General information
Offer title : Post-doctoral researcher in cellular membrane remodelling induced during poxvirus infection (M/F)
Reference : UMR9198-SOLSTR-001
Number of position : 1
Workplace : GIF SUR YVETTE
Date of publication : 06 February 2023
Type of Contract : FTC Scientist
Contract Period : 24 months
Expected date of employment : 1 April 2023
Proportion of work : Full time
Remuneration : monthly gross salary from 2889 € and 4082 € according experience
Desired level of education : PhD
Experience required : 1 to 4 years
Section(s) CN : Molecular and structural biology, biochemistry
Missions
Depending on the interests of the applicant, the project can focus on various aspects. The post-doc should contribute:
• To study the role and structure of viral proteins essential for the assembly of the viral membrane using Vaccinia virus as a model for poxviruses
• To set-up a cell-free protein expression system from extracts of reticulocytes coupled to microsomes or wheat germ for the production and purification of the viral proteins together with their partner(s)
• To set-up and optimize based on these samples, protocols for cryo electron microscopy: sample preparation, data collection and processing for tomography and single-particle analysis
• To analyse the data, communicate findings at national and international meetings, and prepare scientific publications
Activities
Main activities:
- Molecular biology: cloning ; expression of recombinant proteins (E. coli, HEK cells, cell-free, etc.) ; purification of macromolecules
- Biochemistry: protein-protein or protein-lipid interactions ; work with model membrane systems (liposomes, microsomes, etc.)
- Structural biology: cryo electron microscopy for tomography and single particle analysis ; X-ray crystallography
- Cell biology: cell culture (HeLa, Vero, BSC-1, HEK, etc.) ; transfection ; stable cell lines
- Virology : infection ; virus production and purification
Other activities:
- Project management
- Supervision of undergraduate and graduate students
- Contribution to the supervision of PhD students
- Share of lab responsibilities
Interdisciplinary profiles at the interface between virology, biochemistry, membrane biology or molecular and structural biology are a plus.
Skills
Applicants should hold (or be about to defend) a PhD in biology with key expertise in virology, biochemistry, molecular or structural biology. Ideally, candidates should also have published one or several primary research articles as a first/co-first author, which are somehow related to the field of the proposed research.
Expected theoretical and practical knowledge:
- Strong skills in molecular biology regarding cloning, expression and purification of recombinant proteins
- Some experience on work with membrane proteins, use of membrane model systems (e.g. liposomes, microsomes, etc.) or on the analysis of protein-protein or protein-lipid interactions
- Previous acquaintance with cryo electron microscopy, either tomography or single particle analysis regarding sample preparation, data collection or data processing, or with X-ray crystallography
- Experience with cell culture (e.g. HeLa, HEK)
- Knowing of basic virology techniques like infection, production and purification of viral particles
- Fluency in english, speaking and writing
Abilities:
- Implement and write protocols based on specific material and equipment while using dedicated software
- Drafting quality, ability to develop a scientific project, to publish and to promote the conducted research
- Capacity to work in a team and contribute to interdisciplinary projects
- Work independently, organizational skills and accountability
- Supervision and training of students
Know-how :
- Interpersonal skills
- Organization and planning
- Meticulous and reliable
- Independence
- Intellectual and scientific curiosity
Work Context
The post-doc will work in the group "Replication and assembly of poxviruses" in the Virology department at the Institute for Integrative Biology of the Cell (I2BC). I2BC is a joint research unit affiliated with the CNRS (UMR9198), CEA and University Paris-Saclay, with about 650 employees in total. The institute represents a highly rich and dynamic scientific environment with 60 research groups organized in 5 scientific departments, 15 top technological facilities.
The team works on poxviruses and focuses on the molecular mechanisms controlling host cell remodelling during infection by these pathogens. The research project aims at improving our understanding of the mechanism underlying the viral assembly in the case of Vaccinia virus. The goal is to determine the role and the structure of viral proteins that are known to be essential for the formation of the viral membrane. Vaccinia virus represents an ideal working model being the type species of the Poxviridae family with a lot of molecular tools available. As for all poxviruses, the infection cycle takes place directly in the cytoplasm and leads to a massive reoarganization of the host cell. Assembly of progeny virions in particular, is based on a unique mechanism of viral membrane formation. Current working model includes the recruitment of vesicles derived from the endoplasmic reticulum to the assembly site, where they are ruptured open and form typical crescents with open membrane ends. After packaging of the viral genome, the crescents are closed, thereby forming the immature viral particles, which need to undergo further maturation steps to form the mature infectious particles. The long-term goal is to uncover the molecular mechanisms that regulate these processes and remain poorly understood.
The head of the lab started in December 2021 in the Virology department at I2BC. She got funding from ATIP-Avenir in 2022 to continue her research on poxviruses. Bringing a new research topic at the forefront and a new working model highly relevant, the group "Replication and assembly of poxviruses" also combines expertise in virology and structural biology with innovative approaches in integrative imaging: cryo electron microscopy and correlative techniques applied to study viral infections. The proposed project contributes to the implementation of in vitro approaches to analyse viral proteins that are essential for cellular membrane remodelling triggered during poxvirus infection. Importantly, these approaches are also complementary to the work of two PhD students in the group.
The group fits nicely into the research carried out in the Virology department on the molecular mechanisms underlying viral infections, formation of viral factories and antiviral defences. In addition, it contributes to the implementation of the structural cell biology performed in situ at I2BC via strong interactions with the facilities of Imagerie-Gif and other labs in the framework of several internal research programs. On the Paris-Saclay campus, the team also takes part in the working goup on the development of cryo electron microscopy with the installation of a Glacios (I2BC) and Titan Krios (Synchrotron Soleil) microscopes in 2023 in BSL2. More globally, the group has many collaborations locally, nationally and internationally.
Constraints and risks
There will be short trips on the campus of Paris-Saclay (e.g. Synchrotron Soleil, UP-Saclay, CEA) as well as eventually, short visits to collaborators in France or abroad.
For experiments on Vaccinia virus, the post-doc should receive apropriate training to work in BSL2 lab.
Apply
https://emploi.cnrs.fr/Offres/CDD/UMR9198-SOLSTR-001/Default.aspx?lang=EN
