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L'Unité « RNA Biology and Influenza Viruses » de Nadia Naffakh à l'Institut Pasteur

The RNA Biology and Influenza VIruses (RBIV) Unit was created at the Institut Pasteur on January 1st 2020 for a 5-year period, under the responsibility of Nadia Naffakh. The team currently brings together two permanent researchers (Nadia Naffakh, Catherine Isel) and four talented post-docs from diverse cultures : Magda Cannata-Serio (Italy), Kuang-Yu Chen (Taïwan), David Courtney (Ireland) and Tim Krischuns (Germany). We continue to share premises and to maintain close relationships on a day-to-day basis with our colleagues from Sylvie van der Werf’s research unit. Our research aims at understanding how the influenza virus RNA polymerase  interacts and cooperates with host cell components to control the synthesis, processing and trafficking of the viral mRNAs and genomic RNAs. These interactions represent potential targets for the development of therapeutic antiviral drugs which could be active against a wide range of IAVs and be less likely to select for resistance mutants. Also at stake is a better understanding of the mechanisms that determine the virulence and zoonotic potential of IAVs. We have two major lines of research, focused on the molecular mechanisms of transcription by the viral polymerase and the fate of viral genomic RNAs from nuclear export to packaging into new viral particles.They rely on an inter-disciplinary and collaborative approach that combines molecular virology with structural biology, cellular imaging, microfluidics and bioinformatics.

Zoom sur un jeune chercheur, David Courtney

David Courtney is currently a Marie Curie postdoctoral fellow at the Institut Pasteur, in the lab of Dr Nadia Naffakh. David started his research career at Ulster University in Northern Ireland where he completed a PhD on gene therapy, using both siRNA and CRISPR/Cas9 systems. He then got a position at Duke University, USA in the lab of HIV-1 virologist Prof Bryan Cullen, where he was tasked with exploring the role of the epitranscriptome on influenza A pathogenesis. Over the course of 3 and a half years David published 3 separate studies into common RNA modifications m6A and m5C, and how their presence on viral RNA from influenza A, HIV-1 and MLV, positively regulated translation efficiency and by extension the viral replication cycle. In collaboration with Prof Nicholas Heaton and his lab at Duke University, David demonstrated that an IAV PR8 strain, which was silently mutated to lack m6A motifs on the HA segment, was highly attenuated in vivo, providing further proof of the beneficial nature of these RNA modifications in the viral replication cycle. This could also shed some light on the evolutionary pressure additional RNA viruses, not just IAV, to acquire these seemingly advantageous sites of modification.

Now in his current position at the RBIV Unit at Pasteur under the supervision of Dr Naffakh, David is striving to identify the cellular RNA-binding proteins specifically recruited to IAV mRNAs, such as RNA modifying enzymes for m6A or m5C, that are essential to the IAV replication cycle.

In the near future David is hoping to establish his own research lab back in Ireland using the techniques he has acquired during his time in France and the USA. He aims to better understand the post-transcriptional regulation of both IAV mRNAs and vRNAs, and determine how well these processes are conserved across mammalian and avian species.