Project description
Investigating organelle interaction in fatty liver disease
Metabolic dysfunction-associated fatty liver disease (MAFLD) has been associated with systemic metabolic dysregulation, yet no medications are available. Given the high prevalence of the condition in the adult population, there is an urgent need to better understand the underlying mechanisms that cause MAFLD. Funded by the Marie Skłodowska-Curie Actions programme, the METACT project focuses on the interaction between cellular organelles, namely mitochondria and the endoplasmic reticulum. Researchers will study how these organelles interact with each other and how sensitive this interplay is to the cellular energy states. Project findings have the potential to unveil therapeutic targets for MAFLD treatment.
Objective
Metabolic dysfunction-associated fatty liver disease (MAFLD) is the liver manifestation of metabolic syndrome, consisting in a hepatic accumulation of lipids. While MAFLD is predicted to concern near 50% of the global adult population in 2040, no medication has been developed to counter its progression. Recent studies have identified a novel interorganelle communication in the liver, that consists in the endoplasmic reticulum engaging contact sites with both mitochondria and peroxisome, hence termed as peroxisome-endoplasmic reticulum-mitochondria (PEWM) complex. Individually, mitochondria-endoplasmic reticulum contact sites (MERCS) and peroxisome-endoplasmic reticulum contact sites (PERCS) have been described to regulate mitochondria function and peroxisome biogenesis, respectively. Although the formation of a tri-organellar complex suggests an interplay between MERCS and PERCS, this has not been evaluated yet. Recent report have shown that lipid metabolism regulation affects PEWM complexes formation. Additionally, MERCS abundance correlates with the progression of MAFLD, further suggesting a role of PEWM complexes in MAFLD pathogenesis. We will develop innovative PERCS- and MERCS-specific imaging probes to evaluate how changes in energy substrates availability affect simultaneously the formation of MERCS and PERCS. Our second objective is to deepen the understanding of PEWM complex as a regulatory hub, by questioning whether and how the modulation of MERCS and PERCS alters the function of peroxisome and mitochondria, respectively. Furthermore, we will identify the components of MERCS and PERCS that impart their metabolic sensitivity. Finally, we will evaluate in vivo how integrity of PEWM complexes is regulated throughout the progression of MAFLD. We will study animal models of PERCS deficiency to assess their interplay with MERCS and their role in MAFLD pathogenesis. This could lead to the discovery of a novel therapeutical target for treating MAFLD.
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 basic medicine pharmacology and pharmacy pharmaceutical drugs
- natural sciences biological sciences biochemistry biomolecules lipids
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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)
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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
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-2023-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.
35122 PADOVA
Italy
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.