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Role of alveolar macrophages in Covid19 pathology

Sir William Dunn School of Pathology

Prof W S James , Dr S Cowley Friday, January 08, 2021 Competition Funded PhD Project (Students Worldwide)

About the Project

For most people infected with SARS-CoV-2, infection appears to be only mildly symptomatic, transient and limited to the upper airways and epithelia of the nasopharynx. However, more serious disease involves the alveolar cells of the lung, including Type 2 pneumocytes and alveolar macrophages, resulting in pneumonitis, infiltration by blood monocytes, endothelial leakage, intravascular coagulation and disseminated pathology in multiple organs. A critical step from mild to severe disease appears to be the replication of the virus in the alveolar cells, and it is unclear to what extent in vivo the resident macrophages protect the pneumocytes from infection, on the one hand, or promote deleterious inflammatory reactions to infection, on the other. Understanding how the molecular cell biology of macrophages regulates this balance between defence and disease is critical to rational approaches to combat Covid19 disease, and has implications for other lung infections. To address these questions, we have developed a genetically tractable, yet pathophysiologically authentic human alveolar tissue-in-a-dish model using induced pluripotent stem cell differentiation to generate both macrophages and type 2 pneumocytes in coculture. You will work with other members of the James Lab, particularly with Dr Sally Cowley, Head of the James Martin Stem Cell Centre, to investigate the involvement of specific pathways of macrophage sensing and response in relation to SARS-CoV-2 infection. You will be trained in Containment Level 3 techniques for safe working with SARS-CoV-2, and in techniques of stem cell mutagenesis and differentiation.

Funding Notes

4 Year DPhil Prize Studentships cover full University fees, a tax free enhanced stipend of ~£17,285 pa, and up to £5,300 pa for research costs and travel. The competition is open to applicants from all countries. See View Website for full details and to apply.


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