Project description
Deciphering the post-translational modification crosstalk in S. cerevisiae
Post-translational modifications (PTMs) are chemical changes that regulate protein functionality. PTMs crosstalk with each other, sending signals that influence one another in regulating cellular adaptation, while the deregulation of crosstalk is often linked to disease. Understanding the complexities of crosstalk could provide answers to the cause and treatment of certain diseases. The ERC-funded PTMtalk project aims to develop a systematic method to study the function of PTM crosstalk and its regulation in S. cerevisiae (baker’s yeast). It will combine advanced CRISPR-based editing methods to construct 30 000 PTM-mutants in all the proteins involved in the signalling-to-chromatin pathways and a scalable systems biology approach based on reverse genetics and chemical genomics to profile these mutants under 150 stress conditions.
Objective
Post-translational modifications (PTMs) regulate all aspects of protein functionality. Dysregulation of PTMs or the enzymes that regulate them is frequently associated with disease. Far from working in isolation, PTMs crosstalk with each other creating decision-making circuits that regulate the cellular adaptation to fluctuating environments. PTM crosstalk is a regulatory layer of the proteome across the tree of life. However, to what extent and how PTM crosstalk regulates biological processes is a long-standing question in biology that is experimentally challenging to tackle. The challenges lie in the natural complexity and infinite combinatorial possibilities of PTMs, and the lack of unbiased systematic methods to study their function.
We will use a combination of state-of-the-art CRISPR-based editing methods to construct 30.000 PTM-mutants in all the proteins involved in the signalling-to-chromatin pathways, and a scalable systems biology approach based on reverse genetics and chemical genomics to profile these mutants under 150 stress conditions. Mutants with similar phenotypic profiles are functionally associated, allowing us to infer functional relationships for PTMs, regulators and conditions. These functional associations will provide conditional regulatory PTM crosstalk events at an unprecedented scale. We will further mechanistically dissect the function of selected PTM crosstalk events by interrogating protein activity, cellular localization and interactions. Moreover, we will dissect their directionality and modularity. We expect these findings to be transferable to other eukaryotes due to the high degree of conservation in these core biological processes. Overall, this project will revolutionise the PTM field providing ground-breaking insights into the functional understanding of PTM crosstalk and their regulation in S. cerevisiae and unlocking the door for cracking the PTM code within and across biological processes.
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
- natural sciences biological sciences biochemistry biomolecules proteins proteomics
- natural sciences biological sciences biochemistry biomolecules proteins enzymes
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Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Programme(s)
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Multi-annual funding programmes that define the EU’s priorities for research and innovation.
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HORIZON.1.1 - European Research Council (ERC)
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(opens in new window) ERC-2024-STG
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28006 Madrid
Spain
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