Cellular biologist with an emphasis in cell cytoskeleton and host-pathogen interactions
INSERM senior research associate (CR) since October 2012.
Institute of Pharmacology and Structural biology (IPBS), UMR 5089, CNRS-University of Toulouse, France.
PI in the group of Dr. I. Maridonneau-Parini
I received my PhD in cell biology from Toulouse University in 2007. My dissertation work in the M. Wright and then A. Merdes lab was funded, in part, by the Pierre Fabre laboratories and dealt with the characterization of protein complexes involved in microtubules organization during mitosis, in Drosophila (Verollet et al, J Cell Biol, 2006 & 2009). My keen interest in cell cytoskeleton organization led me to join the I. Maridonneau-Parini lab at IPBS, where I conducted work in the characterization of HIV-1 infection of macrophages in terms of fusion into multinucleated giant cells (MGC) and cell migration (Verollet et al, J Immunol, 2010). In particular, we showed that HIV-1 infection of macrophages and infected MGC display high motility in 3D matrices, favoring virus dissemination (Verollet et al, Blood, 2015). In parallel, I worked on osteoclasts biology, showing the role of Hck in osteoclast migration and bone degradation (Verollet et al, Faseb J, 2013). This postdoctoral fellowships (2008-12) were sponsored by ANRS and Sidaction awards. In 2012, I was recruited as a permanent researcher by INSERM. As such, I investigate the role of macrophages in HIV-1 pathogenesis and HIV-1/Mtb co-infection (Souriant et al., Cell Reports, 2019; Dupont et al., Elife, 2020; Mascarau et al., IJMS, 2020) as well as the biology of osteoclasts in physiological and pathological contexts (Raynaud-Messina et al., PNAS, 2018). In December 2018, I received my HDR (Habilitation à Diriger de Recherches) diploma from Paul Sabatier University.
Mechanisms of osteoclast formation
Staff: Ophélie Dufrançais (PhD student), Brigitte Raynaud-Messina & Christel Vérollet
Collaborations: Christophe Thibault and Laurent Malaquin (LAAS, Toulouse, France)
Fundings: Young investigator ANR (2016-2019) & University Paul Sabatier (PhD fellowship -Inspire project)
The aim of this project is to study the cellular and molecular mechanisms of osteoclast formation. Osteoclasts are multinucleated cells of myeloid origin responsible for the degradation of bone. We will develop innovative approaches to study the fusion of osteoclastic precursors, in particular using a microfluicic system called "Pairing". We will study the role of protein candidates in osteoclast fusion but also the cellular structures involved (i.e. podosomes & Tunneling NanoTubes-TNT) and the consequences on bone resorption. We thus hope to identify new players in fusion/function of human osteoclasts and to validate the role of these molecules in vivo in mice. Finally, the effect of age on osteoclast fusion will be addressed using monocytes from elderly donors (humans) or aging mouse models. The potential modifications of identified proteins during aging will be studied.
Mechanisms of cell-to-cell transfer of HIV-1 toward macrophages
Staff: Remi Mascarau (PhD student), Brigitte Raynaud-Messina & Christel Vérollet
Collaboration: Serge Benichou, Cochin Institute
Fundings: ANRS 2018-2021
Macrophages are cellular targets of HIV-1 that play crucial roles in the physiopathology of infection as well as in virus dissemination and establishment of persistent virus reservoirs in numerous host tissues. Virus cell-to-cell transmission and dissemination involve the different cell types targeted by HIV-1, including myeloid cells, and are suspected to be major determinants for virus dissemination in vivo. Our collaborator revealed a fast and efficient viral transfer from infected T-lymphocytes to macrophages through a cell fusion process. Here, the aim is to understand, both at the structural and molecular levels, the mechanisms involved in cell-to-cell transfer of HIV-1 for efficient infection of macrophages from infected T lymphocytes. We want to i/ analyze the architecture of the initial cell contacts between HIV-1-infected T lymphocytes and macrophages, ii/ study the molecular mechanisms involved in virus cell-to-cell transfer and dissemination in macrophages and iii/ characterize this process ex vivo with human tissue macrophages from chirurgical explants. We hypothesize that F-actin cytoskeleton and in particular proteins associated to podosomes could localize in macrophages at the site of contact with infected T cells, and could regulate both this contact and the efficiency of the cell-to-cell fusion process.
How do Mycobaterium Tuberculosis exacerbate HIV-1 infection of macrophages?
Staff: Shanti Souriant (PhD, Oct 2017), Maeva Dupont (PhD, Dec 2019) & Christel Vérollet
Collaborations at IPBS: Geanncarlo Lugo-Villarino, Yoann Rombouts & Olivier Neyrolles
Collaborations: Luciana Balboa (CONICET, LIA CNRS, Buenos Aires, Argentina)
Fundings: ANRS (2015-2017 & 2020-2023), ECOS Sud Argentine, LIA CNRS
Co-infection with Mycobacterium tuberculosis (Mtb), the etiological agent of tuberculosis (TB), and HIV-1 is major health issue in the world. The synergistic relationship between HIV-1 and Mtb is known to result in increased pathogen proliferation and associated pathogenesis, worsening diagnosis and treatment. The central tenet of our project is that M. tuberculosis exacerbates HIV-1 infection in human macrophages through important changes in their activation and functional program. We intend to identify and characterize host signaling and cellular pathways modulated by M. tuberculosis favoring cell-to-cell transmission of HIV-1. In particular, we focus now on the role of TNT in pathogen spread during co-infection (Souriant et al., Cell Reports, 2018; for review, see Dupont et al., Frontiers Immunol., 2018). We recently uncover a deleterious role for the Siglec-1/CD169 lectin in TB-HIV-1 co-infection (Dupont et al., eLIFE, 2020); and Siglec-1 localization on TNT opens new avenues to understand cell-to-cell viral spread.
2020 ANRS, Project leader. Project : Cellular and molecular mechanisms involved in tuberculosis-mediated exacerbation of HIV-1 infection in macrophages: focus on Siglec-1 and tunneling nanotubes
2016 ANR "Young Investigator" grant. Project : MechanOCs
My scientific achievements consist in 18 original research articles and 8 literature reviews, accumulating around 700 citations with an h-index of 15, according to Google scholar.
Most relevant publications
• Dupont M, …, Neyrolles O*, Maridonneau-Parini I*, Vérollet C*,#, Lugo-Villarino G*,#. Tuberculosis-associated IFN-I induces Siglec-1 on tunneling nanotubes and favors HIV-1 spread in macrophages. Elife, 2020 Mar 30;9.
• Souriant S, …, Neyrolles O*, Maridonneau-Parini I*, Lugo-Villarino G*,#, Vérollet C*,#. Tuberculosis exacerbates HIV-1 infection through IL-10/STAT3-dependent tunneling nanotube formation in macrophages. Cell Reports, 2019 Mar 26.
• Raynaud-Messina B#, Bracq L, Dupont M, Souriant S, Usmani SM, Proag A, Pingris K, Soldan V, Thibault C, Capilla F, Al Saati T, Gennero I, Jurdic P, Jolicoeur P, Davignon JL, Mempel TR, Benichou S, Maridonneau-Parini I*, Vérollet C*,#. Bone degradation machinery of osteoclast: An HIV-1 target that contributes to bone loss. Proc Natl Acad Sci U S A, 2018 Feb 20.
• C. Vérollet, S. Souriant, E. Bonnaud, P. Jolicoeur, B. Raynaud-Messina, C. Kinnaer, I. Fourqaux, A. Ilme, S. Benichou, O. Fackler, R. Poincloux and I. Maridonneau-Parini. HIV-1 reprograms the migration of macrophages. Blood, 2015, Mar 5;125(10):1611-22.
• C. Vérollet, YM. Zhang, V. Le Cabec, J. Mazzolini, GM. Charrière, A. Labrousse, J. Bouchet, I. Medina, E. Biessen, F. Niedergang, S. Benichou and I. Maridonneau-Parini. HIV-1 Nef triggers macrophage fusion in a p61Hck and protease dependent manner. J. Immunol., 2010 June;184(12):7030-9.
• A. Bouissou*, C. Vérollet*, A. Sousa, P. Sampaio, M. Wright, A. Merdes and B. Raynaud-Messina. Novel role of g-Tubulin Ring Complexes as microtubule plus-end stabilizing factors in Drosophila cells. J. Cell. Biol, 2009 Nov;187(3): 335. Novel role of γ-TuRC in microtubule dynamics.
• C. Vérollet, N. Colombié, T. Daubon, H-M. Bourbon, M. Wright and B. Raynaud-Messina. Drosophila γ-TuRC is dispensable for targeting γ-tubulin to the centrosome and microtubule nucleation. J. Cell. Biol. 2006 Feb;172(4). First description of the role of γ-TuRC in mitosis.
* co-authors; # corresponding author
5 PhD students, more than 10 Master students and 3 visiting/foreign students.
Expert referee in scientific journals, & Associate, Review and Topic Editor for Frontiers in Immunology.
Member of the Scientific Committee at École Doctorale Biologie-Santé-Biotechnologies (N°151 Biologie/Santé), Toulouse
Director of the BSL3 facility at IPBS.