Project description
Profiling C-switch proteins and their potential in novel therapies
Some proteins can temporarily transition between two conformations, acting as molecular on-off switches controlling cellular processes. The purine nucleotides GTP and ATP are well-established cofactors, molecules required for this switching. In 2019, the pyrimidine nucleotide CTP was added to this cofactor list. Very few studies have been done on the ‘C-switches’ that depend on CTP for activation although they are likely highly diverse and widespread. Building on their 2019 discovery, the ERC-funded C-SWITCH project aims to use bioinformatic, in vitro and in vivo studies to identify and characterise new types of C-switch proteins. They appear to be absent in humans and could be targets for antibacterial and antiviral therapies.
Objective
Nucleotide-dependent molecular switches play key roles in the regulation of cellular processes such as translation, protein folding and transport, cytoskeletal dynamics and cell differentiation. Until recently, their function was thought to rely exclusively on the purine nucleotides GTP or ATP as cofactors. This paradigm changed in 2019, when my group identified a fundamentally new class of regulatory switches, now called C-switches, that depend on the pyrimidine nucleotide CTP.
The few C-switches studied to date have important functions in bacterial growth and pathogenicity. Database searches predict that C-switches are highly diverse and widespread in nature. However, the physiological roles and modes of action of these proteins are still largely enigmatic. The overarching goal of C SWITCH is to provide comprehensive insight into the biology of C-switches and clarify the ways in which this newly identified regulatory principle can control protein activity and cellular functions. For this purpose, we will employ both bioinformatic and experimental methods to systematically identify new types of C-switch proteins and perform detailed mechanistic studies of prototypic representatives, using state-of-the-art in vitro and in vivo approaches. C-SWITCH will thus break new ground in the understanding of cellular regulation and pave the way to a global understanding of C-switches as versatile regulators in biology. Importantly, proteins containing a canonical C-switch domain are absent from humans and other mammalian systems. C-SWITCH will therefore also explore the pharmacological potential of C-switches as new targets for antibacterial and antivirulence therapies, thereby possibly opening new avenues for translational applications and supporting the current global effort to combat bacterial antibiotic resistance.
Fields of science (EuroSciVoc)
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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 computer and information sciences databases
- natural sciences biological sciences biochemistry biomolecules proteins
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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.1.1 - European Research Council (ERC)
MAIN PROGRAMME
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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.
HORIZON-ERC - HORIZON ERC Grants
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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-2022-ADG
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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.
35037 Marburg
Germany
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