Air pollution consists of particulate matter (PM), inorganic gases, volatile organic compounds (VOCs), and biological materials from natural and anthropogenic sources, primarily fossil fuel combustion. Vehicle emissions contribute CO, NOx, VOCs, and nano-sized particles. Toxicological studies associate pollutants like PM and CO with neurological conditions such as dementia, implicating immunological changes in the CNS. However, limited mechanistic studies hinder intervention development. Most research on inhaled contaminants and brain inflammation relies on whole-animal models, creating a need for in vitro alternatives.
This PhD project addresses this gap using microglia and bone marrow-derived macrophage (BMDM) models. While BMDMs share functional similarities with microglia, they differ in origin1 and exhibit neuropathological roles, including brain infiltration in conditions like Alzheimer’s disease. Their dual function suggests potential support for overburdened microglia in pathological states. The project integrates new approach methodologies (NAMs) to refine regulatory toxicology by reducing reliance on genetically altered animal models. In vitro cellular models will elucidate both cellular and molecular mechanisms of inflammation induced by environmental toxins, which are increasingly been shown to contribute to negative outcomes for public health. It also aims to develop automated toxicity assessment methods, providing an ethical and scientifically relevant alternative to animal testing.
This project will fund a PhD student to investigate one cell type within the brain that is responsible for regulation responses to environmental pollution, namely microglia. The student will explore a range of environmental toxins, including CO, on these cells to monitor changes in their regulatory function with an emphasis on pro-inflammatory mediators.
