Objective
Intricate networks of post-translational modifications (PTMs) shape how cells respond to environmental threats. Adenosine diphosphate (ADP)-ribosylation (ADPr) has emerged as a pivotal PTM elicited by DNA damage or host immune responses to combat viruses, including SARS-CoV-2. This protective ADPr signature can be regulated by PARP14, a versatile enzyme that can both install and remove ADPr. While the connection between ADPr signalling and these damaging events is clear, the physiological targets and functions of PARP14-mediated ADPr remain ill-defined. Recently, a cryptic link between PARP14 ADPr and ubiquitylation signalling has arisen, adding complexity to PARP14-regulated processes. This ambitious research program ‘UbADPrLINK’ aims to dissect the mechanistic underpinnings of PARP14 ADPr and its link with ubiquitylation using an integrative approach, merging proteomics, structural, biochemical methods.
UbADPrLINK will focus on four areas. First, we will precisely map and characterise cellular PARP14-catalysed ADPr sites on important targets by reconstituting ADPr in vitro. Concurrently, we will study the structure-function relationships of PARP14 and explore the roles of uncharacterised PARP14 domains and auto-modification in regulating its activity. Next, we will attempt to decipher the interplay between PARP14 and the PARP9-DTX3L complex that is known to regulate PARP14 activity using unclear mechanisms. We will structurally characterise the PARP14-PARP9-DTX3L complex and assess its potential to simultaneously modify targets with ADPr and ubiquitin. Finally, we will launch a drug discovery campaign to discover cyclic peptides capable of modulating SARS-CoV-2 by targeting PARP14 and SARS-CoV-2 domains involved in ADPr during infection.
By seeking to unravel the molecular details of PARP14-catalysed ADPr, UbADPrLINK has the potential to advance our understanding of ADPr signalling beyond the state-of-the-art and may contribute to the development of new therapies.
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 biochemistry biomolecules proteins proteomics
- natural sciences biological sciences microbiology virology
- natural sciences biological sciences genetics DNA
- medical and health sciences health sciences infectious diseases RNA viruses coronaviruses
- natural sciences biological sciences biochemistry biomolecules proteins enzymes
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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.1.2 - Marie Skłodowska-Curie Actions (MSCA)
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-MSCA-2024-PF-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.
OX1 2JD Oxford
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.