Loxham - BBSRC - Future Leaders Fellowship - Cellular Responses to Shipping-Related Particulate Matter (May 16)

Outdoor air pollution kills over 3 million people worldwide every year, and 40,000 per year in the UK alone, taking 6 months off the life of the average person. In order to improve our chances of ageing healthily, we need to understand better how air pollution exerts its damaging effects. The component of air pollution most strongly linked to ill-health and death is airborne dust, also known as particulate matter (PM) which is invisible to the naked eye. This PM comes from a variety of sources, such as vehicle exhaust, combustion, erosion of soil by the wind, and sea spray. In turn, the composition of the particles, their size, and shape, depends on where they come from. PM deposits on the cells which line our airways and the air sacs in our lungs, called epithelial cells, and can then affect their functioning. Moreover, PM may potentially enter the cells and cross into the bloodstream. PM can cause sore throat, itchy eyes, cough, and wheezing, but has also been linked to asthma, heart attacks, stroke, and lung cancer. The source and chemical composition of PM is thought to be important in understanding the effects of PM, and therefore we need to investigate a range of sources of PM. One such source is shipping and associated activities. Emissions from ships are thought to kill 60-70,000 people per year worldwide. In addition to ship emissions, dock areas are associated with heavy goods vehicles carrying freight, oil refining, and scrap metal handling. Therefore, there are a number of potential sources of PM, with research needed to understand their differing effects. This study will involve the collection of airborne PM from a number of different sites across Southampton docks. I will analyse the elements and molecules which make up the PM, with special attention to the levels of metals and carbon-based molecules, both of which have been linked to especially damaging effects. Following this, two models to represent the airways will be constructed in the laboratory. Firstly, epithelial cells from the tubes which carry air into the lungs will be grown and exposed to the PM, using different amounts of PM and exposing the cells for different lengths of time. The release of molecules indicating inflammation will be measured, as will the death of cells as a result of PM exposure. Secondly, epithelial cells which line the air sacs in the lungs, and form the surface across which oxygen enters the blood from the lungs, will be grown in close proximity to the cells which line the blood vessels of the lungs (endothelial cells). A high-powered microscope called an electron microscope will be used to assess the extent to which the particles enter the epithelial and endothelial cells, or the gaps between the cells. This will indicate whether the airborne PM might have the ability to enter the bloodstream. In each case, differences in the responses of cells to the PM will be related to the different sources and composition of the particles. Finally, epithelial cells brushed from the airways of volunteers and then grown in the laboratory will be exposed to PM, and changes in levels of molecules called RNAs will be measured. These RNAs represent the cell taking information from its DNA, and converting it to a more useable form, so by measuring millions of RNA molecules in the cells, we can get a much better idea of exactly how the cell is responding to PM. This process can give us excellent insight into the mechanisms of these responses, and might shed new light on changes which occur after we inhale PM. Again, the changes will be related to the different types of PM. We hope that in the future, we might be able to use these changes as markers to identify people at risk of the effects of PM. The overall results of the project will give us valuable new information about the different sources of PM around dock areas, the PM composition, and which PM sources might present the greatest risk to our chances of ageing healthily.