The focus on particulate matter (PM2.5) mass reductions in UK air quality policy reflects the metrics measured for regulatory compliance. Epidemiological approaches have struggled to untangle the relative hazard of PM constituents within this mass, as well as co-pollutant gases, such as NO2, leading to the contention that all PM2.5 components must be treated as being equally harmful to human health. This makes little toxicological sense. The lack of a relative hazard ranking of PM constituents and co-emitted gases means that policy focuses on blunt strategies based on overall reductions in pollutant concentrations, rather than a refined focus on health relevant sources and components. This poses risks of unintended consequences, e.g. focusing on the largest contributors to PM2.5 for regulatory compliance, rather than the most harmful fractions, may fail to deliver predicted health benefits to the most vulnerable members of our society. In outdoor air this has remained unresolved for over 20-years, but further complexity is introduced by the heterogeneous indoor environment which must be considered in a complete picture of exposure. To address this major knowledge gap, the UK requires integration and focus of toxicological resource methodologies to identify the most hazardous fractions of indoor and outdoor PM and to elucidate the causal pathways contributing to disease development and exacerbation. Our proposed consortium brings together recognised UK expertise in atmospheric sciences, toxicology and biomedical sciences in a world-leading interdisciplinary collaboration to build an Air Pollution Hazard Identification Platform. This platform will deliver the capability to conduct controlled and characterised exposures to defined pollutant mixtures from different sources for in vitro, in vivo animal and human toxicological studies. We will use the large atmospheric simulation chamber at the University of Manchester to conduct experiments exposing human volunteers to diesel exhaust, woodsmoke, cooking emissions, secondary organic aerosol and NOx-enhanced mixtures, all at ambient atmospheric levels. These have been selected for their recognised substantial contributions to indoor and outdoor air pollution. The chamber exposures will be used as a reference and these experiments will be used to provide filtered samples of the PM for in vitro and transgenic animal exposures at the partner Institutions. Referenceable portable source units for all primary and secondary pollutant mixtures will be developed, characterised and deployed for in vitro and animal exposures to the full gas and particle mixture. Within the proposal, we will demonstrate the capability of the platform to elucidate the toxicological mechanisms involved in the neurological impacts of air pollution, though any health outcomes are accessible to the platform. The in vitro studies will be used to explore possible direct and indirect mechanisms for neuroinflammation and injury, identifying the molecular pathways associated with cellular activation. Using a unique panel of transgenic stress-reporter mouse lines, the stress response on exposure to the various pollutants will be tracked in a tissue and cell specific manner in vivo and provide a hazard ranking of the pollutants that can be related back to the in vitro molecular signatures. Repeat experiments with mouse lines susceptible to Alzheimer's disease will examine changes in these stress responses. Epigenetic DNA signatures will be examined in target tissues. A panel of healthy aged human subjects with a family history of increased dementia risk will provide biosamples and be subjected to cognitive tests on exposure to the different mixtures, further enabling their hazard ranking for correlation with the in vitro and animal studies. The mechanistic linkages between the animal and human exposure responses will be explored using candidate driven biomarker and untargeted metabolomic and epigenetic studies.

The COVID-19 pandemic has exposed how significant a role the indoor environment plays in the transmission of infection. The virus has highlighted how there are substantial gaps in knowledge relating to how microorganisms in aerosols and droplets are generated and dispersed in our buildings, how effectively we can measure and monitor risks in indoor environments, and how the design of the environment and the technologies within it can be used to control exposure to pathogens. While there is an immediate focus on respiratory infections, this challenge applies to a very wide range of microorganisms including gastroenteric pathogens and environmental microorganisms where exposure risks are driven by human interactions with the building layout, ventilation, heating and water systems. Understanding and tackling these challengers requires new knowledge about the interactions between microorganisms and the physical environment. Microbial aerosols in buildings are known to be released from human sources (respiratory aerosols, skin squame), building systems (aerosols from water, drainage and ventilation systems), industry processes (waste and waste water treatment, agricultural activities), the natural environment (sea, animals, plant pathogens) and medical procedures (dentistry, intubation). However we know very little about how the engineering design of the environment determines the generation, transport, deposition and control of microorganisms. Beyond microorganisms, there is growing awareness that human health is significantly affected by exposure to pollutants in indoor spaces and that many buildings are inadequately ventilated to provide healthy conditions for occupants. The CECAM (Chamber for Environmental Control of Airborne Microorganisms) facility will provide a new, multi-user research environment that can enable controlled experiments with aerosolised microorganisms under different indoor environmental conditions. The facility will enable key research questions to be addressed relating to sources and survival of microbial aerosols, methods for measuring and monitoring microbial aerosols and pollutants, the role of ventilation and room layouts on the dispersion and deposition of microbial aerosols and other pollutants, the development of effective engineering solutions including personal protective equipment, air cleaning and disinfection devices, and better designs of key components such as showers, hot air dryers, air conditioning units and drainage systems. The facility will enable research at the interfaces of fluid dynamics and aerosol sciences with microbiology and indoor air chemistry that is driven by clinical challenges and the need for improved indoor environmental quality in buildings across just about every sector of society. The CECAM facility will provide an integrated user environment that combines a controlled biocontainment chamber with dedicated air handling systems with a suite of environmental sensors and bioaerosol samplers including real-time bioaerosol sampling. Through location within a well-equipped microbiology laboratory and managed by a dedicated experimental officer, the CECAM facility will enable robust and safe experiments to be carried out by academic users, research organisations, NHS users and industry. This will include the ability for experiments to be carried out using human participants.

Aerosol science, the study of airborne particles from the nanometre to the millimetre scale, has been increasingly in the public consciousness in recent years, particularly due to the role played by aerosols in the transmission of COVID-19. Vaccines and medications for treating lung and systemic diseases can be delivered by aerosol inhalation, and aerosols are widely used in agricultural and consumer products. Aerosols are a key mediator of poor air quality and respiratory and cardiac health outcomes. Improving human health depends on insights from aerosol science on emission sources and transport, supported by standardised metrology. Similar challenges exist for understanding climate, with aerosol radiative forcing remaining uncertain. Furthermore, aerosol routes to the engineering and manufacture of new materials can provide greener, more sustainable alternatives to conventional approaches and offer routes to new high-performance materials that can sequester carbon dioxide. The physical science underpinning the diverse areas in which aerosols play a role is rarely taught at undergraduate level and the training of postgraduate research students (PGRs) has been fragmentary. This is a consequence of the challenges of fostering the intellectual agility demanded of a multidisciplinary subject in the context of any single academic discipline. To begin to address these challenges, we established the EPSRC Centre for Doctoral Training in Aerosol Science in 2019 (CDT2019). CDT2019 has trained 92 PGRs with 40% undertaking industry co-funded research projects, leveraged £7.9M from partners and universities based on an EPSRC investment of £6.9M, and broadened access to our unique training environment to over 400 partner employees and aligned students. CDT2019 revealed strong industrial and governmental demand for researchers in aerosol science. Our vision for CDT2024 is to deliver a CDT that 'meets user needs' and expands the reach and impact of our training and research in the cross-cutting EPSRC theme of Physical and Mathematical Sciences, specifically in areas where aerosol science is key. The Centre brings together an academic team from the Universities of Bristol (the hub), Bath, Birmingham, Cambridge, Hertfordshire, Manchester, Surrey and Imperial College London spanning science, engineering, medical, and health faculties. We will assemble a multidisciplinary team of supervisors with expertise in chemistry, physics, chemical and mechanical engineering, life and medical sciences, and environmental sciences, providing the broad perspective necessary to equip PGRs to address the challenges in aerosol science that fall at the boundaries between these disciplines. To meet user needs, we will devise and adopt an innovative Open CDT model. We will build on our collaboration of institutions and 80 industrial, public and third sector partners, working with affiliated academics and learned societies to widen global access to our training and catalyse transformative research, establishing the CDT as the leading global centre for excellence in aerosol science. Broadly, we will: (1) Train over 90 PGRs in the physical science of aerosols equipping 5 cohorts of graduates with the professional agility to tackle the technical challenges our partners are addressing; (2) Provide opportunities for Continuing Professional Development for partner employees, including a PhD by work-based, part-time study; (3) Deliver research for end-users through partner-funded PhDs with collaborating academics, accelerating knowledge exchange through PGR placements in partner workplaces; (4) Support the growth of an international network of partners working in aerosol science through focus meetings, conferences and training. Partners and academics will work together to deliver training to our cohorts, including in the areas of responsible innovation, entrepreneurship, policy, regulation, environmental sustainability and equality, diversity and inclusion.

An aerosol consists of solid particles or liquid droplets dispersed in a gas phase with sizes spanning from clusters of molecules (nanometres) to rain droplets (millimetres). Aerosol science is a term used to describe our understanding of the collective underlying physical science governing the properties and transformation of aerosols in a broad range of contexts, extending from drug delivery to the lungs to disease transmission, combustion and energy generation, materials processing, environmental science, and the delivery of agricultural and consumer products. Despite the commonality in the physical science core to all of these sectors, doctoral training in aerosol science has been focussed in specific contexts such as inhalation, the environment and materials. Representatives from these diverse sectors have reported that over 90% of their organisations experience difficulty in recruiting to research and technical roles requiring core expertise in aerosol science. Many of these will act as CDT partners and have co-created this bid. We will establish a CDT in Aerosol Science that, for the first time on a global stage, will provide foundational and comprehensive training for doctoral scientists in the core physical science. Not only will this bring coherence to training in aerosol science in the UK, but it will catalyse new collaborations between researchers in different disciplines. Inverting the existing training paradigm will ensure that practitioners of the future have the technical agility and confidence to move between different application contexts, leading to exciting and innovative approaches to address the technological, societal and health challenges in aerosol science. We will assemble a multidisciplinary team of supervisors from the Universities of Bristol, Bath, Cambridge, Hertfordshire, Imperial, Leeds and Manchester, with expertise spanning chemistry, physics, biological sciences, chemical and mechanical engineering, life and medical sciences, pharmacy and pharmacology, and earth and environmental sciences. Such breadth is crucial to provide the broad perspective on aerosol science central to developing researchers able to address the challenges that fall at the boundaries between these disciplines. We will engage with partners from across the industrial, governmental and public sectors, and with the Aerosol Society of the UK and Ireland, to deliver a legacy of training packages and an online training portal for future practitioners. With partners, we have defined the key research competencies in aerosol science necessary for their employees. Partners will provide support through skills-training placements, co-sponsored studentships, and contribution to taught elements. 5 cohorts of 16 doctoral students will follow a period of intensive training in the core concepts of aerosol science with training placements in complementary application areas and with partners. In subsequent years we will continue to build the activity of the cohort through summer schools, workshops and conferences hosted by the Aerosol Society, virtual training and enhanced training activities, and student-led initiatives. The students will acquire a perspective of aerosol science that stretches beyond the artificial boundaries of traditional disciplines, seeing the commonalities in core physical science. A cohort-based approach will provide a national focal point for training, acting as a catalyst to assemble a multi-disciplinary team with the breadth of research activity to provide opportunities for students to undertake research in complementary areas of aerosol science, and a mechanism for delivering the broad academic ingredients necessary for core training in aerosol science. A network of highly-skilled doctoral practitioners in aerosol science will result, capable of addressing the biggest problems and ethical dilemmas of our age, such as healthy ageing, sustainable and safe consumer products, and climate geoengineering.