Recruitment of 1 engineer in biochemistry/recombinant prot and two PhD students in Immunology
Two PhD student positions in immunology/ rare autoinflammatory diseases (see below for the Engineer position)
Inflammation is a double-edge sword that is key to fight microbes but can also be responsible for chronic autoinflammatory diseases. Inflammasomes are multiprotein complexes that are activated upon sensing of microbial infections or danger signals. Inflammasomes lead to activation of the inflammatory caspase-1, the release of potent proinflammatory cytokines and in most cases to an inflammatory cell death termed pyroptosis.
Gain of function mutations in inflammasome sensor genes can cause rare autoinflammatory diseases in humans. These diseases are characterized by recurrent fevers and by a number of inflammatory manifestations, some being life-threatening.
The research projects will focus on one particular inflammasome, the pyrin inflammasome and on two autoinflammatory diseases associated with mutations in MEFV, the gene encoding pyrin. The pyrin inflammasome detects numerous toxins (e.g. Clostridium difficile toxin B) and pathogenic bacteria (e.g. Yersinia pestis, the agent of plague) and has a well demonstrated antibacterial role. Activation of the pyrin inflammasome is a two step process but the molecular mechanism of step 2, the coupling mechanism between step 1 and 2 and the regulation of these two steps are still poorly understood. A better understanding of the pyrin inflammasome activation mechanisms is key to fully understand its antibacterial role and its pathogenic activation in human diseases and will be the focus of first PhD project.
Mutations in MEFV cause two distinct diseases, Familial Mediterranean fever (FMF) and Pyrin-Associated Autoinflammation with Neutrophilic Dermatosis (PAAND). The causal link between MEFV mutations and human diseases is well established for 7 mutations. Yet, 389 distinct mutations have been identified in MEFV and for most of these mutations, the genotype to phenotype link is unclear. New methodologies are required in order to assess in a comprehensive manner the pathogenicity of the various MEFV mutations and will be developed in the framework of the second PhD project.
The two projects will involve innovative CRISPR/Cas9 approaches, Next Generation Sequencing and experiments on primary cells from patients. These projects are part of collaborative European projects involving clinicians and researchers in the field of immunology, autoinflammatory diseases, geneticists and computing/analytic genomics.
This position is opened in the Centre de Recherche en Infectiologie (CIRI, INSERM U1111) in Thomas Henry’s team. The CIRI is a highly dynamic environment fostering interactions between immunologists, bacteriologists, virologists and clinicians and providing all the necessary platforms and facilities for the project. This position is opened starting in Autumn 2022 for three years.
For more information and to apply for this position, please contact Thomas HENRY (thomas.henry@inserm.fr). The call will be closed on july the 15th at the latest but may be closed earlier if two candidates are identified earlier. Please include a cover letter addressing your interest in the position along with your CV, summary of your research experience and contact information of two professional references.
Recruitment Biochemical Engineer
The team "Inflammasome, bacterial infections and autoinflammation" led by Thomas Henry at CIRI in Lyon is looking for an assistant engineer or an engineer in biochemistry-recombinant protein production-interaction tests. The person recruited will be in charge of developing the experimental approaches in biochemistry of the team in connection with the "Protein Science Facility" of the SFR Biosciences.
The person recruited will be in charge of producing several recombinant eukaryotic and prokaryotic proteins and of carrying out crystallization, protein-protein interaction and protein-small molecule interaction tests.
In addition to a close collaboration with the "Protein Science Facility" of the SFR Biosciences, depending on the results obtained, the person recruited will collaborate with a crystallographer and/or a cryomicroscopy team.
The techniques used for the production of recombinant proteins will be the classical expression techniques in E. coli followed by purification steps by chromatography and quality control by biophysical methods. Crystallogenesis will also be performed on the SFR Biosciences robotic platform. The interaction tests will involve co-purification approaches, characterization of interactions by several techniques such as interferometry (BLI), microscale thermophoresis (MST/NanoTemper), surface plasmon resonance (SPR/Biacore).
The scientific themes will focus on two main topics: 1) the type VI secretion system of the bacterium Francisella tularensis and its effectors which are virulence factors of this pathogenic bacterium 2) proteins of innate immunity to fight against bacteria.
We are looking for a candidate with experience in recombinant protein production and purification. The person will be recruited by Inserm via a fixed-term contract of one year, renewable, whose remuneration will follow the Inserm grids and will depend on the candidate's qualifications and experience. All profiles will be considered from technician to engineer. We are looking for a rigorous person with an appetite for developing new techniques. The person recruited will interact with many people in the team, in the SFR Biosciences platforms and with collaborators, so we will pay particular attention to the communication skills of the person recruited.
The position is to be filled immediately for a start of contract in early May or early June (with some flexibility depending on the profile of the candidates). To apply, candidates are invited to send their CV and cover letter to Thomas Henry (mailto:Thomas.henry@inserm.fr). If possible, please include the contact information of one or two people who can recommend the candidate.