O'Garra lab Immunoregulation and Infection Laboratory

Heatmap showing gene activity increasing and decreasing over time in mice infected with the bacterium that causes tuberculosis.

Our laboratory focuses on the study of the regulation of the immune response during immune challenge and infection, to identify immune cells, pathways and targets of protection and pathogenesis determining disease outcome.

Our immune systems use many mechanisms to protect us from infection. These include messenger molecules called cytokines which help to direct immune cells to eradicate pathogens, an area of research which my laboratory has focused on for many years.

Immune cells can produce different cytokines in response to infection, but uncontrolled responses can damage healthy cells and cause inflammation and disease, during infection with pathogens and pathobionts. Our goal is to understand the mechanisms regulating the immune response to control infection with pathogens and pathobionts while minimising damage to the host.

Collectively, the aims of the lab are to identify immune cells and pathways contributing to:

  1. the regulation of cytokine-driven pathways in myeloid cells and T cells leading to or controlling pathology in models of infection or challenge of the peritoneal cavity and the gut, including during infection with H. hepaticus, T. gondii and E. coli.
  2. the mechanisms in the lungs which determine disease outcome using:
    • M. tuberculosis infected tuberculosis (TB) resistant and susceptible mice where the blood transcriptomic RNA signature resembles human TB disease
    • airway samples from human TB patients and their contacts most of whom will control the infection while others will progress to TB.

A unifying theme of the lab is the study of cellular and gene expression changes in the mucosal sites, specifically now focussing on the lung and airways (TB) and the gut and periphery (H. hepaticus, T. gondii and E. coli) to define immune cells, cytokines, and new targets, contributing to health or disease. Our approaches range from complex flow cytometry and histology to genomics technologies including RNA-Sequencing, single-cell RNA-sequencing and ATAC-sequencing. Targets/pathways identified are then tested to identify their role in protection, chronic infection and/or immunopathology.

In addition to postdoctoral fellows, PhD students, computational biologists and lab research scientists, the lab is complemented by clinician scientists, either as visiting scientists or clinical collaborators, who play an important role in the lab projects, from providing samples to the development of approaches for molecular study of the immune response in human disease.