Objective
Phosphorylation has been considered as a fundamental on/off switch for protein function. However, many proteins harbour multiple phosphorylation sites arranged in dense clusters whose modification status is not reported in proteomic datasets due to technical limitations. Thus, multisite phosphorylation of dense clusters represents the dark matter of the phosphoproteome, since the very basic descriptors of function, regulation, and biology remain poorly understood. The presence of many target sites next to each other, ranging from 10 to as many as 30, raises new mechanistic questions with regard to the order of phosphorylation, or lack thereof.
DarkPhospho aims to elucidate the mechanisms and functional implications of multiphosphorylation using a panel of CK1 enzymes and their substrates – components of the Wnt pathway – as a model system and experimental toolkit. The project will take a multidisciplinary approach, comprising: (1) biophysical analysis of CK1 multiphosphorylation using nuclear magnetic resonance (NMR) and mass spectrometry (MS); (2) global kinetic analyses (computational numerical modelling) describing the stochastic nature of multiphosphorylation; and (3) role of multiphosphorylation in the regulation of protein phase separation (confocal microscopy) and Wnt signal transduction (dual luciferase reporter assay).
This project challenges the view that stochasticity at the molecular level is simply noise. The main scientific outcome will be a unified framework to analyse the diverse data and elucidate the harnessing of stochasticity in multiphosphorylation. The multidisciplinary design of the project offers the fellow extensive opportunities to diversify his research skills through training, gain valuable inter-sectoral experience, and extend his collaborative network, in line with his professional development needs and career objectives towards academic tenure.
Fields of science (EuroSciVoc)
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Keywords
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
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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HORIZON.4.1 - Widening participation and spreading excellence
MAIN PROGRAMME
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Topic(s)
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.
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
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.
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.
HORIZON-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European Fellowships
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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) HORIZON-WIDERA-2025-TALENTS-01
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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.
601 77 Brno
Czechia
The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.