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M/F - PhD position in Molecular Virology

This offer is available in the following languages:
Français - Anglais

Date Limite Candidature : vendredi 19 août 2022

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General information

Reference : UMR9004-JEAPEL-005
Date of publication : Friday, July 29, 2022
Scientific Responsible name : Jean-marie Peloponese & Laurent Chaloin (co-direction)
Type of Contract : PhD Student contract / Thesis offer
Contract Period : 36 months
Start date of the thesis : 3 October 2022
Proportion of work : Full time
Remuneration : 2 135,00 € gross monthly

Description of the thesis topic

The recent SARS CoV-2 outbreak has highlighted the importance of developing new strategies to combat emerging and re-emerging viral infections. Certain cellular factors such as RNA helicases are necessary for the smooth running of infectious cycles and represent potential antiviral targets. Helicases separate the double helix made of DNA or RNA and allow cellular proteins to access, read or rearrange genetic information. Our observations suggest that among cellular helicases, DHX9 is one potential therapeutic target. In collaboration with Dr. Briant and Dr. Chaloin from the Montpellier Infectious Diseases Research Institute (IRIM), we have therefore developed small molecules capable of binding to DHX9 and inhibiting its activity.
DHX9 is an SF2-like helicase. It has been described as interacting with RNA polymerase II, transcription factors and coactivators to modulate the transcription and translation of selected genes. By interacting with viral genomes and/or viral proteins, DHX9 also promotes the multiplication of a range of phylogenetically unrelated RNA viruses such as Chikungunya virus (CHIKV), dengue virus (DENV), Zika virus (ZIKV), human immunodeficiency virus (HIV-1), human T-cell leukemia virus type 1 (HTLV-1). With the exception of HIV-1 and HTLV-I for which numerous publications show that DHX9 promotes the viral cycle by regulating the transcription and translation of viral genes, the molecular basis of its proviral activity for RNA viruses does not is not well known. In light of these observations, the thesis project aims to extend our knowledge of the key proviral role played by DHX9 during RNA virus replication and to better understand the mode of action of these small molecules.

The doctoral student will study the impact of our molecules on the cell localization of DHX9 during infection by CHIKV, DENV and SARS-CoV-2. The doctoral student will characterize the interactions of DHX9 with the different viral RNAs and viral proteins using various molecular and cellular biology techniques such as RNA-IP and iCLIP, RNA-seq and imaging technologies by smiFISH. In parallel, the PhD student will carry out a structural study in order to better understand the mechanisms of DHX9 inhibition by small molecules and also to characterize the interactions between DHX9 and cellular or viral partners.

Work Context

The doctoral position is funded by the ANR (3 years) and the Ph.D. student will be hosted by the Actors in the pathogenesis of retroviral infections (APIR) team at the Montpellier infectious disease research institute (IRIM) in Montpellier (France)

Constraints and risks

Work in L3 Laboratory

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