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Reference : UMR5089-EMMLEF-001
Workplace : TOULOUSE
Date of publication : Wednesday, April 21, 2021
Scientific Responsible name : Lefrançais Emma
Type of Contract : PhD Student contract / Thesis offer
Contract Period : 36 months
Start date of the thesis : 4 October 2021
Proportion of work : Full time
Remuneration : 2 135,00 € gross monthly
Description of the thesis topic
We have recently demonstrated that extramedullar thrombopoiesis occurs in the lung but the specificities, regulation and significance of this local production is unknown. Recent studies and our preliminary data suggest that lung megakaryocytes have a specific role in inflammation and that platelet biology are altered during lung damage by local inflammatory mediators, including by the tissue alarmins.
This PhD project aims at studying lung thrombopoieisis regulation and specificities and evaluate the impact of lung platelet modifications on hyper inflammation and remodeling. The project integrates the use of murine models of lung inflammation, flow cytometry, proteomic analysis and cutting edge lung intravital microscopy. The overall goal is to bring a deeper understanding of lung inflammatory diseases where platelets are known to contribute to dysregulated inflammation (ARDS, asthma, COPD, viral infection…) and will support the discovery of new therapeutic targets.
The project will be advised by Emma Lefrançais in the lab of Jean-Philippe Girard
• Lefrançais E et al. The lung is a site of platelet biogenesis and a reservoir for megakaryocytes and hematopoietic progenitors. Nature 2017
• Lefrançais E and Looney M "Platelet biogenesis in lung circulation" Physiology 2019. 34 (6) 392-401
• Cayrol C et al Environmental allergens induce allergic inflammation through proteolytic maturation of IL-33 Nature Immunology 2018
• Cayrol C, Girard JP. Interleukin-33 (IL-33): A nuclear cytokine from the IL-1 family. Immunol Rev. 2018
• Liew FY, Girard JP, Turnquist HR. Interleukin-33 in health and disease. Nature Reviews Immunology 2016
• Lefrançais E et al. The central domain of IL-33 is cleaved by mast cell proteases for potent activation of group 2 innate lymphoid cells. PNAS 2014
The IPBS is a joint research center of the CNRS and the University of Toulouse in the heart of the main campus of the University of Toulouse III-Paul Sabatier, which offers high-level multidisciplinary training in the fields of science, health and engineering. The IPBS currently hosts more than 230 scientific and administrative staff, including more than 40 PhD students and post-doctoral fellows of multiple nationalities. The IPBS currently comprises 15 research groups working in the fields of inflammation, infection and cancer, as well as 4 state-of-the-art technological facilities in proteomics, biophysics and structural biology, molecular and cellular imaging, and functional exploration, including in several BSL-3 laboratories for the study of infectious diseases such as tuberculosis and other pulmonary and enteric infections, and more recently COVID-19.
We are looking for:
- creative and highly motivated Ph.D. students of all nationalities strongly committed to research
- applicants must have an excellent M.Sc. or equivalent degree with a strong background in immunology and/or physiopathology
- Experience in flow cytometry and in vivo models will be a plus.
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