Use of force by law enforcement officials, including police and correctional officers, is a highly important issue. Yet whilst the situations in which these officials use firearms, and the effects of this use, are relatively well documented and understood, this is not the case with 'less lethal' weapons and 'less lethal' force. (For the purposes of this project, less lethal force, or LLF, includes the use of restraints, empty hand techniques and less lethal weapons. The latter are weapons, such as the electric-shock Taser, pepper spray or batons, intended to subdue or incapacitate rather than cause serious harm or death). There is a recognition amongst academics and practitioners alike that this needs to change. Internationally, the current UN Special Rapporteur on Extrajudicial, Summary and Arbitrary Executions has expressed the need for more research into LLF, as has the UN Subcommittee for the Prevention of Torture. Nationally, a recent article in Forensic Science and Medical Pathology called for research into, and better reporting of, less lethal force in the UK, as did the Experts' Meeting on Taser the PI convened in 2015 with ESRC funds. The National Police Chief's Council (NPCC) and College of Policing have stressed the pressing need for research into LLF, and the Home Secretary has called for more information on police use of less lethal force and has launched a review into Use of Force Reporting (the 'Reporting Review'). At least three key topics around less lethal weapons remain under-researched, and this project will tackle all three directly. First we lack a basic understanding of when, why, on whom, and how often, less lethal weapons are used - and whether certain groups of people (those of a particular gender, ethnic minority, mental health status or geographical origin) are more or less likely to have less lethal force used on them. This project will see the PI work closely with the National Police Chief's Council, the Home Office and UK police forces, utilizing datasets previously unavailable to academic researchers to answer such questions. Such issues are also relevant internationally, as shown by recent debates on police less lethal force in countries as varied as Armenia, Hungary and New Zealand. Second, whilst these weapons are associated with saving lives, they have also been associated with serious injuries and fatalities. In the UK alone, several high profile deaths-including that of Ian Tomlinson and Jordan Begley-have occurred following police use of less lethal weapons. There are key questions around how so called less lethal force can impact the right to life, and their association with fatalities worldwide. Building on my PhD work focusing on injuries associated with Taser, this project will see the PI work with the UN Special Rapporteur to research the impact less lethal force has on the right to life in the UK and globally. Third, if it is important to attend to the situations in which force is used, it is also important to look at how such force is monitored and governed. This requires working with police and government to help understand what data on less lethal force should be gathered and analyzed, and working with the independent oversight bodies that monitor places of detention (including police custody) to ensure that they have the necessary research to enable them to document the LLF used by state authorities. The UN Subcommittee for the Prevention of Torture has highlighted the need for research to assist them in addressing and monitoring less lethal weapons and other physical infrastructure found in places of detention. The PI will work with key decision makers on these issues; with the UK government on reporting, and with oversight bodies via the SPT and its network of over 40 national bodies.

The overarching goal of this proposal is the development of an integrated technological platform for efficiently and safely engineering biology at the genome scale. I propose tackling this ambitious goal with three complementary work packages. Work packages are substantial and significant, but complementary to each other. The successful delivery of this vision will require the coordinated co-developments of all three work packages. First, I will develop a next-generation computer- assisted designer, capable of incorporating high- level, semantics-based features within higher eukaryotic genome design. The CAD software will provide sequence screening functionality to identify potentially harmful sequences. This sequence screening development will be coordinated with an international consortium backed by the Nuclear Threat Initiative (NTI), United Nations (UN) and World Economic Forum (WEF). To improve the efficacy of genome synthesis and assembly, I will apply state-of-the-art robotics for the automation of genome synthesis and use process engineering principles to monitor and schedule genome assembly pipelines. I will also develop a new concurrent genome assembly method to parallelise construction. Transplanting synthetic genomes from yeast to other organisms is a significant challenge. I will tackle this obstacle by developing a new standardised modular assembly kit to efficiently assemble large synthetic chromosomes. I will then exploring and optimising three distinct genome transfer methods to shuttle these synthetic chromosomes across kingdoms. To trace potentially dangerous synthetic genomes, we will develop genomic steganography to embed traceable watermarks, which are tamper-resistant and do not interfere with normal cellular physiology, across synthesised genomes. Finally, to minimise the risk of bioterrorism and bio-error arising from synthetic genome technology, I will develop SafeGuard technologies incorparating genetic code alterations and transcriptional, recom- binational, and protein stability switches to contain synthetic strains. I will characterise their respective performances under permissible and restrictive conditions. In summary, I propose a highly innovative and integrated engineering platform for genome design, manufacture, transfer and safeguarding.

In our changing world there is an increasing urgency to understand interactions among multiple environmental stressors, such as pollution and warming. Much of the concern surrounding multiple stressors is due to their potential to interact, creating more severe impacts than they would do independently. Freshwater ecosystems are particularly vulnerable and freshwater biodiversity is the most threatened across the globe: a recent report estimated average population declines of >80% among freshwater vertebrate species compared to <40% in terrestrial and marine species (since 1970; WWF Living Planet Report, 2018). Although the combined impacts of multiple stressors has started to receive more attention, our knowledge on their interactive effects still remains almost non-existent. In reality, stressors are unlikely to occur in the same space at exactly the same time, yet studies that measure the combined effects of multiple stressors often assume this to be the case. In other words, they lack temporal realism. Most of these studies also lack biological realism by quantifying the effects of stressors on model species at lower levels of organisation (e.g. range shifts, survival, abundance) and ignoring feeding interactions. Here, we will consider how the order, or sequence, of stressor events alters individual-to-ecosystem responses of freshwaters, with a focus on food web interactions. Ecosystems will have multiple responses to the multiple stressors they face, including changes in diversity, abundance, body size and feeding behaviour. Even minor alterations to any of these can shift food web structure, with implications for the effects of future stressors, yet these critically important interactions have been largely ignored to date. This leaves us with little or no predictive ability about the consequences of future change in natural systems. Therefore, here we will use mesocosm experiments to quantify the combined effects of staggered nutrient pollution and warming events (i.e. previous exposure) on freshwater ecosystems, and scale our results up to the catchment level by adapting a suite of dynamic water quality models. Our experimental results will be used to parameterize temperature and nutrient controlled population sizes and growth rates, and to simulate how these changed rates will alter food web structure at the larger river system scale. This interdisciplinary study will generate an unprecedented breadth and depth of data: from individual changes in fitness and population shifts in size structure to food web complexity. We will show how the order of multiple stressor events (i.e. previous exposure) affects community resistance and resilience to change. These unique data sets will allow us to ask numerous novel questions in pure and applied ecology, and to characterise the little known multiple impacts of multiple stressors on freshwater food webs. Such a comprehensive coverage of responses has never been attempted before and this study will address this glaring gap in our knowledge of stressor impacts.

Humans have massively altered flows of nitrogen on our planet, leading to both benefits for food production and multiple threats to the environment. There are few places on Earth more affected than South Asia, with levels of nitrogen pollution rapidly increasing. The result is a web of interlinked problems, as nitrogen losses from agriculture and from fossil fuel combustion cause air and water pollution. This damages human health, threatens biodiversity of forests and rivers, and leads to coastal and marine pollution that exacerbates the effects of climate change, such as by predisposing reefs to coral bleaching. Altogether, it is clear that nitrogen pollution is something we should be taking very seriously. The amazing thing is that so few people have heard of the problem. Everyone knows about climate change and carbon footprints, but how many people are aware that nitrogen pollution is just as significant? One reason for this is that scientists and policy makers have traditionally specialised. Different experts have focused on different parts of the nitrogen story, and few have the expertise to see how all the issues fit together. This challenge is taken up by a major new research hub established under the UK Global Challenge Research Fund. The "GCRF South Asian Nitrogen Hub" is a partnership that brings together 32 leading research organisations with project engagement partners from the UK and South Asia. All eight countries of the South Asia Co-operative Environment Programme (SACEP) are included. The hub includes research on how to improve nitrogen management in agriculture, saving money on fertilizers and making better use of manure, urine and natural nitrogen fixation processes. It highlights options for more profitable and cleaner farming for India, Pakistan, Bangladesh, Nepal, Afghanistan, Sri Lanka, Bhutan and the Maldives. At the same time, the hub considers how nitrogen pollution could be turned back to fertilizer, for example by capturing nitrogen oxide gas from factories and converting it into nitrate. The fact that all the SACEP countries are included is really important. It means that lessons can be shared on good experiences as well as on whether there are cultural, economic and environmental differences that prevent better management practices from being adopted. It is also important from the perspective of international diplomacy, and provides an example to demonstrate how working together on a common problem is in everyone's interest. It puts the focus on future cooperation for a healthier planet, rather than on the past. The South Asian case provides for some exciting scientific, social, cultural and economic research challenges. The first is simply to get all the researchers talking together and understanding each other. There are dozens of languages in South Asia, matching the challenge met when different research disciplines come together. This is where developing a shared language around nitrogen can really help. There are lots of nitrogen forms ranging from unreactive atmospheric nitrogen (N2), to the air pollutants ammonia (NH3) and nitrogen dioxide (NO2), to nitrate (NO3-) which contaminates watercourses, and nitrous oxide (N2O) which is a greenhouse gas. The impacts of each of these are being studied to provide a better understanding of how they all fit together. The result is an approach that aims to give a much more coherent picture of the nitrogen cycle in South Asia: What is stopping us from taking action, and what can be done about it. One of the big expectations is that the economic value of nitrogen will help. India alone spends around £6 billion per year subsidising fertilizer supply. It means that South Asian governments are strongly motivated to use nitrogen better. At which point research from the South Asian hub can provide guidance on where they might start.

Humans have massively altered flows of nitrogen on our planet, leading to both benefits for food production and multiple threats to the environment. There are few places on Earth more affected than South Asia, with levels of nitrogen pollution rapidly increasing. The result is a web of interlinked problems, as nitrogen losses from agriculture and from fossil fuel combustion cause air and water pollution. This damages human health, threatens biodiversity of forests and rivers, and leads to coastal and marine pollution that exacerbates the effects of climate change, such as by predisposing reefs to coral bleaching. Altogether, it is clear that nitrogen pollution is something we should be taking very seriously. The amazing thing is that so few people have heard of the problem. Everyone knows about climate change and carbon footprints, but how many people are aware that nitrogen pollution is just as significant? One reason for this is that scientists and policy makers have traditionally specialised. Different experts have focused on different parts of the nitrogen story, and few have the expertise to see how all the issues fit together. This challenge is taken up by a major new research hub established under the UK Global Challenge Research Fund. The "GCRF South Asian Nitrogen Hub" is a partnership that brings together 32 leading research organisations with project engagement partners from the UK and South Asia. All eight countries of the South Asia Co-operative Environment Programme (SACEP) are included. The hub includes research on how to improve nitrogen management in agriculture, saving money on fertilizers and making better use of manure, urine and natural nitrogen fixation processes. It highlights options for more profitable and cleaner farming for India, Pakistan, Bangladesh, Nepal, Afghanistan, Sri Lanka, Bhutan and the Maldives. At the same time, the hub considers how nitrogen pollution could be turned back to fertilizer, for example by capturing nitrogen oxide gas from factories and converting it into nitrate. The fact that all the SACEP countries are included is really important. It means that lessons can be shared on good experiences as well as on whether there are cultural, economic and environmental differences that prevent better management practices from being adopted. It is also important from the perspective of international diplomacy, and provides an example to demonstrate how working together on a common problem is in everyone's interest. It puts the focus on future cooperation for a healthier planet, rather than on the past. The South Asian case provides for some exciting scientific, social, cultural and economic research challenges. The first is simply to get all the researchers talking together and understanding each other. There are dozens of languages in South Asia, matching the challenge met when different research disciplines come together. This is where developing a shared language around nitrogen can really help. There are lots of nitrogen forms ranging from unreactive atmospheric nitrogen (N2), to the air pollutants ammonia (NH3) and nitrogen dioxide (NO2), to nitrate (NO3-) which contaminates watercourses, and nitrous oxide (N2O) which is a greenhouse gas. The impacts of each of these are being studied to provide a better understanding of how they all fit together. The result is an approach that aims to give a much more coherent picture of the nitrogen cycle in South Asia: What is stopping us from taking action, and what can be done about it. One of the big expectations is that the economic value of nitrogen will help. India alone spends around £6 billion per year subsidising fertilizer supply. It means that South Asian governments are strongly motivated to use nitrogen better. At which point research from the South Asian hub can provide guidance on where they might start.