In vitro modelling of lung response to environmental nanoparticulates

Nanotechnologies over the last few decades have gained huge attention and are estimated to continue growing, worth approximately $1 trillion by 2025. Nanoparticles (NPs) are produced by nanotechnologies and are on the rise in many consumer products, leading to a growing number of concerns for potential health effects with inhaled airborne exposure. This has led many studies to investigate inhaled NP toxicity, showing association with premature mortality and lung diseases as well as cardiovascular disease. Toxicity can be contributed to by many factors including composition, size, and shape, but also with pro-inflammatory effects, cellular oxidative stress, and lung clearance/retention. NPs potential health hazards with both indoor and outdoor sources, need to be answered due to growing concerns of the public, politicians and scientists. Nanotoxicology is employed to investigate the magnitude and mechanism of NP effect. Typically, animal studies have been used when investigating inhalable particulate matter toxicology, however, it is costly, time-consuming, and most importantly does not provide a good representation of the human lung's response, leading to the safety assessment being inaccurate. Alternatives have been used with in-vitro, human lung cells, solving the costly and time-consuming aspects of the limitations of animal models, however, they're usually one type of cell, not accurately representing the complex nature of the interactions within the lung. To address the limitations found in both, an in-house developed in-vitro model for alveolar epithelium and immune cells, exposure chamber ALI models, in conjunction with toxicological assays, expression studies and high content analysis will be used. Culminating in a more detailed understanding of the toxicological profile of the NPs.

Aerosol science has a significant impact on a broad range of disciplines, extending from inhaled drug delivery, to combustion science and its health impacts, aerosol assisted routes to materials, climate change, and the delivery of agricultural and consumer products. Estimates of the global aerosol market size suggest it will reach $84 billion/year by 2024 with products in the personal care, household, automotive, food, paints and medical sectors. Air pollution leads to an estimated 30-40,000 premature deaths each year in the UK, and aerosols transmit human and animal infections. More than 12 million people in the UK live with lung disease such as asthma, and the NHS spends ~£5 billion/year on respiratory therapies. Many of the technological, societal and health challenges central to these areas rely on core skills and knowledge of aerosol science. Despite this, an Industrial Workshop and online survey (held in preparation for this bid) highlighted the current doctoral skills gap in aerosol science in the UK. Participating industries reported that only 15% of their employees working with aerosol science at doctoral-level having received any formal training. A CDT in aerosol science, CAS, will fill this skills gap, impacting on all areas of science where core training in aerosol science is crucial.

Impact on the UK aerosol community: Aerosol scientists work across governmental policy, industrial research and innovation, and in academia. Despite the considerable overlap in training needs for researchers working in these diverse sectors, current doctoral training in aerosol science is fragmentary and ad hoc (e.g. the annual Fundamentals of Aerosol Science course delivered by the Aerosol Society). In addition, training occurs within the context of individual disciplines, reinforcing artificial subject boundaries. CAS will bring coherence to training in the core physical and engineering science of aerosols, catalysing new synergies in research, and providing a focal point for training a multidisciplinary community of researchers. Working with the Aerosol Society, we will establish a legacy by providing training resources for future researchers through an online training portal.

Impact on industry and public-sector partners: 45 organisations have indicated they will act as CAS partners with interests in respiratory therapies, public health, materials manufacturing, consumer and agricultural products, instrumentation, emissions and environment. Establishing CAS will deliver researchers with the necessary skills to ensure the UK establishes and sustains a scientific and technical lead in their sectors. Further, it will provide an ideal mechanism for delivering Continuing Professional Development for the existing workforce practitioners. The activity of CAS is aligned to the Industrial Strategy Challenge Fund (e.g. through developing new healthcare technologies and new materials) and the EPSRC Prosperity Outcomes of a productive, healthy (e.g. novel treatments for respiratory disease) and resilient (e.g. adaptations to climate change, air quality) nation, with both the skilled researchers and their science naturally translating to long-lasting impact. Additionally, rigorous training in responsible innovation and ethical standards will lead to aerosol researchers able to contribute to developing: regulatory standards for medicines; policy on air quality and climate geoengineering; and regulations on manufactured nano-materials.

Public engagement: CAS will provide a focal point for engaging the public on topics in aerosol science that affect our daily lives (consumer products, materials) through to our health (inhalation therapeutics, disease transmission and impacts of pollution) and the future of our planet (geoengineering). Supported by a rigorous doctoral level training in aerosol science, this next generation of researchers will be ideally positioned to lead debates on all of these societal and technological challenges.