions programme, the ENRICH project aims to use functionalised nanoparticles to enrich PTM-containing peptides obtained with proteolytic digestion for subsequent MS analysis to overcome current limitations.

Objective

Scientific studies indicate that inefficient epigenetic control is associated with a wide variety of non-communicable diseases (NCDs) like cancer, schizophrenia, and diabetes. Indeed, histone post translational modifications (PTMs) are crucial for many cellular processes including transcription and DNA repair. Thus, the ability to readily and reliably detect PTMs is crucial to better understand epigenetic processes and the complex functions of histone PTMs in human diseases. Mass spectrometry (MS) is the technique of choice to identify such modifications across the proteome. MS requires an enrichment step generally performed using antibodies, but these have several limitations such as high costs, batch-to-batch variability and data reproducibility. In a multidisciplinary effort ENRICH aims at developing new cost-effective, fast and efficient tools for the enrichment of post translationally modified proteins overcoming the current limitation. ENRICH will functionalize nanoparticles (NPs) with molecular receptors able to enrich PTM-containing peptides, derived from proteolytic digestion, for subsequent MS analysis. Concurrently, the ability and selectivity of the synthesized receptors and functionalized NPs will be evaluated via spectroscopic analyses. The ENRICH network gathers the expertise required to tackle this challenge. The consortium is composed of 9 high-level academic research groups from 2 different continents (Europe and America) and 2 highly innovative companies. By the seconding of 87 ERs/ERSs across Europe and worldwide, the aim is to capitalize on the consortium expertise in complementary fields such as chemical synthesis, spectroscopy, and proteomics. The network promotes an effective integrate training of researchers, boosting their career development, and promotes collaborations between the partners. The direct involvement of industries guarantees the timely exploitation of the results from research laboratories to innovative products.

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HORIZON-TMA-MSCA-SE - HORIZON TMA MSCA Staff Exchanges

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Call for proposal

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(opens in new window) HORIZON-MSCA-2022-SE-01

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Coordinator

UNIVERSITA DEGLI STUDI DI PARMA
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.

€ 423 200,00
Address
VIA UNIVERSITA 12
43121 PARMA
Italy

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Region
Nord-Est Emilia-Romagna Parma
Activity type
Higher or Secondary Education Establishments
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Total cost

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Participants (4)

Partners (6)

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