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Stages, thèses, post-doctorat

Master degree/PhD degree/ Postdoctoral training

 

Specific subjects :

IDENTIFICATION OF RETROVIRAL PROTEINS INHIBITING NMD : from viral inhibition to NMD deciphering

 

PhD proposition  : 

CONTEXTE / CONTEXT

In the past, we showed that the viral protein Tax from HTLV-1 inhibits the nonsense mediated mRNA decay (NMD) surveillance pathway by interacting with the RNA helicase UPF1 (Mocquet et al. JVI, 2012, Fiorini et al., Nature Communications 2018). However it emerged recently that the viral protein Rex may also interfere with this mRNA decay pathway in a different way than Tax.

Preliminary data already identified a cellular target (CRM1) that may link NMD and Rex. Interestingly, with another set of preliminary results, we found that the retroviral protein Rev from HIV (that has overlapping functions with Rex) is also able to inhibit NMD.

Those data (and others) converge to present the retroviruses mRNA as targets for the mRNA degradation pathway named nonsense-mediated mRNA decay (NMD) although each retrovirus seems to have evolved specific countermeasures against it. In the meantime it is now clear that NMD is a major actor of the post-transcriptional regulation allowing a correct homeostasis in gene expression.  (Mocquet et al, AIDS Res Hum Retroviruses, 2015).

  -      PROJET / PROJECT

This project aims to define the importance of the NMD during retroviral infection through the description of how this RNA degradation pathway is controlled by the human retroviruses. More specifically, we plan to describe and compare the molecular mechanisms of NMD inhibition by the proteins Rex and Rev from HTLV and HIV respectively. To do so, we plan to first check the state of NMD in infected cells (WP1). Then we plan to characterise the involved viral proteins and their modus operandi (WP2). Finally we will screen the impact of NMD inactivation in HIV-1 and HTLV-1 by high-throughput approaches, characterising mRNA stability modifications, alternative splicing reprogramming and translation modulations (WP3).

-      Techniques utilisées/Methods:

Directed mutagenesis, cell culture, transient transfections, western blot, mRNA half-live analysis, RNA immunoprecipitation, RTqPCR, confocal microscopy, RNA seq library and analysis.

 

 

IMPACT OF NMD DURING HUMANIZED MICE INFECTION BY HTLV-1.

 

Additionnally,

Possibilities of master student internships, PhD and Postdocs can be discussed for each of the research axis of the team.

 

 

Contact Pierre Jalinot (pierre.jalinot[at]ens-lyon.fr) , Madeleine Duc Dodon (madeleine.duc.dodon[at]ens-lyon.fr) or directly each of the researcher in charge of a specific research axis.