Project description
Transfer RNAs: a trigger for diabetes?
Chronic inflammation in obese individuals perturbs organ homeostasis and may lead to insulin resistance and type 2 diabetes (T2D). Emerging evidence indicates that macrophages play a major role in the metabolic switch that takes place prior to T2D development. The key objective of the EU-funded MATREX project is to further investigate the mechanisms responsible for macrophage activation. Researchers will focus on transfer RNAs (tRNA) known for their key role in protein translation. The rationale behind MATREX is that changes in the tRNA pool and integrity in adipose tissue and pancreatic islets may reflect metabolic changes in obesity that trigger T2D onset.
Objective
Obesity is a major public health concern and represents the strongest risk factor for type 2 diabetes (T2D) development. In T2D pathogenesis, inflammation contributes to multi-organ insulin resistance and pancreatic β-cell failure. Macrophages (Mφs) in adipose tissue and pancreatic islets play an important role in organ homeostasis, however their metabolic switch leads to chronic inflammation in obese individuals. The functional profile of obese Mφs reflects a high complexity, not explained by the classical model of pro-inflammatory activation. This suggests that unknown molecular modulators, higly sensitive to environmental changes, might control the activation of Mφs. Here I propose to investigate the role of transfer RNAs (tRNA) and tRNA fragmentation in in Mφ activation and diabetes pathogenesis. The ensemble of tRNAs in the cell is under strict regulation of nutrient availability and directly controls protein translation; also, tRNA fragmentation is controlled by stress factors and leads to the formation of tRNA fragments (tRFs), highly functional non-coding RNAs. I propose to study changes in tRNA pool and tRF signature in Mφs from adipose tissue and pancreatic islet using the db/db mouse model. I will analyse how protein translation is associated with tRNA pool, using ribosome profiling and computational methodologies. In addition, I will investigate the function of tRFs in the crosstalk between Mφs and β-cells via exosomes and their role in modulating β-cell function. I will use a Mφ-specific mouse model allowing the labeling of small RNAs in Mφs and the detection of the transferred molecules in β-cells. I will therefore combine high-throughput and in vivo innovative approaches to achieve the following aims: 1) Analyze the modulation of tRNA pool and translational in obese macrophages; 2) Investigating tRNA fragmentation and tRFs function in Mφs and β-cells during diabetes pathogenesis; 3) Study tRFs role in exosome-mediated Mφ to β-cell signaling.
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 public health
- medical and health sciences clinical medicine endocrinology diabetes
- medical and health sciences basic medicine physiology homeostasis
- medical and health sciences health sciences nutrition obesity
- natural sciences computer and information sciences artificial intelligence computational intelligence
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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-2020
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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.
1015 LAUSANNE
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.