Institute of Pharmacology and Structural Biology (CNRS-University of Toulouse).
The Department of Tuberculosis and Infection Biology.
The Tuberculosis and Infection Biology (TBIB) Department is internationally recognized for its expertise in tuberculosis and research in mycobacterial diseases. It is involved in a number of projects for TB drug and vaccine development (e.g. EU Framework Programs 6, 7 and H2020, Gates grand Challenge). The Department has a staff of 70, including scientists, research assistants as well as national and international students and post-doctoral fellows.
The main objectives of the TBIB Department at IPBS are to: i) decipher the molecular mechanisms of mycobacterial pathogenicity, from the identification of microbial virulence genes to the characterization of the host response to infection, and ii) contribute to the fight against mycobacterial diseases through the identification of potential drug targets and inhibitors of these targets, and through the development of new vaccine candidates, more effective than the currently used BCG. In addition, emerging research areas of the TBIB Department deal with TB co-infection agents, such as HIV, and other pulmonary pathogens.
Our expertise ranges from the structural analysis of the microbial and host cell proteins and lipids, including the production of recombinant proteins, enzymology, genetics and structural biochemistry, to cellular biology, molecular microbiology, and antimicrobial immunology. We employ state-of-the-art technologies available in the various technological platforms (e.g. mass spectrometry, NMR, confocal and multi-photon microscopy, flow cytometry) localized at IPBS and neighboring laboratories. Importantly, the TBIB Department is a member of the Equipment of Excellence (EquipEx) project Aninfimip funded by the French government “Investments for the future” program, which allowed us to acquire state-of-the art imaging and flow cytometry equipment for our brand-new BSL2 and BLS3 animal facility.
Read more about the TBIB Department at IPBS.
The main principal scientists involved in the TBVAC2020 project are:
Dr Martine Gilleron
Senior scientist, Martine Gilleron did a PhD in biochemistry at the Toulouse University where she focused on the structural characterization of mycobacterial species-specific glycolipids. She next developed a specific expertise in NMR analysis of glycans after a post-doctoral training in Johannes F.G. Vliegenthart’s group (Utrecht University, The Netherlands). Her research, in Dr J. Nigou’s laboratory, aims at elucidating the molecular mechanisms underlying the presentation of mycobacterial (glyco)lipid antigens by CD1 molecules to T cells. Within the previous European programs, Dr M. Gilleron and Dr G. Puzo, in collaboration with European immunologists, discovered new mycobacterial lipid antigens and characterized the role of the CD1e protein in the processing of glycolipid antigens. Within TBVAC2020, Martine Gilleron and colleagues wish to identify the highly immunogenic glycolipid epitopes presented by CD1b protein on antigen presenting cells infected with Mtb.
Read more about the Nigou laboratory.
Dr Christophe Guilhot
Principal Investigator and former Head of the TBIB Department. Christophe Guilhot did a PhD in microbiology at the Pasteur Institute, Paris. He performed a post-doctoral training in Pr J. Beckwith’s laboratory at Harvard Medical School. He gained his strong expertise in mycobacterial genetics during almost 25 years in the tuberculosis research field, where he had important impact, in Brigitte Gicquel’s laboratory at the Pasteur Institute, on the development of genetic tools to engineer mycobacteria and pioneered the work on the role of lipids in mycobacterial pathogenicity. The work of his laboratory at IPBS is focused on the biogenesis of mycobacterial cell envelope, the contribution of lipids in host pathogen interaction and the persistence and transmission of mycobacterial pathogens. Within TBVAC2020, Christophe Guilhot and his team are involved in a genetic-based screening approach to identify novel live attenuated vaccine against tuberculosis.
Read more about the Guilhot laboratory.
Dr Olivier Neyrolles
Principal Investigator and Deputy Director of IPBS. Olivier Neyrolles did a PhD in microbiology at the Pasteur Institute, Paris. His experience in mycobacterial research goes back to his post-doctoral training in Douglas Young’s laboratory at Imperial College, London, and in Brigitte Gicquel’s laboratory at the Pasteur Institute, where he studied cell biology and immunology of mycobacterial infections. His laboratory at IPBS, launched in 2008, is interested in various aspects of host-pathogen interactions in TB and in HIV-TB co-infection. Within TBVAC2020, Olivier Neyrolles and colleagues of his team, Pr Denis Hudrisier, Pr Claude Gutierrez and Pr Yannick Poquet, are involved in the development of novel strategies, including live and vector-based vaccines, against tuberculosis.
Read more about the Neyrolles laboratory.
Dr Jérôme Nigou
Principal Investigator and Head of the TBIB Department. Jérôme Nigou did a PhD in biochemistry at the Toulouse University. He performed a post-doctoral training in Pr Gurdyal S. Besra’s laboratory at the University of Newcastle upon Tune, UK. He developed a strong expertise in the biosynthesis and structural and functional characterizations of mycobacterial lipoglycans. His laboratory at IPBS is interested in the role and structure-function relationships of lipids and glycoconjugates in the modulation of immune response to Mtb. Within TBVAC2020, Jérôme Nigou and colleagues are involved, in collaboration with Dr A. Peixoto, in the development of novel vaccine strategies against tuberculosis based on nanoparticles.
Read more about the Nigou laboratory.
Dr Antonio Peixoto
Scientific Head of the Bio-imaging Core Facility at IPBS. Antonio Peixoto did a PhD in Immunology of Vaccination and Infection at the Institute Necker, INSERM U591 under the supervision of Benedita Rocha. Later, A. Peixoto joined the laboratory of Ulrich von Andrian at the Harvard Medical School to study the dynamics of T cell response using Intravital Multiphoton approaches. Currently, A. Peixoto and his team are developing live imaging approaches to study in vivo immune response to lung pathogens and designing new nanoparticle based delivery systems for Mycobacterium tuberculosis antigens in order to offer the next generation of TB vaccines.
Read more about the Bio-imaging facility at IPBS.
Dr Isabelle Vergne
Senior scientist in Jérôme Nigou’s laboratory. Isabelle Vergne received her PhD in Biophysics in 1998 at the Toulouse University, France. She spent several years in the laboratory of Dr. V. Deretic (USA) as a post-doctoral fellow, then as a Research Assistant Professor, working on phagosome maturation and autophagy in the context of tuberculosis and HIV infection. She joined the IPBS in 2011 to pursue her research on deciphering the molecular cross-talk between mycobacteria and host defense mechanisms including autophagy. Within TBVAC2020, Isabelle Vergne collaborates with Dr O. Neyrolles and colleagues in the development of novel live vaccines against tuberculosis.
Read more about the Nigou laboratory.
Selected relevant publications
- Gilleron M, Lepore M, Layre E, Cala-De Paepe D, Mebarek N, Shayman JA, Canaan S, Mori L, Carrière F, Puzo G, De Libero G. Lysosomal Lipases PLRP2 and LPLA2 Process Mycobacterial Multi-acylated Lipids and Generate T Cell Stimulatory Antigens. Cell Chem Biol. 2016 Sep 22;23(9):1147-56.
- Lastrucci C et al. Tuberculosis is associated with expansion of a motile, permissive and immunomodulatory CD16(+) monocyte population via the IL-10/STAT3 axis. Cell Res 2015 doi: 10.1038/cr.2015.123.
- Brodin P et al. High content phenotypic cell-based visual screen identifies Mycobacterium tuberculosis acyltrehalose-containing glycolipids involved in phagosome remodeling. PLoS Pathog 2010 6(9):e1001100.
- Tanne A et al. A murine DC-SIGN homologue contributes to early host defense against Mycobacterium tuberculosis. J Exp Med 2009 206(10):2205-20.
- De la Salle H et al. Assistance of microbial glycolipid antigen processing by CD1e. Science 2005 310:1321-1324.
- Espert L et al. Autophagy in Mycobacterium tuberculosis and HIV infections. Front Cell Infect Microbiol 2015 2;5:49.
- Vergne et al. Manipulation of the endocytic pathway and phagocyte functions by Mycobacterium tuberculosis lipoarabinomannan. Front Cell Infect Microbiol 2015 4:187.
- Blattes E et al. Mannodendrimers prevent acute lung inflammation by inhibiting neutrophil recruitment. PNAS 2013 110(22): 8795-800.
- Liu CF et al. Bacterial protein-O-mannosylating enzyme is crucial for virulence of Mycobacterium tuberculosis. PNAS 2013 110(16): 6560-5.
- Layre E et al. Mycolic acids are scaffolds for mycobacterial lipidic antigens stimulating CD1b-restricted T cells. Chem Biol 2009 16: 82-92.
- Cala-De Paepe D et al. Deciphering the role of CD1e in mycobacterial phosphatidyl-myo-inositol-mannosides (PIM) processing for presentation by CD1b to T lymphocytes. J Biol Chem 2012 287, 31494-502.
- Gonzalo-Asensio J et al. Evolutionary history of tuberculosis shaped by conserved mutations in the PhoPR virulence regulator. PNAS. 2014 111:11491-11496.
- Leblanc C et al. 4’-Phosphopantetheinyl transferase PptT, a new drug target required for Mycobacterium tuberculosis growth and persistence in vivo. PLOS Pathog 2012 8:e1003097.
- Tabouret et al. Mycobacterium leprae phenolglycolipid-1 expressed by engineered M. bovis BCG modulates early interaction with human phagocytes. PLOS Pathog 2010 6:e1001159.