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