Objective
The posttranslational modification of proteins with polyubiquitin regulates virtually all aspects of cell biology. This versatility arises from eight distinct linkage types between individual ubiquitin moieties in polyubiquitin, which co-exist in cells, are independently regulated, and eventually determine the fate of the modified protein. However, ubiquitin chain architecture can be highly complex, and the extent of ‘chain branching’ is unknown. Moreover, ubiquitin also undergoes phosphorylation and acetylation, which can dramatically alter its function.
A true appreciation of the complexity in the ubiquitin code can only be achieved when all above aspects are considered, and only then will it be possible to assign cellular readouts to distinct ubiquitination events and differentiate between ubiquitin signals in cells.
While the complexity of ubiquitination is daunting, work from many laboratories including my own has exemplified how basic biochemistry, a detailed understanding of mechanism and quantitative mass-spectrometry allows us to study, and eventually understand, the ubiquitin code.
In this proposal, new methods and approaches are outlined that will allow a detailed monitoring of polyubiquitin chain architectures from cellular samples (AIM 1), and also lead to an in depth understanding of additional posttranslational modifications, such as ubiquitin phosphorylation and acetylation in cells (AIM 2). Moreover, new research tools for unstudied K6- and K33-linked polyubiquitin will give insights into cellular roles for these linkage types (AIM 3). Our studies will focus on ubiquitination events on mitochondria leading to mitophagy, where unstudied K6-linked chains as well as phospho-ubiquitin are part of complex chain architectures, and mechanisms of signalling are still unclear. Our work will reveal fundamental principles in ubiquitination, and are of high medical relevance due to the links to Parkinson’s disease, infectious disease, and cancer.
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.
- medical and health sciences health sciences infectious diseases
- natural sciences biological sciences biochemistry biomolecules proteins
- natural sciences biological sciences cell biology
- medical and health sciences basic medicine neurology parkinson
- natural sciences biological sciences molecular biology structural biology
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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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H2020-EU.1.1. - EXCELLENT SCIENCE - European Research Council (ERC)
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.
ERC-COG - Consolidator Grant
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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-2016-COG
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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.
SN2 1FL SWINDON
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.