Our team scientific activity is committed to basic and translational research and aims at better understanding the r ole of Mononuclear Phagocytes (MNP) in inflammatory diseases and in host-virus interactions in the context of transplantation and immunodepression in order to identify new cellular and molecular therapeutic targets. We further developed new functional genomic approaches to better characterize MNP diversity and their role in immunopathology. We showed that the C-type Lectin receptor CLEC-1 acts in MNPs as an immune checkpoint during sterile inflammation (Lopez- Robles et al. Blood Adv 2017) (patent EP16306381). We now aim to study in depth the molecular mechanisms of the CLEC-1 checkpoint in mouse and human MNP in immunopathology by using functional genomics approaches. Pneumonia is currently a major cause of morbidity and mortality worldwide. To date, the most common treatments for pneumonia are antibiotics or antiviral drugs. However, these pathogen-targeted therapies fail to produce favorable results in 10-30% of patients, indicating that additional host-targeted approaches are needed to complement existing therapies. Sepsis causes inflammation and high susceptibility to nosocomial pneumonia by inducing immune defects collectively known as immunosuppression which is notably related to the emergence of myeloid suppressor cells. Our team 1 of CR2TI specialized in MNPs and immunotherapy has previously identified the CLEC-1 receptor expressed by myeloid cells, as a receptor acting as an i mmune checkpoint. Our team has hypothesized in collaboration with CR2TI team 6, specialized in the impact of inflammation on pulmonary homeostasis , that blocking CLEC-1 may help restore the functions of myeloid cells in patients with pneumonia. Thus, CLEC-1 might represent an o riginal and attractive target to prevent persistent myeloid alterations and deleterious consequences in patients with pneumonia. We propose to 1) decipher the role of CLEC-1 in myeloid cell dysfunction and immune reprogramming during pneumonia by spectral cytometry and scRNA-seq experiments, 2) study CLEC-1 blockade in pre- clinical animal models, and 3) evaluate the clinical relevance of CLEC-1 by studying pneumonia patient samples.Required Research Experiences
Biological sciences › Biology
1 - 4Offer Requirements
Biological sciences: Master Degree or equivalentSkills/Qualifications
Activity 1: The PhD will design and implement the experiments under the supervision of the principal investigators for the progression of the project,
Activity 2: - Will critically analyze the data obtained,
Activity 3: - Will generate reports, present in team or Unit meetings in English, at conferences, and will help to write potential publications
-Activity 4: - Participate in graduate school formations, interactions with undergraduate students.Specific Requirements
General, theoretical or disciplinary knowledge:
-Expertise in immunology, cell culture, cytometry, and if possible in animal experimentation in rodents and in bioinformatics for sequencing analyses.
- Fluent English, written and spoken.
- Education : MD in immunology/ with knowledge in bioinformatics will be a plus.
- Operational skills:
- Motivation, independent to advance scientific questions.
- Ethical work
- Teamwork, participation in the laboratory day of life, presentation in English at seminars .Contact Information