"Studying the role of lung resident myeloid cells in the response to radiation (2022-09-LONDONO_FOUILLADE)" project details

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General information

Application closed

2022-09-LONDONO_FOUILLADE

Lung fibrosis; Myeloid cells; Single cell analyses; Spatial transcriptomics; Cell-cell interaction

Studying the role of lung resident myeloid cells in the response to radiation

Director(s) and team

Arturo LondoƱo-Vallejo & Charles Fouillade

Telomeres and Cancer

Abstract

The team has been working on radiation-induced pulmonary fibrosis for several years and has introduced state-of-the-art technologies such as single cell (sc) RNAseq and single molecule (sm) FISH to the study of the cellular and molecular mechanisms that lead to failure in the regeneration response of the irradiated lung. We use a well characterized mouse model, have sequenced almost half a million lung cells and collected data corresponding to several time points after irradiation under conditions that lead (or not, as a control) to irreversible lung fibrosis. We have also access to human specimens of irradiated lungs, which should allow us to facilitate results extrapolations. Our data has revealed previously unrecognized events affecting capillary endothelial cells. We have also data pointing to fibrosis-specific response involving resident macrophage cells. Specifically, transcriptional signatures can be detected involving both inflammatory and anti-inflammatory pathways, as well as the implication of ligand production that potentially target other cell types.   In this project, we will use available genetically modified mice to determine the role of lung resident myeloid populations in response to radiation.  
  We propose to: i)                    characterise, by scRNAseq analysis, the molecular alterations induced by radiation in the different subsets of lung myeloid cells ii)                   map, by smFISH-based spatial transcriptomic approaches, interesting subsets of lung macrophages or dendritic cells that may play a role in the development of radiation-induced pulmonary fibrosis iii)                 select, from the scRNAseq data, putative interactions between resident myeloid cells and other lung cell types that will be validated by in vitro functional assays.

Requirements to apply for the PhD thesis project

The team has been working on radiation-induced pulmonary fibrosis for several years and has introduced state-of-the-art technologies such as single cell (sc) RNAseq and single molecule (sm) FISH to the study of the cellular and molecular mechanisms that lead to failure in the regeneration response of the irradiated lung. We use a well characterized mouse model, have sequenced almost half a million lung cells and collected data corresponding to several time points after irradiation under conditions that lead (or not, as a control) to irreversible lung fibrosis. We have also access to human specimens of irradiated lungs, which should allow us to facilitate results extrapolations. Our data has revealed previously unrecognized events affecting capillary endothelial cells. We have also data pointing to fibrosis-specific response involving resident macrophage cells. Specifically, transcriptional signatures can be detected involving both inflammatory and anti-inflammatory pathways, as well as the implication of ligand production that potentially target other cell types.   In this project, we will use available genetically modified mice to determine the role of lung resident myeloid populations in response to radiation.  
  We propose to: i)                    characterise, by scRNAseq analysis, the molecular alterations induced by radiation in the different subsets of lung myeloid cells ii)                   map, by smFISH-based spatial transcriptomic approaches, interesting subsets of lung macrophages or dendritic cells that may play a role in the development of radiation-induced pulmonary fibrosis iii)                 select, from the scRNAseq data, putative interactions between resident myeloid cells and other lung cell types that will be validated by in vitro functional assays.