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Novembre 2018

Mardi 06/11/2018

10H00

Amphi Pasteur

“ Roles of the small RNA pathway during host-bacteria interaction : Shigella hijacks Argonaute 2 function ”

 

Dr Didier FILOPON (Institut de Biologie de l’ENS, Equipe Lionel Navarro, Paris - France)

contact : mathias.faure@inserm.fr

MicroRNAs (miRNAs) have emerged as critical fine-tuners of host immune responses in both plants and mammals. However, their functional relevance in antibacterial defense is still poorly understood. Furthermore, unlike in plants, there is no evidence of the implication of human miRNA pathway in the control of host-pathogen interactions. We used a cellular infection model with the bacterium Shigella flexneri to study the localization and functional relevance of human Argonaute 2 (Ago2) during host-bacterial interactions. Combining bio-informatics and in vitro screens we also explore a bacterial effector repertoire to identify suppressor of miRNA pathway. Altogether, our data demonstrate for the first time a critical role of Ago2, and of the human miRNA pathway, in host-bacterial interactions and suggest that pathogens target this pathway for efficient infection.

Vendredi 09/11/2018

11H00

Salle de SdT CRC

« Understanding mammalian iron-sulfur cluster assembly and the pathophysiology of Friedreich ataxia  »

 

 

Hélène PUCCIO (IGBMC) 

Contact : Bertrand Mollereau

 

Lundi 12/11/2018

11H00

Salle Condorcet

« Remodeling neural circuits in time and space »

 

Darren WILLIAMS (King’s College, London)

host: Jon Enriquez

 

Mardi 13/11/2018

11H00

Amphi pasteur
“ Regulation of Cytosolic DNA induced type I Interferon production by deubiquitination ”

 

 

 

Pr Ping WANG (School of Medicine, Tongji University, Shanghai, China)

contact : benedicte.py@inserm.fr

DNA viral infection activates danger signals that are transmitted via DNA sensor-STING signaling cascades. Stimulator of IFN genes (STING) is a central adaptor protein that mediates the innate immune responses to DNA virus infection. Although ubiquitination is essential for STING function, how the Ubiquitination/deubiquitination system is regulated by virus infection to control STING activity  remains unknown. We found that USP21 is an important deubiquitinating enzyme for STING and that it negatively regulates  the DNA virus-induced  production of type I interferons by hydrolyzing K27/63-linked polyubiquitin chain on STING. HSV-1  infection recruited USP21 to STING at late stage by p38-mediated phosphorylation of USP21 at Ser538. Inhibition of p38 MAPK enhanced the production of IFNs in response to virus infection and protected mice from lethal HSV-1 infection. Thus, our study reveals a critical role of p38-mediated USP21 phosphorylation in regulating STING-mediated antiviral functions and identifies p38- USP21 axis as an important pathway that DNA virus adopts to avoid innate immunity responses.

 


Vendredi 16/11/2018

11h00

Salle SdT CRC

 

« RNA-protein interactions and the structure of the genetic code »

 

Bojan ZAGROVIC (Department of Structural and Computational Biology University of Vienna, Austria)

Contact : Didier Auboeuf

The relationship between mRNA and protein sequences as embodied in the universal genetic code is a cornerstone of modern-day molecular biology. In this presentation, I will provide evidence supporting a novel claim that the genetic code can actually be seen as a Rosetta stone for understanding RNA-protein interactions in general. Conversely, I will defend a claim that RNA-protein interactions could have been an important driving force behind the origin of the genetic code. Specifically, we have recently revealed a robust, statistically significant matching between the composition of mRNA coding sequences and the nucleobase-binding preferences of their cognate protein sequences. For example, purine-density profiles of mRNA sequences mirror the guanine-affinity profiles of their cognate protein sequences with quantitative accuracy (median Pearson correlation coefficient |R| = 0.80 across the entire human proteome). Overall, our results support as well as redefine the stereochemical hypothesis concerning the origin of the genetic code, the idea that it evolved from direct interactions between amino acids and the appropriate bases. Moreover, our findings support the possibility of direct, complementary, co-aligned interactions between mRNAs and their cognate proteins even in present-day cells, especially if both are unstructured, with implications extending to different facets of nucleic-acid/protein biology.

References

1. Polyansky AA & Zagrovic B (2013) “Evidence of direct complementary interactions between messenger RNAs and their cognate proteins”, Nucleic Acids Research, 41(18), 8434-8443.
2. Polyansky AA, Hlevnjak M & Zagrovic B (2013) “Analog encoding of physicochemical properties of proteins in their cognate messenger RNAs”, Nature Communications, 4, 2784, 1-11.
3. Bartonek L & Zagrovic B (2017) “mRNA/protein sequence complementarity and its determinants: The impact of affinity scales”, PLOS Computational Biology, 13(7), e1005648.
4. Zagrovic B, Bartonek L, Polyansky AA (2018) “RNA-protein interactions in an unstructured context”, FEBS Letters, 592(17), 2901-2916

 

Mardi

20/11/2018
10h30

Amphi Pasteur

“ Breaking the barrier : Lassa virus cell invasion ”

Pr. Dr. Stefan KUNZ (Institute of Microbiology Lausanne University Hospital Switzerland)

contact : sylvain.baize@pasteur.fr

 

The highly pathogenic arenavirus Lassa virus causes a severe viral hemorrhagic fever and is among the most devastating human pathogens. Lassa virus is of zoonotic origin and reservoir-to-human transmission is crucial for spillover into human populations. Host cell attachment and entry are the first and most fundamental steps of every virus infection and represent major barriers for zoonotic transmission. During host cell invasion, viruses critically depend on cellular factors, including
receptors, co-receptors, and regulatory proteins of endocytosis. An in-depth understanding of the complex interaction of a virus with cellular factors implicated in host cell entry is therefore crucial to predict the risk of zoonotic transmission, define the tissue tropism, and assess disease potential. Over the past years, our laboratory investigated the molecular and cellular mechanisms underlying host cell invasion of Lassa virus that uncovered remarkable viral strategies and provided novel insights into
viral adaptation and virus-host co-evolution.

 


                                                                                                                                                                                                                                

 

Mardi
27/11/2018
10h30

Amphi Pasteur

 

“ Antibodies against Ebola and Lassa – Toward broad and potent neutralization ”

 

 

 

 

Erica OLLMAN SAPHIRE (Scripps Research Institut, USA)                                                                                                                             

contact :viktor.volchkov@inserm.fr

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