Objective
Work conducted in my laboratory on the trypanosome killing factor of human serum led to the identification
of the primate-specific Apolipoprotein L1 (APOL1) as a novel pore-forming protein with striking similarities
with proteins of the apoptotic BCL2 family. APOL1 belongs to a family of proteins induced under
inflammatory conditions in myeloid and endothelial cells. APOL1 is efficiently neutralized by the SRA
protein of Trypanosoma rhodesiense, accounting for the ability of this trypanosome subspecies to infect
humans and cause sleeping sickness. We found that natural APOL1 variants escaping SRA neutralization and
therefore conferring human resistance to T. rhodesiense are associated with chronic kidney disease.
Moreover, transgenic mice expressing these APOL1 variants exhibit an obese phenotype. Our unpublished
results also indicate that APOLs control the lifespan of dendritic cells and podocytes activated by viral
stimuli. Therefore, we propose that the pathology of APOL variants is due to their deregulated activity on the
control of the cellular lifespan in myeloid/endothelial cells activated by pathogen detection.
This project aims at characterizing (i) the molecular mechanism by which APOLs control the lifespan of
activated dendritic cells and podocytes, which has direct impact on innate immunity and inflammation, and
(ii) the mechanism by which APOL1 variants cause pathology. In addition, we plan to detail the
physiological function of APOLs by studying the phenotype of transgenic mice either expressing human
APOL1 (wild-type and variants) or devoid of APOL genes, which we have recently generated. Finally, we
propose to exploit the extraordinary potential of trypanosomes for antigenic variation in order to produce
SRA variants able to neutralize the pathogenic APOL1 variants. Preliminary experiments suggest that in
podocytes SRA antagonizes APOL1 induction by viral stimulus and subsequent cell death, opening new
perspectives to treat kidney disease.
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: https://op.europa.eu/en/web/eu-vocabularies/euroscivoc.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: https://op.europa.eu/en/web/eu-vocabularies/euroscivoc.
- medical and health sciences clinical medicine psychiatry sleep disorders
- natural sciences biological sciences biochemistry biomolecules proteins
- medical and health sciences basic medicine immunology
- medical and health sciences basic medicine pathology
- medical and health sciences clinical medicine nephrology kidney diseases
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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.1.1. - EXCELLENT SCIENCE - European Research Council (ERC)
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.
ERC-ADG - Advanced Grant
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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) ERC-2014-ADG
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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.
1050 Bruxelles / Brussel
Belgium
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.