Project Outline

As we age our risk of respiratory infections increases. While research into inflammageing has advanced our understanding of the role the immune system plays, the field of ageing research has failed to consider the impacts of the ageing lung microbiome on disease risk. In mice, advanced age is linked to impaired alveolar macrophage phagocytosis, antiviral responses, and TLR signalling (27357201), with human macrophage function understudied.

Our model of the human-ageing lung microbiome combines human macrophages, which are key phagocytic cells of the lung, with bacterial isolates from older people. Data thus far has shown impaired phagocytosis (Figure 1A) and bacterial killing (Figure 1B) of respiratory bacteria Haemophilus influenzae by macrophages isolated from older adults compared to young adults. We have advanced this assay to incorporate multiple pathogenic and commensal bacteria, to create a mock lung microbiome.

Anti-ageing drugs, affect innate immunity and have the potential to alter the lung microbiome, and are either repurposed antibiotics (rapamycin) or have demonstrated impacts on infection risks (resveratrol and metformin).

In this PhD project the postgraduate researcher will be using phagocytosis assays, microbiology and molecular biology to understand whether we can manipulate the interaction between macrophages and bacteria using anti-ageing therapies, or by other means.

Techniques

Bacterial and human tissue culture, phagocytosis and killing assays, flow cytometry, confocal microscopy, DNA sequencing and molecular microbiome techniques