In the last few decades China's rising energy requirements have led to increased air pollution emissions from coal-fired power plants. Its motorized transport growth is the fastest in the world with the number of motor vehicles projected to quadruple in the next two decades, reaching over 380 million by 2030. Meanwhile, nearly half of all Chinese still cook and heat their homes with highly polluting biomass and coal fuels. The resulting particulate matter (PM) concentrations in the majority of Chinese cities routinely exceed the World Health Organization's (WHO) annual Air Quality Guideline of 10 microgrammes/m3 by a factor of 10 or more. Epidemiologic studies undertaken in China increasingly confirm links between poor air quality and a range of health risks previously observed in the West. Moreover, they confirm that the number of Chinese that are vulnerable to air pollution is increasing, as evidenced by a large and growing burden of disease from chronic non-communicable diseases - such as ischemic heart disease (IHD), cerebrovascular disease, chronic obstructive pulmonary disease (COPD), and cancer. Research to enhance the understanding of the impact of environmental exposures on human health is needed to influence both government policy on pollution and also individual behaviours. The outcomes of the research described in this proposal will extend our understanding of the impact of air pollution on human health to a megacity in the world's largest country and promote evidence-based policies that in turn may greatly improve the health and quality of life of China's ageing population - both of which are important sustainable development aims. Working closely with Chinese scientists we will recruit a panel of 240 subjects from urban and peri-urban Beijing. Subjects will be recruited from two existing populations cohorts (PRC-USA and INTERMAP) ensuring a rich source of baseline data and stored samples for access. Across the project period we will obtain detailed information on the current health status of the subjects, details of the personal exposure to air pollution and biosamples for biomarker analysis. The UK has been at the heart of the scientific study of air pollution issues over many decades, whereas such scientific studies are much newer in China. Although the Chinese teams have developed a high level of expertise in some areas, the UK team will provide strong complementary expertise, in particular in personal exposure air pollution measurements and biomarker analysis. Inherent throughout however is the synergistic combination of Chinese expertise and capability, complementary UK air quality instrumentation and health expertise. Therefore, this project will serve as a new platform to further enhance the research capacity of the Chinese teams in air pollution and its impact on health, which will leave a legacy beyond the project lifetime, thus contributing to the continuous improvement of life and welfare of more than a billion people.

Large cities in China, including the capital city of Beijing, and their surrounding areas have some of the highest air pollution levels in the world. With over one half of China's population now living in cities, air pollution and air quality are important local and national policy issues. At the same time, China is undergoing changes in health: Deaths in children have come down impressively, and people live to older ages when diseases of the heart and the lung are more common and important. Air pollution in cities is one of the main causes of health problems and disease in China, with especially large effects on the heart and the lung. We know from research in Europe and North America that air pollution adversely affects human health, but we know little about how and why this happens, and whether air pollution from different sources has more or less effects. Even less is known about what these mechanisms are in China, where air pollution may be from different sources and therefore have different chemistry. This knowledge is important for deciding what the most effective strategies to reduce the health effects of air pollution are. In this research project, leading scientists from China and the United Kingdom will work closely to use modern methods in epidemiology and biological sciences to better understand which components of air pollution affects human health in China, and how these effects occur. This knowledge will be used together with information from our related research projects to identify the most effective ways of protecting human health from air pollution in Chinese cities.

The neurotransmitter dopamine, in the brain region called the striatum, is vitally important for our everyday actions and motivations. Without dopamine we develop Parkinson's disease and cannot move, but with too much dopamine, we develop addictions. If we could understand more about how dopamine is controlled by the brain, we might better understand how the brain regulates these behaviours, and how we might treat them better in disease. This project builds on a newly emerging area of neuroscience research that is transforming our understanding of the way brain circuits are regulated. In particular, new research suggests that neurons in the brain can be controlled by non-neuronal cells called astrocytes. In this project, we will explore whether astrocytes might control dopamine function. This is an area of biology which has been completely overlooked until now. Astrocytes vastly outnumber neurons in the brain and have long been known to be important for generally maintaining the brain and its supply of nutrients. Our current understanding of astrocyte function in brain circuits lags significantly behind our understanding of neuronal function but is now beginning to grow rapidly thanks to the advent of new experimental tools to modulate astrocyte activity. Recent work with these new tools demonstrates that astrocytes have more roles than once believed, and that strikingly, they can play powerful roles in directly regulating neurotransmitter release. In this project, we will examine for the first time, the fundamentally important questions of whether astrocytes in the striatum can modulate dopamine release and function. Until now, no-one has established whether or not astrocytes play a role in regulating dopamine release in the striatum. We have some new data which strongly suggest that astrocytes play an important role. Our first main aims will be to establish whether astrocytes in striatum dynamically modulate dopamine release, the mechanisms through which they might do it, and whether this impacts on dopamine-dependent behaviours. We will use state-of-the art tools, called chemogenetics and optogenetics, to specifically modulate the activity of astrocytes in mouse brains to understand their impact on dopamine function. Our second main aim will be to understand better whether there are changes to the biology of astrocytes in the striatum in Parkinson's disease. Astrocytes have been implicated as playing a role in Parkinson's disease, as well as in other neurodegenerative diseases, in which they can lose their supportive roles and gain neurotoxic properties. We have some new data which suggest that there are changes to the way that astrocytes work in striatum in Parkinson's disease and that might have negative consequences for dopamine function in the striatum. In this project, we will develop a better understanding of how astrocytes change in humans as well as in animal models, and test whether and how this impacts negatively on dopamine function in Parkinson's disease. Overall we expect this new and original project to greatly increase fundamental knowledge about how astrocytes control brain function in health and disease. It should cause a big shift in thinking. We expect to find that astrocytes are key players in governing dopamine function and that there are disruptions to the way that astrocytes operate and control dopamine function in Parkinson's disease. This work could also open up potential new avenues for drug discovery, by identifying disruptions to astrocyte biology that could be targets for future treatments for Parkinson's disease and other dopamine-related disorders.

The aftermath of explosive volcanism is ecologically important in Indonesia but difficult to study because of its unpredictability. In this proposal, we propose to monitor ecosystem recovery after volcanic eruptions with a specific focus on soil micro-organisms and how they can mediate initial soil development in fresh ash deposits. Whilst previous studies have examined microbial communities in 'young' volcanic environments, the age of these deposits was generally in the order of years, thereby missing the key earliest stages of succession during which microbes start to modify the initial edaphic environment. Major volcanic activity at Anak Krakatau, an iconic island volcano in Indonesia, in December 2018 led to a complete reconfiguration of the island and the rare opportunity to study microbial recolonisation and the importance of microbes in ecosystem recovery. In this urgency project, we will sample ash/soils from Anak Krakatau within a few months of the eruption producing a novel dataset. Microbial diversity will be compared with that in the spore-rain to assess if there are constraints to microbial colonisation. We will also set up a series of experiments whereby we inoculate ash/soil to determine how the colonisation of microbes can influence carbon and nutrient accumulation in the ash substrate and the growth of pioneer plant species, and conversely how constraints to colonisation might impede it. Understanding the development of soils over volcanic ash is important because they are very fertile and support high population densities as well as sequestering large amounts of carbon over decadal timescales.

Silicon Photonics is currently transforming data communications, and beginning to impact longer reach applications. However, Silicon Photonics is now maturing and current commercially available transceivers mainly utilise modulators operating at 25Gb/s. Laboratory demonstrators for next generation systems either use multiple parallel lanes of 25Gb/s devices, or perhaps more complex modulation techniques to achieve higher aggregate data rates. Even the fastest research modulators, when integrated with drivers, operate up to approximately 50Gb/s OOK (or corresponding PAM4 modulation to reach a net aggregate speed of 100Gb/s). Researchers worldwide are trying to improve such modulators to squeeze the last few percentage points of improved performance out of these devices, or are turning to integration of other materials, which increases fabrication complexity and cost, and potentially reduces yield. In this work we have invented a way to improve the modulator/driver combination not by a few percent, but by 100%, which will lead to dramatic improvements in data rate, power consumption, and cost of implementation. We will demonstrate 100Gb/s OOK and 200Gb/s PAM4, as well as a novel Optical Time Division Multiplexing (OTDM) system. In effect, we have found a way to transfer functions that were traditionally done in the electronic domain, to the optical domain, saving cost and energy and dramatically improving performance. The proposal provides detailed simulations of the proposed work as preparatory demonstration of the viability of the new techniques. This includes typical characteristics of modulators previously fabricated at the Southampton, which will now be operated in a different mode. Consequently, we are confident that the chances of success are very high. Electronic drivers will be designed at Southampton and subcontracted to TSMC in Taiwan for fabrication. All optical devices will be fabricated at Southampton using the Silicon Photonics Foundry service called CORNERSTONE. The new approach has already led to 2 patent applications, and we suspect others will follow as we progress with the research. Both investigators and the research investigator are inventors, so the team is ideally placed to carry out the work.