Project description
Scientists revealing new blueprints for post-translational modifications in proteins
After transcription of DNA to RNA, the RNA is used to translate the code into proteins with the help of ribosomes. Many proteins undergo post-translational modifications (PTMs) that can occur at any time throughout the life cycle of a protein. There are currently a couple of hundred different types of known PTMs, and they are key players in protein diversity. While the human genome has about 20 000 to 25 000 genes, the human proteome has more than a million different proteins. The ambitious EU-funded nbPTMs project is on a discovery mission to reveal as-yet-unknown nucleotide-based post-translational modifications and to map them throughout eukaryotic proteomes. Cataloguing new chemical substrates of modifications, their locations and the types of modifications they undergo provides the starting point from which to investigate their roles in health and disease.
Objective
Nucleotide-based post-translational modifications (nbPTMs) play key roles in health and disease, from bacterial pathogenesis to cancer. However, technical challenges of these versatile, but chemically complex protein modifications have constrained our fundamental understanding of even the most intensely studied nbPTMs for decades. The overarching aim of this proposal is to establish, apply and disseminate a methodology to unveil novel types of nbPTMs and allow site-specific proteomic analyses. The conceptual innovation lies in a strategy for turning the complex chemical structures of nbPTMs from a challenge to an advantage. First, shared chemical moieties will be exploited to develop pan-specific enrichment of multiple nbPTMs. For this purpose, we will generate the first nbPTMs-specific antibodies by converting specific signalling proteins into biotechnology tools for chemoenzymatic synthesis of challenging peptide antigens (aim 1). Second, we will take advantage of the chemical lability of nbPTMs to analyse modified peptides using a nucleobase-targeted mass spectrometry approach (aim 2). The unbiased scope of our methodology will make possible the discovery of as yet unknown forms of nbPTMs (aim 3) and nbPTM site mapping throughout eukaryotic proteomes (aim 4). These new materials, methods, discoveries and datasets will be made publicly available to allow future investigations of nbPTMs by the scientific community. The new substrates, sites and nbPTMs will provide starting points for biological characterization (aim 5). Poised at the interface of biology and technology, this interdisciplinary research project has the potential to explore new territories within established biomedical fields and to contribute to the knowledge base for improved treatment of diseases.
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 biochemistry biomolecules proteins proteomics
- medical and health sciences clinical medicine oncology
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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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H2020-EU.1.1. - EXCELLENT SCIENCE - European Research Council (ERC)
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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
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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.
ERC-COG - Consolidator Grant
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Call for proposal
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
(opens in new window) ERC-2019-COG
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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.
80539 MUNCHEN
Germany
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