PTMtalk
Financiado
Cracking the Post Translational Modification Crosstalk Code in S. cerevisiae
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 wi...
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.
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Duración del proyecto: 62 meses
Fecha Inicio: 2024-10-15
Fecha Fin: 2029-12-31
Fecha Fin: 2029-12-31
Línea de financiación: concedida
El organismo HORIZON EUROPE notifico la concesión del proyecto el día 2024-10-15
Presupuesto
El presupuesto total del proyecto asciende a
1M€
Líder del proyecto
AGENCIA ESTATAL CONSEJO SUPERIOR DE INVESTIGA...
Investigaciones agrarias
Perfil tecnológico
TRL
2-3
552M
Perfil tecnológico
TRL
2-3
552M