Chemical Genomics of Intracellular Mycobacteria (CGIM)
Priscille Brodin created the CGIM team in 2011, when she was appointed to the Center for Infection and Immunity (CIIL). Formerly, Priscille Brodin headed an Inserm Avenir team at the Institut Pasteur Korea. Priscille Brodin was awarded the SANOFI Pasteur Junior Award in 2014.
The team’s premises are located at the Institut de Biologie de Lille-CNRS for offices, benches, BSL-2 labs and 700 Terabytes servers as well as at the Institut Pasteur de Lille for the BSL-3, the high content screening (HCS) platform and animal facilities comprising breeding possibilities of different models in the context of category 3 agent infections. The majority of the CGIM equipment was acquired during the installation phase (ERC-STG Grant, the PIA ImaginEx BioMed and CPER Grant). In addition to a basic institutional grant from the CIIL (25,000 € /year), the PI of the group is also an EMBO Young Investigator (2016-2019; 15,000 €, mission and training support), coordinator of an ANR grant (AT2R-Traak-Bioanalgesics ANR- ANR-17-CE18-0001), a grant from the Institut Pasteur of Lille (Criblage antidouleur) and a grant from I-SITE UNLE (ERC-Generator). The team is partner of different ANR grants (TB-MET ANR-14-CE14-0024, ANTI-TB-NANO ANR-14-CE08-0017, TB-Emerg ANR-16-CE35-0009) and a joined project of Institut Pasteur PTR22-16. Since the last Hceres evaluation in 2013, 11 researchers, 8 research assistants and 7 Master or PhD students joined the CGIM team.
Mycobacteria are the etiological agents of three major diseases in humans: Tuberculosis caused by Mycobacterium tuberculosis, Leprosy caused by M. leprae and Buruli ulcer caused by M. ulcerans. Each year, tuberculosis results in millions of death and pulmonary cases, while Buruli ulcer, a severe skin disease, afflicts thousands of children in endemic areas such as Africa and south east Asia. Both M. tuberculosis and M. ulcerans have strong interactions with the host cells to allow their successful establishment in the host and causing disease. Our research vision is focused on investigating the molecular and cellular signalling pathways targeted by the major virulence factors encoded by these two pathogenic mycobacteria.
Chemical biology on the Mtb/macrophage model. Identifying host cell targets for antimycobacterial therapy is an expanding, promising but also very competitive field. The CGIM team found a specific and fruitful niche in the field of high-content screening and high-throughput imaging systems to study host-pathogen interactions, and is clearly recognized as one of the leaders in the field.
Identification of novel pathways involved in host-microbe interactions. We also use visual high throughput screening of drugs, siRNA, miRNA and microbial mutants to search for new host and microbial targets through collaborations (EquipEx ImagInEx BioMed) and for the team’s main research objectives.
TB Drug discovery. The team has also been involved in long lasting drug discovery projects including 1) assay design, 2) identification of hits from high-throughput 50k size library screening, 3) lead optimization, 4) early ADMET and nanoparticle delivery and 5) in vivo efficacy in tuberculosis models of infection. These studies were supported by different EU-FP7 projects (MM4TB, CycloNHIT) and an ANR project (ANTI-TB-NANO) and rewarded by the SANOFI Junior Prize in 2014.