Our team is interested in understanding and analyzing the interactions of pathogens with their host, leading to its infection and possible destruction. Our targets of interest are diverse and include type 6 and type 9 secretion systems, and the host immune response with a particular focus on the role of antibodies.
Understanding host-pathogen interactions is at the heart of the fight against pathogens involved in infectious diseases (viruses, bacteria).
For about ten years, we have been studying the structure and adhesion mechanism of bacteriophages (viruses infecting bacteria) infecting the bacterium used in the milk industry, Lactococcus lactis. We have determined the structures of several phage virions by electron microscopy, and that of the anti-receptors or baseplate (sets of 1-2 Mda), eventually complexed to their receptor, by X-ray diffraction. Still in the field of virology, we have recently launched a project on the human hepatitis E virus (HEV).
With regard to bacterial infections, we have tackled the study of bacterial secretory systems, in particular those of type VI (T6SS) and type 9 (T9SS). We have determined the structure and interactions of some of the 13 components of T6SS. We aim to reconstruct the entire system using a “hybrid” approach including electron microscopy and X-ray diffraction. The same approach is applied to T9SS.
The studies we conduct focus on one hand on factors of pathogenicity of bacteria and on the other hand on means of response of host organisms. Our projects can be grouped in 2 scientific disciplines which are immunology and microbiology.
At the methodological level, X-ray crystallography will remain the basis of all our studies but we are aware of the current developments in the field of structural biology. In particular, the rise of electron microscopy is opening up new avenues. We are also running a camelid antibody generation platform (also called VHH or Nanobody). This tool gives us a significant competitive advantage in tackling most of our projects.
Type IX Secretion System (T9SS)
C. elegans innate immunity
This project, in collaboration with Jonathan Ewbank (CIML, Marseille), aims at deciphering the host-pathogen relationships between C. elegans and the obligate fungal pathogen Drechmeria coniospora. By RNAi screening on whole C. elegans genome, our collaborators identified 270 genes involved in the nematode innate immunity. Among them, only 33 have no functional annotation, and even fewer are specific to nematodes and are not present in other metazoans. On the other hand, virulence factors from D. coniospora were identified and those not present in other fungi and without functional annotation were selected. Our objective is to solve the structures of the nematode and D. coniospora specific proteins; functional studies are carried out in parallel by our collaborators.
Thi Thu Hang Le, Christine Kellenberger, Marie Boyer, Pierre Santucci, Nicolas Flaugnatti, Eric Cascales, Alain Roussel, Stéphane Canaan, Laure Journet, Christian Cambillau
International Journal of Molecular Sciences 24:1740 (2023)10.3390/ijms24021740
Olivier Fuchsbauer, Ignacio Lunar Silva, Eric Cascales, Alain Roussel, Philippe Leone
Journal of Biological Chemistry 298:101618 (2022)10.1016/j.jbc.2022.101618
Adeline Goulet, Christian Cambillau, Alain Roussel, Isabelle Imbert
Viruses 14 (2022)10.3390/v14071537
Quentin Pagneux, Alain Roussel, Hiba Saada, Christian Cambillau, Béatrice Amigues, Vincent Delauzun, Ilka Engelmann, Enagnon Kazali Alidjinou, Judith Ogiez, Anne Sophie Rolland, Julien Poissy, Alain Duhamel, Rabah Boukherroub, David Devos, Sabine Szunerits
Communications Medicine 2:56 (2022)10.1038/s43856-022-00113-8
van Son Nguyen, Silvia Spinelli, E. Cascales, Alain Roussel, Christian Cambillau, Philippe Leone
PLoS ONE 16:e0254232 (2021)10.1371/journal.pone.0254232
Olivier Fuchsbauer, Paolo Swuec, Claire Zimberger, Beatrice Amigues, Sébastien Levesque, Daniel Agudelo, Alexis Duringer, Antonio Chaves-Sanjuan, Silvia Spinelli, Geneviève Rousseau, Minja Velimirovic, Martino Bolognesi, Alain Roussel, Christian Cambillau, Sylvain Moineau, Yannick Doyon, Adeline Goulet
Molecular Cell 76:922-937.e7 (2019)10.1016/j.molcel.2019.09.012
Philippe Leone, Jennifer Roche, Maxence S Vincent, Quang Hieu Tran, Aline Desmyter, E. Cascales, Christine Kellenberger, Christian Cambillau, Alain Roussel
Nature Communications 9 (2018)10.1038/s41467-017-02784-7
van Son Nguyen, Badreddine Douzi, Eric Durand, Alain Roussel, E. Cascales, Christian Cambillau
Current Opinion in Structural Biology 49:77-84 (2018)10.1016/j.sbi.2018.01.007
Badreddine Douzi, Nhung Trinh, Sandra Michel-Souzy, Aline Desmyter, Genevieve Ball, Pascale Barbier, Artemis Kosta, Eric Durand, Katrina Forest, Christian Cambillau, Alain Roussel, Romé Voulhoux
mBio 8 (2017)10.1128/mBio.01185-17
van Son Nguyen, Laureen Logger, Silvia Spinelli, Pierre Legrand, Thi Thanh Huyen Pham, Thi Trang Nhung Trinh, Yassine Cherrak, Abdelrahim Zoued, Aline Desmyter, Eric Durand, Alain Roussel, Christine Kellenberger, E. Cascales, Christian Cambillau
Nature Microbiology 2:17103 (2017)10.1038/nmicrobiol.2017.103
Maxence S Vincent, Mickaël J Canestrari, Philippe Leone, Julien Stathopulos, Bérengère Ize, Abdelrahim Zoued, Christian Cambillau, Christine Kellenberger, Alain Roussel, E. Cascales
Journal of Biological Chemistry 292:3252-3261 (2017)10.1074/jbc.M116.765081
Abdelrahim Zoued, Eric Durand, Yoann G Santin, Laure Journet, Alain Roussel, Christian Cambillau, E. Cascales
BioEssays 39 (2017)10.1002/bies.201600262
Nicolas Flaugnatti, Thi Thu Hang Le, Stéphane Canaan, Marie-Stéphanie Aschtgen, Vân Nguyên, Stephanie Blangy, Christine Kellenberger, Alain Roussel, Christian Cambillau, E. Cascales, Laure Journet
Molecular Microbiology 99:1099-1118 (2016)10.1111/mmi.13292
Eric Durand, van Son Nguyen, Abdelrahim Zoued, Laureen Logger, Gerard Pehau-Arnaudet, Marie-Stéphanie Aschtgen, Silvia Spinelli, Aline Desmyter, Benjamin Bardiaux, Annick Dujeancourt, Alain Roussel, Christian Cambillau, E. Cascales, Rémi Fronzes
Nature 523:555-560 (2015)10.1038/nature14667
van Son Nguyen, Laureen Logger, Silvia Spinelli, Aline Desmyter, Thi Thu Hang Le, Christine Kellenberger, Badreddine Douzi, Eric Durand, Alain Roussel, E. Cascales, Christian Cambillau
PLoS ONE 10:1-14 (2015)
van Son Nguyen, Silvia Spinelli, Aline Desmyter, Thi Thu Hang Le, Christine Kellenberger, E. Cascales, Christian Cambillau, Alain Roussel
Acta crystallographica Section F : Structural biology communications [2014-...] 71:266-271 (2015)10.1107/S2053230X15000709
Julien Stathopulos, Christian Cambillau, E. Cascales, Alain Roussel, Philippe Leone
Acta crystallographica Section F : Structural biology communications [2014-...] 71:71-74 (2015)10.1107/S2053230X1402559X
Badreddine Douzi, Silvia Spinelli, Stéphanie Blangy, Alain Roussel, Eric Durand, Yannick R Brunet, E. Cascales, Christian Cambillau
PLoS ONE 9:e86918 (2014)10.1371/journal.pone.0086918