Membrane Dynamics & Viruses

Last minute: given the current covid-19 pandemic, our lab refocuses researches to develop antivirals against SARS-CoV-2 (Project II below). Thank you to the team members, and Maika Deffieu in particular, for their help to optimise protocols for production and detection of the virus (plaque assays, RT-qPCR, flow cytometry and microscopy). Thank you to CNRS (INSB) for their financial support.

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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?”.


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The team is affiliated to the French society for cell biology (SBCF) and R.Gaudin is an elected member of the SBCF board council since 2016


R.Gaudin has been nominated as "full member" of the World Society for Virology (WSV) in 2019.



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

Past team members

Hafida Boultam, Master 2 student
Nilda Vanesa Ayala-Nunez, Post-doc
Camille Clément, PhD student
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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Oct 2020
Two newcomers this month:
Diana Brychka (left), 1-year engineer, will pursue our work on HIV and transmigration.
Vincent Lucansky (right), 3-months visiting scientist from Slovakia, will develop projects based on new molecular biology tools.

 

     





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May 2020
Release of two scientific review from the lab the same week! Congrats to Emma and Vanesa for their drafting work.

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May 2020
William Bakhache, a ready-to-defend PhD student from Laurence Briant team (IRIM) is recruited as an engineer (SATT AxlR of Montpellier) to develop antiviral projects through a mini-consortium at IRIM coordinated by Raphael Gaudin and including te groups of Laurence Briant, Caroline Goujon and Jean-Marie Péloponèse.

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Mar 2020
The institute closes down as France is entering in lock-down. The team, Maika and Raph, followed by Yonis, stay at the bench to further develop broad spectrum antivirals showing potent activity against SARS-CoV-2.

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Feb 2020
Lab outing: Bowling -> I don't have pictures, sorry!

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Jan 2020

Despite an imminent Brexit coming up, Yonis Bare, whom has just defended his thesis at King's College London, joins our team as post-doctoral fellow. He will study extracellular vesicle secretion, and maybe even some HIV...!

Welcome




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Dec 2019

Happy ending: Camille Clément defended her thesis on Dec 16th 2019, despite the strike that firced us to have to reviewers by videoconference. Anyway, everything ends well and Camille is today proud to be called Dr. Clément. Congratulations!!!


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Oct 2019

It's official: Emma Partiot is starting her PhD in the MDV team! Let's go for 3 years of transmigration!




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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 :

Bold: team members
* Co-first authors
# Corresponding authors


  1. [Monocytes and Zika virus: the brain's conquest]. Partiot E & Gaudin R#. Medecine/Sciences (Paris). 2020 May;36(5):449-451. doi: 10.1051/medsci/2020072. Epub 2020 May 26.
  2. A viral journey to the brain: Current considerations and future developments.
    Ayala-Nunez NV & Gaudin R#. PLoS Pathogens. 2020 May 21;16(5):e1008434. doi: 10.1371/journal.ppat.1008434.
  3. Characterisation of endogenous Claudin-1 expression, motility and susceptibility to hepatitis C virus in CRISPR knock-in cells. Clément CMH*, Deffieu MS*, Dorobantu CM, Baumert TF, Ayala-Nunez NV, Mély Y, Ronde P, Gaudin R#. Biology of the Cell. 2020 Feb 7. doi: 10.1111/boc.201900085.

  4. Dynamics of Auxilin 1 and GAK in clathrin-mediated traffic. He K, Song E, Upadhyayula S, Dang S, Gaudin R, Skillern W, Bu K, Capraro BR, Rapoport I, Kusters I, Ma M, Kirchhausen T. Journal of Cell Biology. 2020 Mar 2;219(3). pii: e201908142. doi: 10.1083/jcb.201908142.

  5. Zika virus enhances monocyte adhesion and transmigration favoring viral dissemination to neural cells. Ayala-Nunez NV, Follain G, Delalande F, Hirschler A, Partiot E, Hale GL, Bollweg BC, Roels J, Chazal M, Bakoa F, Carocci M, Bourdoulous S, Faklaris O, Zaki SR, Eckly A, Uring-Lambert B, Doussau F, Cianferani S, Carapito C, Jacobs FMJ, Jouvenet N, Goetz JG, Gaudin R#. Nature Communications. 2019 Sep 27;10(1):4430.
    doi: 10.1038/s41467-019-12408-x.

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

  7. Molecularly Distinct Clathrin-Coated Pits Differentially Impact EGFR Fate and Signaling. 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. Cell Reports. 2019 Jun 4;27(10):3049-3061.e6. doi: 10.1016/j.celrep.2019.05.017.

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

  9. 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. Théry C, Witwer KW, …, Gaudin R, … (> 300 authors). Journal of Extracellular Vesicles. 2018 Nov 23;7(1):1535750. doi: 10.1080/20013078.2018.1535750.

  10. The actin cytoskeletal architecture of estrogen receptor positive breast cancer cells suppresses invasion. 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. Nature Communication. 2018 Jul 30;9(1):2980. doi: 10.1038/s41467-018-05367-2.

  11. The ESCRT-III Protein CHMP1A Mediates Secretion of Sonic Hedgehog on a Distinctive Subtype of Extracellular Vesicles. 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#. Cell Reports. 2018 Jul 24;24(4):973-986.e8. doi: 10.1016/j.celrep.2018.06.100.

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

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

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

  15. Membrane dynamics of dividing cells imaged by lattice light-sheet microscopy. 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. Molecular Biology of the Cell. 2016 Nov 7;27(22):3418-3435. Highlighted.

  16. Solute Carrier NTCP Regulates Innate Antiviral Immune Responses Targeting Hepatitis C Virus Infection of Hepatocytes. 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. Cell Reports. 2016 Oct 25;17(5):1357-1368. doi: 10.1016/ j.celrep.2016.09.084.

  17. Identification and characterization of a novel broad spectrum virus entry inhibitor. 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#. Journal of Virology. Feb 2016. pii: JVI.00103-16.

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

  19. Sorting of small infectious virus particles by flow virometry reveals distinct infectivity profiles. Gaudin R# and Barteneva NS#. Nature Communications. Feb 2015 2;6:6022. doi: 10.1038/ncomms7022.
  • Sarah Cianferani, Christine Carapito, François Delalande & Aurélie Hirschler - LSMBO, Strasbourg
  • Jacky Goetz - INSERM U1109, Strasbourg
  • Pascal Thérond, Institut de Biologie Valrose (IBV), Université de Nice, France
  • Nolwenn Jouvenet - Institut Pasteur, Paris
  • Franck Perez & Gaelle Boncompain - Institut Curie, Paris
  • Grégory Lavieu - Institut Curie, Paris
  • Pablo Vargas - Institut Curie, Paris
  • Benoit Charlot - IES, Montpellier
  • Orestis Faklaris - MRI, Montpellier
  • Ganesh Gowrishankar - LIRMM, Montpellier
  • Frank Jacobs - University of Amsterdam, The Netherlands
  • Eli Song - Institute of Biophysics, Chinese Academy of Science, Beiging, China
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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