A multi-disciplinary study into air pollution-associated transition metal homeostasis in the lungs.

Particulate matter (PM) air pollution, which comes from a wide range of sources, is a leading risk factor for ill health. However, our understanding of effects on the lung of different components of PM, which relate to PM source, is poor. This is important in understanding why some types of PM may be more toxic than others. We are especially interested in how metals in PM may drive development and exacerbation of lung diseases such as idiopathic pulmonary fibrosis. Recent work in our group has shown that ultrafine PM (the smallest size fraction of PM) associated with shipping is enriched in vanadium and nickel, and that this PM, as well as vanadium and nickel alone, exerts multiple effects on exposed cells. We have also observed effects associated with other transition metals in particles from different sources, such as underground railways. We are now keen to understand how PM metals accumulate within cells, how cells maintain homeostasis of intracellular metals (the metallome), and the consequences if this fails.
In this multidisciplinary project, we will study how transition metals, focusing initially on vanadium and nickel, may differentially accumulate within, and affect, the epithelial cells which line the alveoli, evaluating the roles played by metal transporting/binding proteins. The key aims are:
1. investigate modulation of metal transporters and metal binding-proteins in response to vanadium and nickel exposure
2. investigate accumulation of vanadium and nickel in exposed cells, and effects on the homeostasis of other metals, using state-of-the-art mass spectrometry techniques
3. investigate the mechanisms through which the observed effects occur, and the consequences of their dysfunction, using pharmacological and/or genetic techniques.
The results of this project will expand our understanding of how cells respond to different metal components of airborne PM, and how PM from different sources may be important in driving lung disease.