PhD Position (M/F) – Single-Molecule Imaging of Viral RNA During Arbovirus Infection

Job Description

Thesis Subject

Deciphering Viral RNA Translation and Replication Dynamics in Vivo at Single-Molecule Resolution

Arthropod-borne viruses (arboviruses) such as Zika virus (ZIKV), Chikungunya virus (CHIKV) and Sindbis virus (SINV) represent an increasing global public health threat due to their rapid geographic expansion and recurrent outbreaks. Despite major advances in arbovirus research, the molecular mechanisms that regulate viral gene expression during infection remain poorly understood. In particular, how viral RNAs dynamically coordinate translation and replication in living cells, and how these processes are controlled by viral RNA cis-regulatory elements, remains largely unexplored.

This PhD project aims to decipher the molecular logic governing arbovirus RNA expression in vivo by combining molecular virology, quantitative biology and state-of-the-art single-molecule imaging. A major objective is to determine how the highly structured 5′ and 3′ untranslated regions (UTRs) orchestrate the transition between translation and replication, thereby regulating viral fitness and host adaptation.

The project will be carried out within the MDVA team under the joint supervision of Dr. Jérémy Dufourt (RNA dynamics and single-molecule imaging) and Dr. Jim Zoladek (flavivirus biology and RNA stability). The candidate will develop interdisciplinary expertise spanning molecular biology, genetics, biochemistry, live-cell microscopy and quantitative image analysis.

The first objective will be to establish quantitative reporters enabling direct visualization of viral RNA translation at single-molecule resolution. Using engineered viral RNA constructs carrying translation reporters, the candidate will investigate how viral UTRs regulate translation efficiency, initiation and elongation kinetics, as well as the spatial organization of protein synthesis in living cells and zebrafish embryos. These experiments will reveal how RNA sequence and structural elements encode translational output in their physiological context.

A second objective will consist of generating recombinant fluorescent arboviruses (ZIKV, CHIKV and SINV) that enable simultaneous visualization of viral genomes, translation and replication. By combining RNA-labeling strategies with fluorescent translation reporters, the project will provide real-time observation of the transition between translation and replication during infection. These approaches will establish, for the first time in a vertebrate model, a comprehensive view of arbovirus RNA dynamics with high spatial and temporal resolution.

A central feature of this project is the use of zebrafish embryos as an in vivo infection model. Their optical transparency, genetic tractability and conserved innate immune system make them ideally suited for quantitative live imaging of virus-host interactions in a physiological environment. Advanced microscopy and computational image analysis will be used to quantify viral RNA behavior throughout infection and to determine how translation and replication are coordinated within infected tissues.

Overall, this project will establish an innovative framework to investigate arbovirus gene expression in vivo at single-molecule resolution. Beyond providing fundamental insights into viral RNA regulation and host-pathogen interactions, it will develop broadly applicable methodologies to study dynamic gene expression in living organisms. The PhD candidate will receive interdisciplinary training at the interface of virology, RNA biology, advanced microscopy and quantitative image analysis, within an internationally competitive research environment

Your Work Environment

Situated within the Institut de Recherche en Infectiologie de Montpellier (IRIM), the MDVA team is dedicated to addressing fundamental biological/virology questions through the development and application of innovative methodologies. The PhD candidate will benefit from the team's expertise and have access to the local BSL3 containment facility (CEMIPAI), zebrafish (ZEFIX), and imaging (MRI) platforms to fully support their research objectives.
The MDVA team is fully supported by 4 ANR (NanoLipoVirus, RSVMLipo, VISA, DyViZe) and 1 PEPR ANRS-MIE. Part of this project is financially supported by the ANR Dyvize (PI: J.Dufourt).

Constraints and risks

Work involving infectious arboviruses in a biosafety laboratory (BSL-2 and/or BSL-3 depending on the viral strains and institutional regulations).
Regular use of advanced microscopy platforms and quantitative imaging facilities.
Experimental work involving zebrafish embryos in accordance with institutional and ethical regulations.
Interdisciplinary project requiring expertise in molecular biology, virology, microscopy and quantitative data analysis.
Occasional flexible working hours to accommodate live-imaging experiments and time-course infection assays.

Compensation and benefits

Compensation

2300 € gross monthly

Annual leave and RTT

44 jours

Remote Working practice and compensation

Pratique et indemnisation du TT

Transport

Prise en charge à 75% du coût et forfait mobilité durable jusqu’à 300€

About the offer

About the CNRS

The CNRS is a major player in fundamental research on a global scale. The CNRS is the only French organization active in all scientific fields. Its unique position as a multi-specialist allows it to bring together different disciplines to address the most important challenges of the contemporary world, in connection with the actors of change.

CNRS

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