Project description
Deciphering the role of post-translational modifications in macrophages
During inflammation, macrophages become activated by altering gene expression or modifying existing proteins through post-translational modifications such as deacetylation. Deacetylation involves the removal of acetyl groups from lysine residues in proteins and is performed by histone deacetylase enzymes such as HDAC6. The EU-funded IMMUNOACETYL project will investigate the role and mechanism by which HDAC6 regulates mitochondrial dynamics and drives anti-bacterial functions. The results will unveil novel HDAC6 targets and substrates implicated in the inflammatory response of macrophages, fuelling future research in the field. Moreover, given the involvement of mitochondrial dynamics in several cellular functions, the results may have broader implications beyond the innate immune system.
Objective
Macrophages are key cellular components of innate immunity. During inflammation, they respond to danger signals by inducing gene expression or altering pre-existing proteins. One such post-translational modification is carried out by histone deacetylases, enzymes that remove acetyl groups from lysine. HDAC6 is a unique member of this family due to its cytoplasmic localisation and its structure (two catalytic domains and one zinc finger ubiquitin binding domain). Several targets of HDAC6 have been identified, including, recently, the mitochondrial protein mitofusin1, which induces mitochondrial fusion upon its deacetylation. Mitochondrial dynamics control several cellular functions, including inflammatory and antimicrobial pathways. My exciting project is based on strong preliminary data; there is no doubt that HDAC6 regulates mitochondrial dynamics and contributes to antibacterial functions, however the exact mechanism and the importance of each HDAC6 domain remains unclear. Thus, I will identify the exact role of HDAC6 and its three domains on the mitochondrial dynamics and the immune response in general. This project will also contribute to the characterization of new HDAC6-dependent pathways and HDAC6 substrates involved in the inflammatory response, delivering potential targets for future research. This proposal is based on an ideal synergy between the host laboratory (expertise in HDAC6 and proteomic analysis) and me (expertise in macrophage, mitochondria and microscopy). Thus, this project is highly feasible and combines: 1) an in-depth investigation of the role of HDAC6 on mitochondrial dynamics and immune response as well as 2) an analysis of HDAC6-dependent metabolites and 3) an unbiased acetylome screen. This project is perfectly in line with the Horizon 2020 Programme objectives. It will enhance my competences through advanced training and mentorship, allowing me to reintegrate with the European research environment and establish my own research group.
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 chemical sciences inorganic chemistry transition metals
- natural sciences physical sciences optics microscopy
- medical and health sciences basic medicine immunology
- 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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H2020-EU.1.3. - EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions
MAIN PROGRAMME
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H2020-EU.1.3.2. - Nurturing excellence by means of cross-border and cross-sector mobility
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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.
MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF)
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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) H2020-MSCA-IF-2019
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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.
4056 Basel
Switzerland
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.