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3-year thesis contract (80 premium) in Virology and novel imaging techniques (equal gender opportunity)

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

Date Limite Candidature : lundi 11 juillet 2022

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General information

Reference : UMR9198-YVEGAU-008
Workplace : GIF SUR YVETTE
Date of publication : Monday, June 20, 2022
Scientific Responsible name : Yves Gaudin (Département de Virologie de l'I2BC) , Ignacio Izeddin et Olivier Thouvenin (Institut Langevin, ESPCI, CNRS, PSL)
Type of Contract : PhD Student contract / Thesis offer
Contract Period : 36 months
Start date of the thesis : 1 October 2022
Proportion of work : Full time
Remuneration : 2 135,00 € gross monthly

Description of the thesis topic

Many viruses form specialized compartments, called viral factories, which house certain stages of their replication in the infected cell. In the case of the Mononegavirales, these factories behave like membrane-less liquid organelles, formed by liquid-liquid phase separation, which allows the segregation of viral proteins and prevents the immune defenses from accessing them.
Moreover, the viral infection also induces in the cell the formation of condensates of cellular proteins regulating innate immunity.
More generally, the formation of protein condensates by phase separation has recently emerged as a general spatio-temporal control mechanism of biological activity in the cell. This would ensure the specificity and efficiency of cellular biochemical reactions. The study of these condensates is a largely fundamental and general subject to many biological systems.
Due to their physico-chemical properties, these organelles and liquid condensates are sensitive to cell attachment. This requires working on living cells with fluorescent versions of the proteins involved, which may have different properties from the wild-type protein. Therefore, fluorescence optical imaging techniques are not always suitable for observing these structures.
This project aims to develop new endogenous microscopy to characterize the factories of the rabies virus. By exploiting different minimal systems, recapitulating the properties of viral factories and able to be imaged without particular confinement conditions, it aims to develop a microscope combining high-resolution endogenous optical imaging, fluorescence microscopy and FRAP. This project will allow the quantification of the formation and dynamics of viral factories and their interactions with the components of innate immunity which themselves are able to combine into condensates with liquid properties.

Work Context

This thesis is funded by the CNRS as part of the 80 prime program. The student will work within the framework of a collaboration between a team of virologists working within the Institute of Integrative Biology of the Cell (I2BC) and a team of physicists in interaction with biologists and doctors belonging to the Institute Langevin, ESPCI Paris – PSL..
The I2BC team (https://www.i2bc.paris-saclay.fr/rhabdovirus/) is recognized for its work in molecular, cellular and structural virology, particularly in the areas of rhabdovirus entry, factories formed by the rabies virus and their interactions with innate immunity. It is made up of three statutory researchers, a lecturer and two engineers and currently hosts 2 post-docs, two doctoral students and an engineer on a fixed-term contract. She belongs to the Department of Virology of the I2BC (https://www.i2bc.paris-saclay.fr/disciplinary-department/virology-department/). The student will therefore have access to all the facilities of the department and will also benefit from the many technological platforms of the Institute, in particular that of imaging.
Team 2 of the Langevin Institute, ESPCI Paris - PSL is a team of imaging physicists for Biology and Medicine. She is recognized for the development of label-free optical imaging tools, and single molecule and superresolution microscopy. These include the detection and characterization of nanometric viruses, the dynamic tomography of organoids, and the monitoring of molecular dynamics in the nucleus. It is made up of two teacher-researchers in optics, two professors emeritus (in physics and virology). She joined a biomedical imaging group, with about ten students and post-docs. It belongs to the Langevin Institute (https://www.institut-langevin.espci.fr/home), a laboratory specializing in the physics of waves, optics, acoustics, electromagnetism.

Constraints and risks

Work within the I2BC will be conducted in an L2 environment. The project involving the manipulation of the rabies virus requires the vaccination of the student. Work at the Langevin Institute involves the use of class 3 and 4 lasers.

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