Understanding how pollutant aerosol particulates impact airway inflammation

Exposure to particulate matter (PM) contributes to respiratory diseases with major impacts from early life exposure yet we know little of the underlying immunological mechanisms. Increasing evidence implicates a process of "innate imprinting" whereby prior inflammation alters subsequent responses and increases inflammation. This is particularly problematic for infant development and subsequent responses to infection and allergy. This project will develop a range of particulates in order to explore the cellular response to PM aerosols and innate imprinting in airway inflammation.

This proposal will combine bioinformatics analysis with in vitro and in vivo methods to define the cellular response to PM.
Aim 1: Development of a well-characterized simulated environmental particulate panel including diesel combustion particles (available through partner) and of a selection of particles already used in the labs.
-Physical-chemical properties of particulates will be characterised prior to and after mixing with simulated lung fluid and in exposure-relevant conditions in order to characterise particulate and inform accurate dose representation in the subsequent stages of the PhD project
Aim 2: Assess epithelial and macrophage responses to primary and secondary stimulation with simulated environmental particulate panel.
-This will be achieved by assessing association and uptake of particulate to cells (TEM, light microscopy), cell viability, and production of immune effectors by qPCR, cytometry etc and examination of differential pathways of cell damage/activation/response.
Aim 3: To examine early life in vivo responses to aerosol pollutants within the lung.
-The first stages of life are a critical time for development of the immune system and are highly sensitive to environmental exposures. Neonatal mouse lungs will be exposed to PM of different properties and examined for inflammatory responses to biological aerosols in later life. Inflammatory and toxicological effects including innate memory will be assessed using flow cytometric, histochemical and mRNA sequencing among other methods. This will largely be done in the partner institution.



This project is part of the EPSRC CDT in aerosol science and the student will get training in core aerosol science background, research methods, programming skills, as well as professionalism and knowledge translation, while developing their PhD research proposals. Students will also have access to an online training portal where they can listen to mini lectures and solve multiple choice problems. They will also attend in class training solving more complex research problems underpinned by the science they have learned during the course of their training.