Project description
A novel approach for treating malaria
Ferroptosis is a newly discovered process of iron-dependent cell death that seems to be implicated in various diseases including malaria. Scientists of the EU-funded RIGM project are working under the hypothesis that the modulation of iron metabolism could serve as a novel therapeutic intervention against malaria. Research efforts will focus on the investigation of ferroptosis in the kidneys during malaria and its impact on glucose metabolism. Transcriptomic and metabolomic analyses in a mouse model of the disease are expected to unveil novel targets of ferroptosis manipulation and help scientists understand how iron metabolism affects organ homeostasis.
Objective
Disease tolerance is pivotal for host survival in malaria. In particular, Heme/iron metabolism in parenchymal tissues, such as liver, kidney, implicates in tissue damage and metabolic reprogram during infection diseases including malaria and sepsis, etc. Therefore, heme/iron metabolism is potential target for disease tolerance modulation in treating malaria and sepsis. In support of this notion, the host lab previously found that Ho-1 and ferritin heavy chain in the kidney are important in mice fighting against malaria. Meanwhile, the underlying mechanism of heme/iron affecting organ metabolism and host homeostasis is not well understood. Studies indicated that ferroptosis cascade involves in heme/iron-driven tissue damage and other metabolic alterations. Accordingly, we intend to address the interface of ferroptosis and glucose metabolism in kidney during malaria. Malaria iwill be applied to iron exporter, Ferroportin (Slc40a1) deletion specific in renal proximal tubule epithelial cells(RPTEC) (Slc40a1 PepckΔ/Δ ). Basic disease trajectory phenotype and ferroptosis parameters will be collected to demonstrate the impact of RPTEC iron export on kidney injury and systematic homeostatic status during malaria. Based on our preliminary data, Slc40a1 PepckΔ/Δ mice are sensitive to malaria due to disease tolerance collapse which displays as lethal hypoglycaemia and temperature drop. We propose to manipulate ferroptosis cascade to ameliorate tissue damage and re-establish disease tolerance in Slc40a1 PepckΔ/Δ mice. Furthermore, we aim to investigate to interface between ferroptosis cascade and glucose metabolism. Not only will a pivotal role of renal glucose production fine-tuned by heme/iron metabolism be uncovered. Transcriptome and metabolomics will be employed to identify novel pathway/metabolites that tackle both ferroptosis and glucose metabolism. The future potency of this study, is to provide therapeutic target in treating malaria.
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 malaria
- medical and health sciences basic medicine physiology homeostasis
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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-EF-ST - Standard EF
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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.
1067-001 LISBOA
Portugal
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.