Air pollution is a major public health concern, with numerous recent reports highlighting the impact of NOx and other gases and particulate matter (PM). For decades it has been known that increased levels of PMs are associated with cardiovascular morbidity and mortality. Common sources of outdoor air pollution are combustion of fossil fuels and industrial and agricultural processes. It is well documented that exposure to air pollution cuts lives short and adversely impacts children’s development, harming their developing bodies and brains. In 2018 a new study was published which reported for the first time that the negative effects do not stop in children, but instead get worse as people age (1). There is a concern that this could make dealing with later-life brain illnesses even more expensive, and could ultimately make care for the elderly more complex for society. Indeed, the Lancet Commission on Dementia prevention, intervention and care (2) has recently identified air pollution as a modifiable risk factor for dementia, including Alzheimer’s disease (AD), the elimination of which has potential to significantly reduce disease prevalence globally.
A better understanding of the types of PMs that cause neuronal toxicity, and the mechanisms involved, could direct future policies to cut air pollution risk and identify new molecular targets for therapeutic intervention in several neurodegenerative conditions. Particulate matter, but more importantly the nanoparticle content of air pollution, have been shown to cross the blood brain barrier (BBB). Many studies have shown that nanoparticles cause neurotoxicity when they permeate the BBB, through various mechanisms including oxidative stress (3) and brain oedema (4). Given the evidence of nanoparticles causing inflammation in other sites in the body (lung and cardiovascular system), this study hypothesises that particles may be able to cause inflammation in the brain by similar mechanisms. Chronic neuroinflammation, or neuro-inflammageing, is linked to the development of several major neurological diseases, including Alzheimer’s (5) and Parkinson’s Disease (6) amongst others. If exposure to nanoparticles is shown to cause neuroinflammation there may be a link to the pathogenesis of these diseases, deepening our understanding of their epidemiology and potentially opening up new ways to treat these (and other) conditions.
As humans are exposed throughout life to a mixture of air pollutants, in vitro cell culture and in vivo animal studies are required to determine the causal effect of, and mechanism by, which different particle components of air pollution may disrupt normal cell function. This project aims to assess the impact of specific air pollution particles on clinically relevant target cells within the brain (neurons and supporting glia, including primary human astrocytes) to ascertain the effects on neurodegeneration and pro-inflammatory factors, using biochemical (ELISA), gene expression (real-time quantitative PCR), and immunofluorescence & confocal imaging techniques. Uncovering the molecular mechanisms of action connecting nanoparticle toxicity and neurodegeneration, converging on neuroinflammation, would not only direct future interventions to prevent air pollution risk but also help elucidate stronger links with increased neuroinflammation and neuronal toxicity that could impact on our understanding of neurodegeneration more widely.
A first degree (at least a 2.1) ideally in Biological/Biomedical Sciences, or related disciplines, with a good fundamental knowledge of cell biology, immunology, molecular biology and biochemistry.
English language requirement
IELTS score must be at least 6.5 (with not less than 6.0 in each of the four components). Other, equivalent qualifications will be accepted. Full details of the University’s policy are available online.
- Experience of fundamental molecular & cell biology lab skills including: cell culture, qPCR, ELISA, cell viability assays & microscopy
- Competent in research skills, data analysis and problem solving
- Knowledge of Immunology, Cell signalling, Pharmacology & Toxicology
- Good written and oral communication skills
- Strong motivation, with evidence of independent research skills relevant to the project
- Good time management
The prospective candidate should have a strong desire to undertake a lab-based research project in neuroinflammation & neurodegenerative disease and/or nanotoxicity. Experience of immunofluorescence & confocal imaging and culture of neuronal cells would be an advantage. The candidate should have the ability to work independently and as part of a multi-disciplinary team.
Please quote project code SAS0155 in your enquiry and application.
To apply for this job please visit www.findaphd.com.