1-year contract renewable (EvoCure 3+ years)
CIRI (Ecole Normale Superieure de Lyon)
Start : From May 2025
Cell-autonomous innate immunity is the first line of defense against pathogens in all living organisms. It was recently discovered that some human antiviral defense proteins are part of « ancestral immunity » shared between eukaryotes and prokaryotes [1-3]. We believe that this is just the tip of the iceberg, and we now want to use these concepts by inverting the discovery scheme. In this project, the aim is to discover new antiviral innate immune factors in mammals, based on newly-identified defense systems in prokaryotes. After high-throughput antiviral screening, the postdoc will characterize the mechanisms of action and evolution of new immune players [4-5].
References (* our lab, ∂ EvoCure collaborators) 1∂. Bernheim et al., Plos Biol (2024). https://doi.org/10.1371/journal.pbio.3002717 2∂. Rousset, Trends Immunol (2023). https://doi.org/10.1016/j.it.2023.10.001 3. Ledvina and Whiteley, Nat Rev Microbiol (2024), https://doi.org/10.1038/s41579-024-01017-1 4*. Jacquet et al., Science Advances (2022). https://doi.org/10.1126/sciadv.add7540 5*. Legrand et al., Plos Biol (2024). https://doi.org/10.1371/journal.pbio.3002696
Inserm is the only French institute entirely dedicated to biological, medical and population health research. It has research laboratories throughout France. Our institute brings together 15,000 researchers, engineers, technicians and administrative staff, with a common goal: to improve the health of all through advances in knowledge about living organisms and diseases, innovation in treatments and public health. Joining Inserm means joining an institute committed to parity and professional equality, diversity and support for its employees with disabilities, from recruitment onwards and throughout their careers. To preserve well-being at work, Inserm pursues an active policy in terms of working conditions, based in particular on a fair balance between personal and professional life. In 2016, Inserm was awarded the European HR Excellence in Research label and is committed to developing its recruitment and evaluation practices for researchers.
Host structure
Center: Centre International de Recherche en Infectiologie (Inserm U1111).
CIRI is a leading research center jointly affiliated with Inserm, CNRS, ENS Lyon and Université de Lyon Claude Bernard. CIRI brings together 500 scientists with expertise ranging from molecular virology to human immunology.
The postdoc will join the group « Functional evolution of virus-host interactions, and impact on cross-species transmission » led by Lucie ETIENNE, within the LP2L team located on the ENS Lyon campus. The group aims to better understand molecular interactions and co-evolution between viruses and mammals. It comprises 3 PhD students, 1 Marie-Curie MSCA postdoctoral fellow, 2 engineers and 1 Master’s trainee, and is part of the wider LP2L team.
The Center has gold-standard equipment required for the project (BSL2-3, microscopy, flow cytometry, sequencing, biocomputational hub…) with the support of UMS BioSciences and CBPsmn
Description of the position
The project: Cell-autonomous innate immunity is the first line of defense against pathogens in all living organisms. It is crucial against viral infections, cross-species transmissions, but also in cancer and autoimmunity. Recent advances in antiphage defense from prokaryotes and in predicted protein structure homology searches have allowed the identification of “ancestral immunity” [1]: immune proteins shared by different organisms throughout the tree of life. Structural and functional analogs of mammalian immune factors have recently been identified in prokaryotic antiviral proteins, such as cGAS/STING, gasdermins. Some of them even share an extremely ancient and common evolutionary history, such as Viperin [2-3]. Our lab has identified some other examples of human antiviral immune protein domains, which have homologs in antiphage proteins of bacteria [unpub]. Yet, we believe this is only the tip of the iceberg, and we now want to use these concepts to invert the discovery scheme. In this project, we aim to start from newly-identified defense systems of bacteria to discover antiviral innate immune factors in mammals.
In collaboration with the Inserm Impact EvoCure consortium, the postdoctoral fellow will perform an original homolog gain-of-function screen of selected candidates to identify novel mammalian antiviral factors, with the help from the EvoCure Engineer (i.e. senior research technician). He/she will then choose one or several candidate proteins and characterize their immune roles, molecular mechanisms of action in mammals, and their evolutionary history [4- 5]. We expect to uncover previously-unknown actors of mammalian innate immunity, which have been important over deep evolutionary times and may play key roles in modern pathology and viral reservoir hosts.
References (* our lab, ∂ EvoCure collaborators) 1∂. Bernheim et al., Plos Biol (2024). https://doi.org/10.1371/journal.pbio.3002717 2∂. Rousset, Trends Immunol (2023). https://doi.org/10.1016/j.it.2023.10.001 3. Ledvina and Whiteley, Nat Rev Microbiol (2024), https://doi.org/10.1038/s41579-024-01017-1 4*. Jacquet et al., Science Advances (2022). https://doi.org/10.1126/sciadv.add7540 5*. Legrand et al., Plos Biol (2024). https://doi.org/10.1371/journal.pbio.3002696
Main activities
- Develop innovative, interdisciplinary research projects in collaboration with other team members
- Design and implement experimental and bioinformatics techniques: molecular virology of
- RNA and DNA viruses, cell biology, innate immunity in non-model mammalian cells such as bats or non-human primates, phylogenetic analyses, protein structure prediction analyses…
- Analyze results and communicate them at conferences and in publications.
- Train new trainees.
Skills
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- Molecular and cellular biology, Virology, Innate immunity, Evolutionary biology, Phylogenomics and/or Bioinformatics
- Interdisciplinary skill set
- Previous experiences in: high-throughput approaches (CRISPR screens, exogenous library screens), mechanistic characterization of protein functions, phylogenomic analyses, protein structure prediction or NGS data analyses (python, R).
- Autonomy, collaborative work, excellent written and oral communication skills
Past experience
- Scientific publications in international peer-reviewed journals (at least 1 preprint or first author article).
- Experience in supervising trainees or staff.
Training • PhD in Life Sciences
More contract info.
• Fixed-termed contract: 1 year renewable (3 years with possible extension)
• Starting date to be discussed, from May 2025
• Salary according to national standards, with benefits (collective catering, partial reimbursement of transport fees, supplementary health insurance)
How to apply ?
Application By February 28th, 2025
Send (i) a CV, (ii) contact details (name, email) of 2-3 referees, (iii) a cover letter to Lucie Etienne.