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Reference : UMR8197-NATBOI-064
Workplace : PARIS 05
Date of publication : Thursday, April 15, 2021
Type of Contract : FTC Scientist
Contract Period : 24 months
Expected date of employment : 1 September 2021
Proportion of work : Full time
Remuneration : Between 2800 and 3800 € monthly gross salary according to experience
Desired level of education : PhD
Experience required : 1 to 4 years
The food-borne pathogen Listeria monocytogenes (Lm), which is the cause of listeriosis, can enter and proliferate in most human cell types and spread to neighbouring cells, using virulence factors that target diverse cellular components and thereby hijack host cell functions. After entering epithelial cells, Lm has been classically described to exit rapidly internalisation vacuoles and lead a cytosolic lifestyle. However, our team has recently shown that about 10% of bacteria remained more than an hour in vacuoles, and even proliferated therein as rapidly as in the cytosol (Peron-Cane et al. PLoS Pathog. 2020). We now intend to better characterise the host and bacterial mechanisms that allow Lm to inhabit these vacuoles, and the consequences of this novel niche on infection.
At the crossroads of cellular biology and infection biology, using live microscopy approaches, the recruited post-doctoral researcher will aim at identifying the mechanisms of biogenesis and maintenance of these novel replication and signalling compartments, and their contribution to the infectious process. A special emphasis will be given to the contribution of host cell trafficking and organelle dynamics, and to the perturbation of these processes by Lm-secreted effectors. In collaboration with the team of Nicolas Desprat in the Physics department of ENS, they will also develop a model of Lm cell colonisation strategies that takes into account cytosolic and vacuolar lifestyles.
The candidate will contribute to defining the research strategy, conducting experiments, analysing results and participating to research dissemination around the research topic. They will also participate in all aspects of the team life, be given the opportunity to present their project in international meetings and publish the results of their work.
Experimentation will involve the observation of Lm-infected cells in live microscopy (and on fixed samples). For instance, cell trafficking markers (membrane markers from source organelles; calcium signalling; cytoskeleton drivers) will be tracked, with regards to vacuole biogenesis, long-term maintenance and growth. Intervention strategies (chemical inhibitors, bacterial mutants) will be used to infer potential mechanisms underlying our observations. The FAST fluorogenic reporter system will also allow a live monitoring of the expression and secretion of virulence factors, and their tracking. Experiments will be devised in a quantitative biology framework, aiming at feeding the models of our collaborators in biophysics with informative parameters.
Altogether, this project will allow the candidate to thrive gradually as an independent scientist on the study of host-pathogen interactions dynamics at the molecular and cellular levels, while characterizing a novel replication niche for Lm and thereby providing precious information about the mechanisms and dynamics of Lm intravacuolar lifestyle.
The candidate should hold a PhD in microbiology, cell biology or biophysics, preferably with a previous experience on cellular models of host-pathogen interactions/infection dynamics and/or on live approaches to cellular trafficking. A taste for interdisciplinary research is paramount. Training will be provided on-site for approaches specific to our group.
The ability of the candidate for teamwork, a strong sense of organisation and initiative, as well as written and spoken communication skills in English, are critical.
The Institute of Biology of École normale supérieure (IBENS) is a fundamental research centre in Life sciences. Our research aims at deciphering the fundamental mechanisms at the core of biological processes.
IBENS (ENS, CNRS and Inserm joint unit) hosts over 300 people in 30 autonomous teams. The research environment is highly collaborative and interdisciplinary, and combines experimental and theoretical approaches. Our activities cover fields as various as functional genomics, neurobiology, developmental biology, ecology and evolution biology.
Several technological platforms, notably in imaging, genomics, computational biology and proteomics, provide a robust support to the activities of the different teams. Our research also benefits from the high potential of interactions with other scientific departments in ENS (physics, chemistry, mathematics, informatics, etc.). ENS is deeply involved in the formation of students and young researchers at all levels.
The host team (Bacteria infection & RNA Destiny, https://www.ibens.ens.fr/?rubrique26&lang=en) is headed by Alice Lebreton (INRAE researcher). Our research in cellular microbiology focusses on the model intracellular bacterium Listeria monocytogenes, with a special interest for the spatiotemporal dynamics of the molecular crosstalk between bacteria and host cells. Our research combines molecular biology, functional genomics, cellular biology, bacterial genetics and chemical biology approaches, with the aim of providing a better understanding of the mutual requirements for bacteria-host niche adaptation, leading to the characterization of new virulence factors, and gaining insight into the intracellular lives of Listeria and the dynamics of its secreted virulence factors in real-time microscopy (Peron-Cane et al. PLoS Pathog. 2020; Chekli et al. Sci Rep. 2020).
In the ANR-funded LivaLife consortium, the candidate will frequently interact with our long-term collaborator on biophysics Nicolas Desprat (ENS, Physics department) and with the engineer who will be recruited in his team for analysis and modelling approaches, as well as with or collaborators involved in the in vivo part of the study in Institut Pasteur.
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