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Defining a repertoire of innate immunity genes contributing to intracellular defense against pathogens

English title Defining a repertoire of innate immunity genes contributing to intracellular defense against pathogens
Applicant Fellay Jacques
Number 147665
Funding scheme Sinergia
Research institution Institut de Microbiologie Faculté de Biologie et Médecine CHUV/Université de Lausanne
Institution of higher education University of Lausanne - LA
Main discipline Medical Microbiology
Start/End 01.08.2013 - 31.07.2016
Approved amount 1'100'000.00
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All Disciplines (3)

Discipline
Medical Microbiology
Experimental Microbiology
Genetics

Keywords (1)

genomics, functional genomics, immunity

Lay Summary (French)

Lead
Il ya un intérêt croissant dans la compréhension des composants de la machinerie qui confère une protection aux agents pathogènes au niveau cellulaire. Le projet actuel porte sur la difficulté d'identifier les composants parmi les nombreux gènes qui contribuent à l'immunité innée.
Lay summary

La défense contre les pathogènes intracellulaires est un élément (but ?) fondamental de l'immunité innée de l'homme. Toutefois, le nombre de gènes définis comme faisant partie de l'immunité innée est grand, et il ya une nécessité d'améliorer les critères permettant d'identifier le sous-ensemble de gènes qui agissent comme effecteurs intracellulaires de première ligne. Dans ce projet de recherche, nous explorons et nous développons des outils et des approches fonctionnelles qui peuvent aider à redéfinir des sous-ensembles de l'immunité innée et à interpréter la variation de ces gènes dans le génome humain. Nous mettons l'accent sur ??l'identification des composantes de la défense contre les pathogènes intracellulaires à l'aide de l'infection à VIH comme modèle. Trois groupes de recherche convergent vers cet objectif:

1. Génomique évolutive (Evgenny Zdobnov, Université de Genève)

2. Génomique humaine (Jacques Fellay, de l'EPFL)

3. Génomique fonctionnelle (Amalio Telenti, UNIL / CHUV)

Le résultat attendu de ce projet est l’identification de signatures d'un sous-ensemble de gènes de l'immunité innée avec des capacités effectrices, leur évaluation dans des systèmes in vitro, et l'identification de variations humaines au sein de ces gènes qui pourraient avoir des conséquences sur la santé.

Direct link to Lay Summary Last update: 15.07.2013

Responsible applicant and co-applicants

Employees

Publications

Publication
Identification of Siglec-1 null individuals infected with HIV-1.
Martinez-Picado Javier, McLaren Paul J, Erkizia Itziar, Martin Maureen P, Benet Susana, Rotger Margalida, Dalmau Judith, Ouchi Dan, Wolinsky Steven M, Penugonda Sudhir, Günthard Huldrych F, Fellay Jacques, Carrington Mary, Izquierdo-Useros Nuria, Telenti Amalio (2016), Identification of Siglec-1 null individuals infected with HIV-1., in Nature communications, 7, 12412-12412.
Innate immune defects in HIV permissive cell lines.
Rausell Antonio, Muñoz Miguel, Martinez Raquel, Roger Thierry, Telenti Amalio, Ciuffi Angela (2016), Innate immune defects in HIV permissive cell lines., in Retrovirology, 13(1), 43-43.
Single-Cell Genomics for Virology.
Ciuffi Angela, Rato Sylvie, Telenti Amalio (2016), Single-Cell Genomics for Virology., in Viruses, 8(5), 00.
Evolutionary genomics and HIV restriction factors.
Pyndiah Nitisha, Telenti Amalio, Rausell Antonio (2015), Evolutionary genomics and HIV restriction factors., in Current opinion in HIV and AIDS, 10(2), 79-83.
Identification of potential HIV restriction factors by combining evolutionary genomic signatures with functional analyses.
McLaren Paul J, Gawanbacht Ali, Pyndiah Nitisha, Krapp Christian, Hotter Dominik, Kluge Silvia F, Götz Nicola, Heilmann Jessica, Mack Katharina, Sauter Daniel, Thompson Danielle, Perreaud Jérémie, Rausell Antonio, Munoz Miguel, Ciuffi Angela, Kirchhoff Frank, Telenti Amalio (2015), Identification of potential HIV restriction factors by combining evolutionary genomic signatures with functional analyses., in Retrovirology, 12, 41-41.
Identification of potential HIV restriction factors by combining evolutionary genomic signatures with functional analyses.
McLaren Paul J, Gawanbacht Ali, Pyndiah Nitisha, Krapp Christian, Hotter Dominik, Kluge Silvia F, Götz Nicola, Heilmann Jessica, Mack Katharina, Sauter Daniel, Thompson Danielle, Perreaud Jérémie, Rausell Antonio, Munoz Miguel, Ciuffi Angela, Kirchhoff Frank, Telenti Amalio (2015), Identification of potential HIV restriction factors by combining evolutionary genomic signatures with functional analyses., in Retrovirology, 12, 41-41.
Sincell: an R/Bioconductor package for statistical assessment of cell-state hierarchies from single-cell RNA-seq.
Juliá Miguel, Telenti Amalio, Rausell Antonio (2015), Sincell: an R/Bioconductor package for statistical assessment of cell-state hierarchies from single-cell RNA-seq., in Bioinformatics (Oxford, England), 31(20), 3380-2.
Analysis of stop-gain and frameshift variants in human innate immunity genes
Rausell A Mohammadi P McLaren PJ Bartha I Xenarios I Fellay J Telenti A (2014), Analysis of stop-gain and frameshift variants in human innate immunity genes, in PLoS Comp Biol, 10(7), e1003757-e1003757.
Genomics of host-pathogen interactions
Rausell A Telenti A (2014), Genomics of host-pathogen interactions, in Current Opinion in Immunology, 30C, 32-38.
GuavaH: a compendium of host genomic data in HIV biology and disease
1. Bartha I McLaren PJ Ciuffi A Fellay J Telenti A (2014), GuavaH: a compendium of host genomic data in HIV biology and disease, in Retrovirology, 15, 11-17.
The mixed blessing of interferon
Telenti A (2014), The mixed blessing of interferon, in Nature, 511(7511), 537-538.
Sincell: an R/Bioconductor package for statistical assessment of cell-state hierarchies from single-cell RNA-seq.
Juliá Miguel, Telenti Amalio, Rausell Antonio, Sincell: an R/Bioconductor package for statistical assessment of cell-state hierarchies from single-cell RNA-seq., in Bioinformatics (Oxford, England).

Scientific events

Active participation

Title Type of contribution Title of article or contribution Date Place Persons involved
Swiss Society of Microbiology (SSM) Annual meeting 2016 Talk given at a conference Single-Cell analysis approach to identify cellular biomarkers for HIV permissiveness 13.06.2016 Bern, Switzerland Rato Sylvie; Rausell Antonio;
6th Swiss Virology Meeting Talk given at a conference Identification of cellular biomarkers for HIV permissiveness using a single-cell analysis approach 02.02.2016 Thun, Switzerland Fellay Jacques; Rausell Antonio; Rato Sylvie;
7th International Workshop HIV Persistence during Therapy 2015 Talk given at a conference Single cell analysis identifies biomarkers of HIV permissiveness. 08.12.2015 Miami, United States of America Rato Sylvie; Rausell Antonio;
European AIDS Clinical Society (EACS) Conference 2015 Talk given at a conference Transcriptome approaches for single cell and latency population analyses. 20.10.2015 Barcelona, Spain Rato Sylvie; Rausell Antonio;
8th International AIDS Society (IAS) 2015 Talk given at a conference Single cell diversity: Transcriptional behavior in latency 19.07.2015 Vancouver, Canada Rato Sylvie; Rausell Antonio;
Collaboratory of AIDS Research for Eradication (CARE) 2015 Talk given at a conference Transcriptome approaches for single cell and latency population analyses 14.06.2015 San Diego, United States of America Rato Sylvie; Rausell Antonio;
Collaboratory of AIDS Research for Eradication (CARE) 2015 Poster Identification of cellular biomarkers for HIV permissiveness using a single cell approach 14.06.2015 San Diego, United States of America Rato Sylvie; Rausell Antonio;
10th conference on retroviruses and opportunistic infections (CROI) 2015 Talk given at a conference Studying heterogeneity with single cell RNA-Sequencing: Single cell analysis of HIV permissiveness 09.02.2015 Seattle, United States of America Fellay Jacques; Rausell Antonio; McLaren Paul;
American Society of Human Genetics ASHG 2014 Talk given at a conference Analysis of stop-gain and frameshift variants in human innate immunity genes 18.10.2014 San Diego, United States of America Rausell Antonio; Fellay Jacques; McLaren Paul;
International Society for Computational Biology ISMB 2014 Poster Analysis of stop-gain and frameshift variants in human innate immunity genes 15.07.2014 Boston, United States of America Rausell Antonio;


Associated projects

Number Title Start Funding scheme
149724 Novel mechanisms of HIV control in the infected cell 01.12.2013 Project funding
132863 Host evolutionary genomics of HIV-1 and other retroviruses 01.11.2010 Project funding

Abstract

Intracellular defense against pathogens is a fundamental component of human innate immunity. However, the numbers of genes defined as being part of innate immunity is large, and there is a need for better criteria to identify the subset of genes acting as intracellular effectors. In this proposal we explore and advance tools and functional approaches that can assist re-defining subsets of innate immunity and interpreting variation in the human genome. We place emphasis on the identification of components of the intracellular defense against pathogens using HIV infection as a model. Three research groups converge on this goal:1. Evolutionary genomics (Zdobnov laboratory)?Identification of evolutionary signatures that characterize different sets of genes of the innate immunity.?Identification of non-annotated genes that share the characteristics of specific subsets of genes of the innate immunity.2. Human genomics (Fellay laboratory)?Accessing population-level human genome sequence data and cataloguing genetic variation.?Identification of genomic signatures that characterize different sets of genes of the innate immunity.?Assessment of impact of variation in innate immunity genes on infection phenotypes in human patient populations3. Functional genomics (Telenti laboratory)?Development of the concept of permissive cells (HIV model) as a tool for the identification of effector genes.?Single cell analysis to identify the basis of cell-to-cell heterogeneity in permissiveness.The expected outcome of the project is the generation of signatures of a subset of genes of the innate immunity with effector capacities, their testing in in vitro systems, and the identification of human variation within these genes with possible phenotypic consequences.
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