Project description
Metabolite-driven regulation of the ubiquitin system
The ubiquitin system is a fundamental cellular mechanism that tags proteins for degradation, trafficking or functional modification. This process is orchestrated by approximately 650 specialised enzymes known as E3 ligases, whose activity must be tightly regulated. Aberrant ubiquitination is a hallmark of cancer and neurodegeneration. However, it remains largely unexplored how intracellular metabolites influence E3 ligase activity. With the support of the Marie Skłodowska-Curie Actions programme, the urTREAM project aims to study this metabolite-E3 ligase interaction using a multidisciplinary approach. The project will provide fundamental mechanistic insight into ubiquitin regulation and could potentially uncover novel therapeutic targets.
Objective
The ubiquitin system, a central regulator of cellular processes, relies on the activity of approximately 650 E3 ligases to mediate the ubiquitination of cellular entities. This activity is tightly regulated to avoid aberrant ubiquitination, a hallmark of numerous diseases. While several regulatory layers of ligase activity have been documented, a novel factor – activity control by metabolites – remains vastly underexplored. A key bottleneck for uncovering metabolite-driven regulation has been the lack of appropriate tools for activity read-out of cellular ligases. However, in the past few years, innovative activity-based probes have been added to our toolbox.
In this proposal, I will exploit complementary E2~Ub-mimicking probes to monitor the proteome-wide activity of both transthiolating and single subunit RING E3 ligases after manipulation of intracellular metabolite pools. By coupling mass-spectrometry-aided ligase-agnostic profiling with biophysical characterisation of the interaction, I will chart the metabolite E3 landscape, deepen our mechanistic understanding of ubiquitin regulation, and uncover new therapeutic entry points for diseases such as cancer and neurodegeneration.
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 neurobiology
- medical and health sciences clinical medicine oncology
You need to log in or register to use this function
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.
-
HORIZON.1.2 - Marie Skłodowska-Curie Actions (MSCA)
MAIN PROGRAMME
See all projects funded under this programme
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
See all projects funded under this funding scheme
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-MSCA-2025-PF
See all projects funded under this callCoordinator
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.
DD1 4HN Dundee
United Kingdom
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.