Regulation of the cGAS-STING pathway in inflammation and immune defense

Responsable de l’encadrement : Nicolas Manel

Tél : 01 56 24 64 33 E-mail:

Institut Curie

Résumé du Projet de Stage

The ability of the cells to detect and respond to non-self and altered self is essential for host defense and survival. In mammals, the cGAS-STING pathway has emerged as a crucial mediator of intracellular DNA detection and innate immune defenses. cGAS detects the presence of DNA and produces the second messenger cGAMP, which binds to the intracellular receptor STING, resulting in the activation of inflammatory signaling pathways. Activation of the cGAS-STING pathway is now recognized to play a major role in a wide range of human conditions, including infections, cancer, inflammatory diseases, and aging. Furthermore, key protein domains of cGAS and STING are conserved in evolution. cGAS-STING, therefore, represents a universal pathway of cellular defenses through life. It is therefore crucial to understand how the pathway is controlled.

Our lab has contributed to seminal studies in the cGAS-STING field, including mechanisms of intracellular viral detection (Immunity 2013, Science 2015, Science Immunology 2017, Cell 2018, Science Signaling 2021), the intracellular control of cGAS-STING (J Exp 2017, 2019, 2020), the regulation of nuclear cGAS (Cell Reports 2019, Cell 2021).

Recently, we have identified novel putative regulators of cGAS and STING through genetic and proteomic screens. These regulators have potential significance to viral infections, inflammatory diseases, cancer immunity, and aging. The M2 student will have the possibility to study a selection of these new factors, in collaboration with more senior scientists in the team.

Our lab employs all the state-of-the-art techniques in molecular biology, cellular biology, imaging, proteomics, cytometry, genomics, mouse models, and human primary cells. We are located at Institut Curie, a leading and internationally recognized research center at the heart of Paris, in a highly collaborative and multidisciplinary team and immunology department. A previous lab experience in molecular plasmid cloning is strongly desirable for this M2 project.


Lab website:

Dernières Publications en lien avec le projet :

  1. Nadia Jeremiah, Hermine Ferran, Konstantina Antoniadou, Kevin De Azevedo, Jovan Nikolic, Mathieu Maurin, Philippe Benaroch, Nicolas Manel. RELA tunes innate-like interferon I/III responses in human T cells. JEM. 2023. doi: 10.1084/jem.20220666
  2. Bakhos Jneid, Aurore Bochnakian, Caroline Hoffmann, Fabien Delisle, Emeline Djacoto, Philémon Sirven, Jordan Denizeau, Christine Sedlik, Yohan Gerber-Ferder, Frédéric Fiore, Ramazan Akyol, Carine Brousse, Robert Kramer, Ian Walters, Sylvain Carlioz, Hélène Salmon, Bernard Malissen, Marc Dalod, Eliane Piaggio, Nicolas Manel. Selective STING stimulation in dendritic cells primes anti-tumor T cell responses. Science Immunology. 2023. doi: 10.1126/sciimmunol.abn6612
  3. Guilherme P.F. Nader, Sonia Agüera-Gonzalez, Fiona Routet, Matthieu Gratia, Mathieu Maurin, Valeria Cancila, Clotilde Cadart, Andrea Palamidessi, Rodrigo Nalio Ramos, Mabel San Roman, Matteo Gentili, Ayako Yamada, Alice Williart, Catalina Lodillinsky, Emilie Lagoutte, Catherine Villard, Jean-Louis Viovy, Claudio Tripodo, Jérôme Galon, Giorgio Scita, Nicolas Manel*, Philippe Chavrier*, Matthieu Piel*. Compromised nuclear envelope integrity leads to TREX1-dependent DNA damage and tumor cell invasion. Cell. 2021. doi: 10.1016/j.cell.2021.08.035  
  4. Marius Döring, Kevin De Azevedo, Guillermo Blanco-Rodriguez, Francesca Nadalin, Takeshi Satoh, Matteo Gentili, Xavier Lahaye, Nilushi S. De Silva, Cécile Conrad, Mabel Jouve, Mireille Centlivre, Yves Lévy, and Nicolas Manel. Science Signaling. 2021. doi: 1126/scisignal.abd9720
  5. Matthieu Gratia, Mathieu Paul Rodero, Cecile Conrad, Elias Bou Samra, Mathieu Maurin, Gillian I Rice, Darragh Duffy, Patrick Revy, Florence Petit, Russell C Dale, Yanick J Crow*, Mounira Amor-Gueret*, Nicolas Manel*. Bloom syndrome protein restrains innate immune sensing of micronuclei by cGAS. The Journal of Experimental Medicine. 2019. doi: 1084/jem.20181329
  6. Matteo Gentili, Xavier Lahaye, Francesca Nadalin, Guilherme F. P. Nader, Emilia Puig Lombardi, Solène Herve, Nilushi S. De Silva, Derek C Rookhuizen, Elina Zueva, Christel Goudot, Mathieu Maurin, Aurore Bochnakian, Sebastian Amigorena, Matthieu Piel, Daniele Fachinetti, Arturo Londoño-Vallejo, Nicolas Manel. The N-terminal domain of cGAS determines preferential association with centromeric DNA and innate immune activation in the nucleus. Cell Reports. 2019. doi: 1016/j.celrep.2019.01.105
  7. Xavier Lahaye, Matteo Gentili, Aymeric Silvin, Cécile Conrad, Léa Picard, Mabel Jouve, Elina Zueva, Mathieu Maurin, Francesca Nadalin, Gavin J. Knott, Baoyu Zhao, Fenglei Du, Marlène Rio, Jeanne Amiel, Archa H. Fox, Pingwei Li, Lucie Etienne, Charles S. Bond, Laurence Colleaux, Nicolas Manel. NONO Detects the Nuclear HIV Capsid to Promote cGAS-Mediated Innate Immune Activation. Cell. 2018. doi: 1016/j.cell.2018.08.062
  8. Silvin, A., Yu, C., Lahaye, X., Imperatore, F., Brault, J., Cardinaud, S., Becker, C., Kwan, W., Conrad, C., Maurin, M., Goudot, C., Marques-Ladeira, S., Wang, Y., Pascual, V., Anguiano, E., Albrecht, R., Iannacone, M., García-Sastre, A., Goud, B., Dalod, M., Moris, A., Merad, M, Palucka, A.K.*, Manel, N.* (2017) Constitutive resistance to viral infection in human CD141+ dendritic cells. Science Immunology. 2017. doi: 1126/sciimmunol.aai8071
  9. Cerboni, N. Jeremiah, M. Gentili, U. Gehrmann, C. Conrad, MC. Stolzenberg, C. Picard, B. Neven, A. Fischer, S. Amigorena, F. Rieux-Laucat*, N. Manel*. Intrinsic anti-proliferative activity of the innate sensor STING in T lymphocytes. The Journal of Experimental Medicine. 2017. 214:1769. DOI: 10.1084/jem.20161674
  10. Matteo Gentili, Joanna Kowal, Mercedes Tkach, Takeshi Satoh, Xavier Lahaye, Cécile Conrad, Marilyn Boyron, Bérangère Lombard, Sylvère Durand, Guido Kroemer, Damarys Loew, Marc Dalod, Clotilde Théry, Nicolas Manel. Transmission of Innate Immune Signaling by Packaging of cGAMP in Viral Particles. Science. 2015, 349:1232. doi: 1126/science.aab3628
  11. Xavier Lahaye, Takeshi Satoh, Matteo Gentili, Silvia Cerboni, Cécile Conrad, Ilse Hurbain, Ahmed El Marjou, Christine Lacabaratz, Jean-Daniel Lelièvre, Nicolas Manel. The Capsids of HIV-1 and HIV-2 Determine Immune Detection of the Viral cDNA by the Innate Sensor cGAS in Dendritic Cells. Immunity. 2013, 39:1132. DOI: 10.1016/j.immuni.2013.11.002

Ce projet s’inscrit dans la perspective d’une thèse

 Ecole Doctorale de rattachement :  BioSPC ED562


Equipe d’Accueil : Immunité Innée

Intitulé de l’Unité : Immunité et Cancer

Nom du Responsable de l’Unité : Ana-Maria Lennon

Nom du Responsable de l’Équipe : Nicolas Manel

Adresse : Institut Curie, INSERM U932, 12 rue Lhomond, 75005 Paris