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APOLs SIGNED

Role of Apolipoproteins L in immunity and disease

Total Cost €

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EC-Contrib. €

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Partnership

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 APOLs 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.

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Project "APOLs" data sheet

The following table provides information about the project.

Coordinator
UNIVERSITE LIBRE DE BRUXELLES 

Organization address
address: AVENUE FRANKLIN ROOSEVELT 50
city: BRUXELLES
postcode: 1050
website: www.ulb.ac.be

contact info
title: n.a.
name: n.a.
surname: n.a.
function: n.a.
email: n.a.
telephone: n.a.
fax: n.a.

 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.

# participants  country  role  EC contrib. [€] 
1    UNIVERSITE LIBRE DE BRUXELLES BE (BRUXELLES) coordinator 2˙250˙000.00

Map

 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 Our unpublished results also indicate that APOLs control the lifespan of dendritic cells and podocytes activated by viral stimuli.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
List of publications.
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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