Membrane Dynamics & Viruses

Our team « Membrane Dynamics & Viruses » (MDV) aims at studying virus-host interactions at different spatiotemporal scales. The viruses studied in the lab allow us to better understand physiological molecular and cellular mechanisms, and vice-versa, the investigation of cellular processes provides valuable information regarding viral subversion mechanisms.
Specifically, our projects are focusing on three complementary axes:
  1. The intracellular transport in/out: how do the hepatitis B and C viruses (HBV and HCV respectively) interact with their receptor at the cell surface of target cell? Conversely, how does the cell control neo-synthesized transmembrane viral receptor secretion and extracellular vesicles?
  2. Manipulate intracellular trafficking to better understand viruses and cells: deep characterization of the mode of action of a broad-spectrum antiviral molecule that interfere with the endolysosomal trafficking pathway.
  3. Impact of viral infections on cellular functions through the induction of subcellular rearrangement: how does HIV and Zika virus influence circulating monocytes transmigration toward tissues?

In project I, we have recently identified that DNAseI is encapsidated into viral particles during HBV assembly (Hallez et al., Nature Microbiol, 2019) and imaged the association of Core-DNAseI in real time (Figure 1).

Figure 1. 5D reconstruction of the spatiotemporal dynamics of HBV-Core (green) and DNAseI (red).

As part of project III, we found that Zika virus and HIV enhance monocyte transmigration through the blood-brain barrier in vitro and in vivo. Our results reinforce the "Trojan Horse" hypothesis (Figure 2).

 
 

Figure 2. Viral particles in the bloodstream infect (or are captured by) blood cells, which will transmigrate through the endothelium, allowing the virus to cross this impermeable barrier.

We are routinely employing techniques related to the study of HBV, HCV, HIV, and Zika viruses, including RT-qPCR, Western blot, flow cytometry, immunostaining, RNA interference, plaque assays, …
We also developed advanced methods for the study of virus-host interactions such as CRISPR/Cas9 knock-in/out, RUSH, high resolution 3D confocal live cell imaging, mass spectrometry, xenotypic zebrafish embryo model system, …

The philosophy of the lab is to go beyond technological limitations, not accepting “we can’t do it” as an answer, but rather “how are we going to achieve it?”.


Funding

Ongoing:
  • Atip-Avenir, ANRS, INSERM-région, ANR.

Past (since 2016) :

  • FRM, EMBO LTF, chaire d’attractivité Idex (University of Strasbourg), Prestige (european), initiation of collaboration with China (franco-chinese ambassy).

Current team members


From upper left to lower right : Nilda Vanesa Ayala-Nunez, Camille Clément, Raphael Gaudin, Emma Partiot, Maika Deffieu

Past team members

Eliott Vernier, Student Master 1 BIOTIN Montpellier - Today: Master 2 BIOTIN
Cristina Dorobantu, Post-doc (EMBO LTF) – Today: Project manager at ViroClinics, Rotterdam (The Netherlands)
Vincent Lucansky, Research engineer (FRM) – Today: Staff scientist at Biomedical Center Martin JFM CU (Slovakia)
Ieva Cesonyte, ESBS engineer school student – Today: PhD student in Dr. van Kuppeveld lab, Utrecht (The Netherlands)
Lucie Klughertz, Master 2 student in Virology
Laurine Seltz, ESBS engineer school student



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Sept 2019

the "Spicy challenge", organised by Vanesa: a lot of fun!




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Aug 2019

We can't say who it is just yet, but it seems that a new member is going to join the team in Jan 2020; and it will happen despite the Brexit...



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Aug 2019

New review written by Maika and Raphael about live cell imaging of the hepatitis B virus just published in Trends Microbiol. Congrats!


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July 2019

The lab has (finally) its own twitter account: for more news about the team's activities and scientific interests, follow us: @Gaudinlab


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May 2019

Lab day: Axe throwing in Castelnau-le-Lez. No one was hurt!


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Apr 2019

We are happy to welcome Emma Patiot in our team, starting April 1st, 2019. Emma will work in collaboration with all the team members and initiate her own PhD project in September.



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Dec 2018

Our recently published work has been highlighted in the last issue of the Inserm magazine :






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Nov 2018

Congratulations to Vanesa who won the 1st prize for best oral presentation at the SoMM 2018 meeting!




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Nov 2018

We are happy to welcome Eliott Vernier, student from the Master 1 BIOTIN of Montpellier. He will work with Vanesa and Raphael to develop innovative technologies (Crispr, microfluidics, ...).



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Oct 2018

The MDV team started in Alsace in 2016. We moved to Montpellier on October 1st, 2018. After heavy unpacking and heavy rain episods, we are back to the lab, ready to move forward our research projects at IRIM, in an exciting and stimulating environment.


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Karting day, Feb 2018




Pubmed list from Raphael Gaudin

https://www.ncbi.nlm.nih.gov/pubmed/?term=raphael+gaudin

Published papers since 2015 :

* Co-first authors
# Co-corresponding authors

  1. Deffieu MS & Gaudin R#. Imaging the Hepatitis B Virus: Broadcasting Live. Trends in Microbiology. 2019 Aug 14. pii: S0966-842X(19)30191-X. doi: 10.1016/j.tim.2019.07.007.

  2. Pascolutti R, Algisi V, Conte A, Raimondi A, Pasham M, Upadhyayula S, Gaudin R, Maritzen T, Barbieri E, Caldieri G, Tordonato C, Confalonieri S, Freddi S, Malabarba MG, Maspero E, Polo S, Tacchetti C, Haucke V, Kirchhausen T, Di Fiore PP, Sigismund S. Molecularly Distinct Clathrin-Coated Pits Differentially Impact EGFR Fate and Signaling. Cell Reports. 2019 Jun 4;27(10):3049-3061.e6. doi: 10.1016/j.celrep.2019.05.017.

  3. Hallez C, Li X, Suspène R, Thiers V, Bouzidi1 MS, Dorobantu C, Lucansky V, Wain-Hobson S, Gaudin R#, Vartanian JP#. Hypoxia induced human deoxyribonuclease I is a cellular restriction factor of hepatitis B virus. Nature Microbiology. 2019 Apr 1. doi: 10.1038/s41564-019-0405-x.

  4. Théry C, Witwer KW, …, Gaudin R, … (> 300 authors). Minimal information for studies of extracellular vesicles 2018 (MISEV2018): a position statement of the International Society for Extracellular Vesicles and update of the MISEV2014 guidelines. Journal of Extracellular Vesicles. 2018 Nov 23;7(1):1535750. doi: 10.1080/20013078.2018.1535750.

  5. Padilla-Rodriguez M, Parker SS, Adams DG, Westerling T, Puleo JI, Watson AW, Hill SM, Noon M, Gaudin R, Aaron J, Tong D, Roe DJ, Knudsen B, Mouneimne G. The actin cytoskeletal architecture of estrogen receptor positive breast cancer cells suppresses invasion. Nature Communication. 2018 Jul 30;9(1):2980. doi: 10.1038/s41467-018-05367-2.

  6. Coulter ME*, Dorobantu CM*, Lodewijk GA*, Delalande F, Cianferani S, Ganesh VS, Smith RS, Lim ET, Xu CS, Pang S, Wong ET, Lidov HGW, Calicchio ML, Yang E, Gonzalez DM, Schlaeger TM, Mochida GH, Hess H, Lee WA, Lehtinen MK, Kirchhausen T, Haussler D, Jacobs FMJ#, Gaudin R#, Walsh CA#. The ESCRT-III Protein CHMP1A Mediates Secretion of Sonic Hedgehog on a Distinctive Subtype of Extracellular Vesicles. Cell Reports. 2018 Jul 24;24(4):973-986.e8. doi: 10.1016/j.celrep.2018.06.100.

  7. Faure F, Jouve M, Lebhar-Peguillet I, Sadaka C, Sepulveda F, Lantz O, Berre S, Gaudin R, Sánchez-Ramón S, Amigorena S. Blood monocytes sample MelanA/MART1 antigen for long-lasting cross-presentation to CD8+ T cells after differentiation into dendritic cells. International Journal of Cancer. 2018 Jan 1;142(1):133-144. doi: 10.1002/ijc.31037.

  8. He K, Marsland R, Upadhyayula S, Song E, Dang S, Capraro BR, Wang W, Skillern W, Gaudin R, Ma M and Kirchhausen T. Dynamics of phosphoinositide conversion in clathrin-mediated endocytic traffic. Nature. 2017 Dec 13. doi: 10.1038/nature25146. Highlighted in F1000Prime.

  9. Chou YY, Krupp A, Kaynor C, Gaudin R, Ma M, Cahir-McFarland E, Kirchhausen T. Inhibition of JCPyV infection mediated by targeted viral genome editing using CRISPR/Cas9. Scientific Reports. 2016 Nov 14;6:36921. doi: 10.1038/srep36921.

  10. Aguet F*, Upadhyayula S*, Gaudin R*, Chou YY, Cocucci E, He K, Chen BC, Mosaliganti K, Pasham M, Skillern W, Legant WR, Liu TL, Findlay G, Marino E, Danuser G, Megason S, Betzig E, Kirchhausen T. Membrane dynamics of dividing cells imaged by lattice light-sheet microscopy. Molecular Biology of the Cell. 2016 Nov 7;27(22):3418-3435. Highlighted.

  11. Verrier ER, Colpitts CC, Bach C, Heydmann L, Zona L, Xiao F, Thumann C, Crouchet E, Gaudin R, Sureau C, Cosset FL, McKeating JA, Pessaux P, Hoshida Y, Schuster C, Zeisel MB, Baumert TF. Solute Carrier NTCP Regulates Innate Antiviral Immune Responses Targeting Hepatitis C Virus Infection of Hepatocytes. Cell Reports. 2016 Oct 25;17(5):1357-1368. doi: 10.1016/ j.celrep.2016.09.084.

  12. Chou YY, Cuevas C, Carocci M, Stubbs SH, Ma M, Cureton DK, Chao L, Evesson F, He K, Yang P, Whelan SP, Ross SR, Kirchhausen T#, Gaudin R#. Identification and characterization of a novel broad spectrum virus entry inhibitor. Journal of Virology. Feb 2016. pii: JVI.00103-16.

  13. Gaudin R. [Enhancing our single molecule experience using Crispr]. Médecine/Sciences. Nov 2015 31(11):959-61. doi: 10.1051/medsci/20153111007. Highlighted.

  14. Gaudin R# and Barteneva NS#. Sorting of small infectious virus particles by flow virometry reveals distinct infectivity profiles. Nature Communications. Feb 2015 2;6:6022. doi: 10.1038/ncomms7022.
  • Sarah Cianferani, Christine Carapito, François Delalande and Aurélie Hirschler - LSMBO, Strasbourg
  • Alain Wagner and Guilhem Chaubet – BFC team, Illkirch-Graffenstaden
  • Jacky Goetz and Gautier Follain - INSERM U1109, Strasbourg
  • Pascal Thérond, Institute de Biologie Valrose (IBV), University of Nice, France
  • Nolwenn Jouvenet - Institut Pasteur, Paris
  • Sherif Zaki and Gillian Hale - Center for disease control (CDC), Atlanta, USA
  • Jean Pierre Vartanian - Institut Pasteur, Paris
  • Yves Mély - Faculté de Pharmacie, Illkirch-Graffenstaden
  • Franck Perez and Gaelle Boncompain - Institut Curie, Paris
  • Tao Xu and Eli Song - Institute of Biophysics, Chinese Academy of Science, Beiging, China
  • Chris Walsh and Mike Coulter - Harvard Medical School et HHMI, Boston, USA
  • Ghassan Mouneimne – The University of Arizona Cancer Center, Tucson, USA
We are always looking for motivated students interested in our work.


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On Nov 19th, 2018. EXPIRED



Post-doc position in EV biology

Study of the secretion of a novel subpopulation of extracellular vesicles

We are looking for a motivated post-doctoral scientist to join the research team “Membrane dynamics & viruses” (MDV) headed by Raphael Gaudin, part of the IRIM UMR9004 - CNRS research institute, Montpellier, France. Our lab is interested in various aspects of intracellular trafficking pathways in health and disease. In particular, we are currently studying secretion of biological entities out of the cells, including extracellular vesicles and viruses. We recently discovered a novel extracellular vesicle subtype containing Sonic Hedgehog (Shh) we called ART-EVs (Coulter, Dorobantu et al. Cell Rep, 2018) and we aim to better characterize these vesicles and their secretory route. The proposed project will take advantage of state-of-the-art imaging techniques, Crispr-Cas9 strategies and other innovative approaches mastered in the lab.

Key words: Exosomes; Extracellular vesicles; Intracellular trafficking; Membrane dynamics; Secretion

Profile and skills of the candidate: You are going to defend or already hold a PhD in Cell biology with experience in membrane trafficking. Previous experience with exosomes or extracellular vesicles is a plus. You are curious, motivated and have a problem-solving mindset. The successful candidate is expected to perform bench work and communicate his/her results through internal and external seminars. The project will be conducted in collaboration with two other labs with in vivo and proteomics expertise. The applicant is expected to speak English, while French is not a prerequisite.

Lab: The institute is located on the CNRS campus of Montpellier in the sunny south of France. We offer an internationally renowned research environment with direct access to modern infrastructures and advanced facilities for imaging and flow cytometry.

Dead line / Starting dates: Mid 2019    

Team leader


Raphaël Gaudin

MDV team leader, CRCN CNRS, HDR



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At a glance

The MDV team studies what viruses do to cells... Or what cells do to viruses... Well, we study the intimate virus-cell relationship

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Funding












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Contact us


     
   

   

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IRIM
Institut de Recherche en Infectiologie de Montpellier
UMR 9004 - CNRS / UM
1919 route de Mende - 34293 Montpellier cedex 5
FRANCE

 

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