MOLECULAR MECHANISMS CONTROLLING EFFECTOR B CELL DIFFERENTIATION
Team “Immunity in Health and Disease”,
Institut Necker Enfants Malades (INEM), Paris, France
INEM is a biomedical research center aiming at fundamental discoveries with potential therapeutic implications. Our international faculty includes 19 teams and two departments: “Cell Biology (Growth and Signaling)” and “Immunology, Infectiology, and Haematology”.
INEM, together with the IMAGINE institute and the Hôpital Necker-Enfants Malades, make up the Necker campus which, supported by state-of-the-art core facilities, provides a vibrant environment for basic research and translational innovation. The Campus has a long-standing reputation for scientific excellence (8 principal investigators (PIs) at INEM received ERC awards) and key pioneering medical contributions (e.g. transplantation, biotherapy, gene therapy).
The team “Immmunity in Health and Disease” is investigating how B cells are involved in autoimmune and infectious diseases. We previously found that B cells could regulate immunity through the provision of IL-10 and IL-35 (Nature Immunology 2002, Immunity 2010, Nature 2014, Immunity 2018), and established that the major B cell subsets producing these cytokines in vivo were two distinct subsets of antibody-secreting cells (Immunity 2010, Nature 2014, Immunity 2018). We furthermore demonstrated that B cells contributed to the pathogenesis of autoimmune disease through the production of IL-6 (J Exp Med 2012).
The current project will investigate the molecular mechanisms controlling effector B cell differentiation and function, combining state-of-the-art proteomics, genetics, and microscopy approaches. These studies will be performed using experimental models and human cells. The goal is to identify novel molecular checkpoints controlling effector B cell differentiation and function to refine both our comprehension of B cell immunity and their therapeutic targeting.
The candidate should have a strong track record in molecular immunology or molecular biology.
The position is open. Salary will be according to experience following INSERM regulation.
Please send your application via email in English with CV, a brief outline of previous research, and contact details of three references to: email@example.com ; firstname.lastname@example.org
INEM- Team – Immunity in Health and Disease
156-160, rue de Vaugirard
Selected publications from the team:
Lino AC. et al. Immunity. 2018. vol. 49 p120-133.
Kieback et al. Immunity. 2016. vol. 44 p1114-1126.
Shen et al. Nature Reviews Immunology. 2015. vol. 15 p441-451.
Shen P. et al. Nature. 2014. vol. 507 p366-370.
Neves P. et al. Immunity. 2010. vol. 33 p777-790.
Fillatreau S. et al. Nature Reviews Immunology. 2008. vol. 8 p391-397.
Fillatreau S. et al. Nature Immunology. 2002. vol. 3 p944-950
The Institut Necker-Enfants Malades (INEM; https://www.institut-necker-enfants-malades.fr/index.php) is a biomedical research center aiming at fundamental discoveries with potential therapeutic implications, with a focus on incurable chronic diseases. Our international faculty includes 19 teams and two departments: “Cell Biology (Growth and Signaling)” and “Immunology, Infectiology, and Haematology”.
INEM, together with the IMAGINE institute and the Hôpital Necker-Enfants Malades, make up the Necker campus which, supported by state-of-the-art core facilities, provides a rich and vibrant environment for basic research as well as translational innovation. The Campus has a long-standing reputation for scientific excellence (8 principal investigators (PIs) at INEM received ERC awards) and key pioneering medical contributions (e.g. transplantation, biotherapy, gene therapy).
PIs at INEM have first-rate expertise in basic physiology, cellular biology, and molecular biology. The INEM teams collaboratively address multiple facets of human diseases including the often-overlooked fact that enduring pathologies generally involve multiple organs and physiological systems, associating deregulations in inflammation, immunity, metabolism, and inter-organ hormonal communications. The interdisciplinary expertise assembled at INEM uniquely permits the holistic understanding of complex diseases, takes into account the interaction with the environment and works to facilitate translation for innovative treatments to improve patients’ lives. To achieve this, the close ties and continuous interaction of the INEM teams with the clinical services of the Hôpital Necker-Enfants Malades are both a fundamental element and a critical asset.
INEM is now seeking to complement its scientific teams by recruiting a new junior or established group leader in areas relevant to its mission, who combines scientific excellence in fundamental research approaches with a strong interest in disease-relevant investigation. Outstanding candidates meeting these criteria and applying recent holistic approaches in immunology, including but not limited to human immunology, systems immunology, autoimmunity and immunometabolism will be preferentially considered. Nonetheless, outstanding candidates working in virology, hematology, bioinformatics, cell biology, molecular biology, and physiology are also encouraged to apply. The selected candidate will be offered laboratory and office space at INEM, access to all technological platforms of the Necker Campus (cytometry, imaging, proteomics, metabolism, bioinformatics, animal facility, biobank, etc.), and a competitive starting package. He/she will also receive assistance for attracting funding and establishing collaborations within the Necker Campus, the Université de Paris and the broader Paris area, one of the major science hubs in Europe.
Candidates must have a PhD, MD or MD/PhD. Applicants should submit their curriculum vitae, as well as a brief description of research accomplishments and plans for future scholarly work. These, along with the names of three references, should be submitted by August 31, 2020 to email@example.com.
A PhD position is available for the project “Identifying inducers of secretory leukocyte protease inhibitor (SLPI) to limit the use of antibiotics and the spread of antibiotic resistance” (ISAR) under the joined supervision of Prof. S. Fillatreau, Team “Immunity in Health and Disease” at Institut Necker-Enfants Malades (INEM), and Dr. F. Mahuteau, Team “Chemistry and Modeling for Protein Recognition” at Institut Curie, and Director of the French National Chemical Library. SLPI is a protein with potent anti-microbial properties against bacteria, fungi, and viruses. It is produced by epithelial cells at mucosal barrier sites and contributes to the early defense of the organism against infections. In addition, SLPI has anti-inflammatory and tissue repair promoting functions. This unique combination of functions in a single protein makes it a particularly interesting host factor to increase host defense while limiting immunopathology. Increasing its production by the host might permit reducing the need for antibiotics, and subsequently limit the risk of the emergence of antibiotic resistance, which is becoming a major global health problem. Following this reasoning, this project will involve a screen of the national chemical library in order to identify small molecules that up-regulate SLPI expression in host cells. A hit-to-lead optimization program will be performed to improve the overall biological profile of the identified hits. This project will also examine the effect of SLPI on clinically-relevant microbial pathogen species, and assess the interaction of SLPI with antibiotics. Finally, the project will directly address how a genetically driven increased expression of SLPI in epithelial cells or neutrophils impacts on the host physiology and its resistance to microbial infections using a novel genetic mouse model.
The Institut Necker Enfants Malades (INEM) (https://www.institut-necker-enfants-malades.fr/index.php) is located on the Necker Enfants-Malades Hospital campus where it shares core facilities with the IMAGINE institute. It is in direct contact with the clinical services of the Hospital, in particular with “Bactériologie, virologie, parasitologie et hygiene service”, which is a collaborator on this project. The team of F. Mahuteau is located at Institut Curie in Orsay (https://science.curie.fr/recherche/biologie-et-chimie-des-radiations-cellulaires-et-cancer/). All the required equipment for organic synthesis, purification and analysis are available in the team.
The interdisciplinary project is funded by the CNRS through the 80|Prime program. The candidate should have an expertise in the field of chemistry (e.g. a cursus in chemistry or pharmacy) and a strong interest in immunology, in particular in host defense against infectious diseases.
Please send your application via email in English with CV and contact details of two references to both firstname.lastname@example.org and email@example.com