APOLs SIGNED
Role of Apolipoproteins L in immunity and disease
Total Cost €
0EC-Contrib. €
0Partnership
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0APOLs project word cloud
Explore the words cloud of the APOLs project. It provides you a very rough idea of what is the project "APOLs" about.
Project "APOLs" data sheet
The following table provides information about the project.
| Coordinator |
UNIVERSITE LIBRE DE BRUXELLES
Organization address contact info |
| Coordinator Country | Belgium [BE] |
| Total cost | 2˙250˙000 € |
| EC max contribution | 2˙250˙000 € (100%) |
| Programme |
1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC)) |
| Code Call | ERC-2014-ADG |
| Funding Scheme | ERC-ADG |
| Starting year | 2015 |
| Duration (year-month-day) | from 2015-09-01 to 2021-06-30 |
Partnership
Take a look of project's partnership.
| # | ||||
|---|---|---|---|---|
| 1 | UNIVERSITE LIBRE DE BRUXELLES | BE (BRUXELLES) | coordinator | 2˙250˙000.00 |
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Project 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 Our unpublished results also indicate that APOLs control the lifespan of dendritic cells and podocytes activated by viral stimuli.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.
Publications
| year | authors and title | journal | last update |
|---|---|---|---|
| 2016 |
Bart Cuypers, Laurence Lecordier, Conor J. Meehan, Frederik Van den Broeck, Hideo Imamura, Philippe Büscher, Jean-Claude Dujardin, Kris Laukens, Achim Schnaufer, Caroline Dewar, Michael Lewis, Oliver Balmer, Thomas Azurago, Sardick Kyei-Faried, Sally-Ann Ohene, Boateng Duah, Prince Homiah, Ebenezer Kofi Mensah, Francis Anleah, Jose Ramon Franco, Etienne Pays, Stijn Deborggraeve Apolipoprotein L1 Variant Associated with Increased Susceptibility to Trypanosome Infection published pages: , ISSN: 2150-7511, DOI: 10.1128/mBio.02198-15 |
mBio 7/2 | 2020-04-01 |
| 2017 |
Frédéric Fontaine, Laurence Lecordier, Gilles Vanwalleghem, Pierrick Uzureau, Nick Van Reet, Martina Fontaine, Patricia Tebabi, Benoit Vanhollebeke, Philippe Büscher, David Pérez-Morga, Etienne Pays APOLs with low pH dependence can kill all African trypanosomes published pages: 1500-1506, ISSN: 2058-5276, DOI: 10.1038/s41564-017-0034-1 |
Nature Microbiology 2/11 | 2020-03-03 |
| 2017 |
Gilles Vanwalleghem, Yannick Morias, Alain Beschin, David E. Szymkowski, Etienne Pays Trypanosoma brucei growth control by TNF in mammalian host is independent of the soluble form of the cytokine published pages: , ISSN: 2045-2322, DOI: 10.1038/s41598-017-06496-2 |
Scientific Reports 7/1 | 2020-03-03 |
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