Finding suitable and easily measurable early biomarkers for neurodegeneration and cognitive dysfunction represents the next frontier for prevention and early intervention strategies in diseases like Alzheimer’s Disease (AD). Our collective work in preclinical models has demonstrated that early-life adversity, such as stress or poor nutrition, can increase AD vulnerability, aggravate neuropathology and accelerate cognitive dysfunction. Neuroinflammation (driven by the brain’s primary immune cells, microglia) has been increasingly acknowledged as an important player in AD pathology and early-life adversity primes microglia, rendering them more sensitive to subsequent challenges. In addition, polyunsaturated fatty acids (PUFAs) and their derivatives play a key role in modulating microglia. N-3 PUFA (omega-3) metabolism is altered by early-life adversity and, recently, specialized pro-resolving mediators (SPMs; derivatives of omega-3) have been found to be altered in post-mortem AD brains. Finally, inflammation and metabolism are tightly connected in the context of early-life adversity and AD, presenting an opportunity to use metabolic sensors as potential biomarkers of (neuro)inflammation. We thus propose a translational project that will leverage data and bio-samples from four established human cohorts as well as more than 10 established in vivo and in vitro mouse and rat preclinical models. We will use these to identify early biomarkers of neurodegeneration and establish the causal role of and detailed mechanisms for early-life adversity and omega-3 in microglial priming in increasing the risk of neurodegeneration and AD. SOLID will complete a discovery program in humans aimed at identifying early biomarkers of neurodegeneration and cognitive decline. The second, parallel, work program will be to back-translate candidate and newly identified biomarkers to validated animal models of cognitive decline and AD and test the temporal and causal relationship of these biomarkers to the central neuroinflammatory changes. We will use several innovative approaches including microglial functional assays, microglia depletion strategies, omega-3 and SPM assessment, organotypic slice cultures, and transgenic rodent models; testing the causal role of early-life adversity, omega-3 and microglia. The third work program will test the potential for early supplementation with omega-3 to protect against early-life adversity-induced aggravation of neurodegeneration in AD mice and against cognitive deficits in a healthy aging human population. On completion of this proposal, we will have identified i) unique profiles of early biomarkers (cytokines, PUFAs, SPMs and metabolic sensors) predictive of cognitive dysfunction and neurodegeneration; ii) the causal role of early-life adversity in predisposition to AD; and iii) an omega-3 and SPM strategy for alleviating these effects.

Modern slavery is a pervasive and persistent problem with estimates that globally 24.9m people are in forced labour. Eradicating modern slavery is a grand challenge made arduous by ongoing COVID-19 effects that are increasing commercial priorities in business decision making, relative to social factors. Internationally, transparency in supply chain (TISC) principles lie at the heart of recent legislation such as the UK Modern Slavery Act (2015) and Australia's Modern Slavery Act (2018). The premise is that transparency in large companies' supply chains will commit them to more rigorous investigations and management of modern slavery in global supply chains. However, links between transparency and socially responsible practices are poorly understood; research in multi-tier supply chains is limited and disclosure is often symbolic rather than substantive, with modern slavery statements providing vague commitments that lack details of action undertaken. Hence, the aim of this research programme is to build capacity for developing an understanding of how business decision-makers' behaviours and attitudes impact socially responsible supply chain practices. Ultimately, this will support policy implementation in a manner that prevents the creation of modern slavery victims and the high human costs of survivor recovery and support. The programme will extend relationships that have already been established with key stakeholders in: policy making (UK Home Office), policy implementation (Crown Commercial Service, CCS), large corporations, NGOs (e.g. the Ethical Trading Initiative, ETI), professional associations (Chartered Institute of Procurement and Supply, CIPS) and academia. The research methodology recognises the visually connoted themes in modern slavery, such as transparency. Therefore, photo-elicitation methods will be utilised in conjunction within a participatory action research (PAR) approach. Photo-elicitation will be utilised to bring to the surface the way people see modern slavery both in private and at work. It will establish practitioners' attitudes and actions relating to modern slavery and will reveal participants' perceptions about their ability to influence prevailing issues (agency). The combination with PAR will enable theoretical insights to be assessed in practical contexts. This will be through Government procurement policy and practice and government contractors' supply chain decision makers. The participatory approach will raise the consciousness of all involved in the research programme, helping to identify opportunities and consequences of change to accommodate more socially-oriented supply chain practices. The fellowship will be pivotal in building capacity to extend these relationships and, through research, influencing the development of coordinated changes to policy and practice. The CCS will provide access to participants in selected tier-one suppliers, through which supply chain practices will be investigated. Importantly, the programme will engage and co-create research methods with ETI who work directly with individuals and organisations to combat modern slavery through training and education. My fellowship will engage with RMIT University, Australia (Business and Human Rights Centre), CIPS and the International Slavery Museum as project partners for research co-design, recommendations and dissemination of results. The core outcome of the programme is to contribute to the development of high-quality research on transparency in supply chains that can be used to underpin socially responsible legislation and organisational practice.

International research suggests that in response to climate change global cities are now engaging in strategic efforts to effect a low carbon transition. That is, to enhance resilience and secure resources in the face of the impacts of climate change, resource constraints and in relation to new government and market pressures for carbon control. But significant questions remain unexplored. First, limited research has been undertaken internationally to comparatively examine how different cities in the north and south are responding to the challenges of climate change. Second, it is not clear whether the strategic intent of low carbon transitions can be realised in different urban contexts. Consequently, we propose to establish an international network, to be undertaken between leading scholars on urban climate change responses as an important step towards addressing these deficits. The network will focus on the research and policy issues involved in comparing and researching the broader dynamics and implications of low carbon urbanism. This network includes Australia, China, India, South Africa and the US and builds on existing scholars and research teams with whom we currently have bilateral and ad hoc collaborations. Our proposed collaboration is designed to create greater density of network connections and enhancing the depth of each connection by three sets of initiatives: 1. International Networking Opportunities: The first element of the ESRC initiative will be to support significant international research opportunities for UK researchers. We will undertake programmed and structure visits to each national context to: increase knowledge of one another's research and plans; to gain intelligence about the research landscape in the partner countries in this field in order to build up a global picture of research expertise; to exchange ideas about possible future collaborative research projects; and to build personal relationships that are at the heart of successful long-distance research partnerships. 2. International Comparative Collaboration: The second element of the network is to facilitate interaction between the partners in the research network and with a wider group of UK and international researchers through two connected forum that will meet four times. A. International Research Workshops (Network partners plus other relevant UK and international researchers). These meetings will focus primarily on enhancing comparison and collaboration with a wider group of researchers but will also serve as an important opportunity for developing publications in the form of special issues and edited collections. B. Network Partners Research Forum (Network partners only). The network will also sponsor a number of much smaller research forums, focused on the network partners. These workshops will enable a structured and protected space for the partners to share the findings from their ongoing work, and to explore and examine the implications of the issues and themes emerging from the larger workshops in this context. 3. International Network Infrastructure: The third element will focus on establishing the necessary infrastructure for promoting effective international research collaboration. The network will pursue two projects. A. Information Infrastructure: Durham will establish a website that facilitates collaboration among international partners. All partner researchers and institutions will have the opportunity to present and regularly update information about their ongoing research. The website will also serve as a base for communicating about events, visits, awards, etc. The website will also host audio and video recordings of workshops. B. International Network Coordinator: Additionally Durham will support a 20% network coordinator to manage and organize the visits, workshops, teleconferences and the website.

International research suggests that in response to climate change global cities are now engaging in strategic efforts to effect a low carbon transition. That is, to enhance resilience and secure resources in the face of the impacts of climate change, resource constraints and in relation to new government and market pressures for carbon control. But significant questions remain unexplored. First, limited research has been undertaken internationally to comparatively examine how different cities in the north and south are responding to the challenges of climate change. Second, it is not clear whether the strategic intent of low carbon transitions can be realised in different urban contexts. Consequently, we propose to establish an international network, to be undertaken between leading scholars on urban climate change responses as an important step towards addressing these deficits. The network will focus on the research and policy issues involved in comparing and researching the broader dynamics and implications of low carbon urbanism. This network includes Australia, China, India, South Africa and the US and builds on existing scholars and research teams with whom we currently have bilateral and ad hoc collaborations. Our proposed collaboration is designed to create greater density of network connections and enhancing the depth of each connection by three sets of initiatives: 1. International Networking Opportunities: The first element of the ESRC initiative will be to support significant international research opportunities for UK researchers. We will undertake programmed and structure visits to each national context to: increase knowledge of one another's research and plans; to gain intelligence about the research landscape in the partner countries in this field in order to build up a global picture of research expertise; to exchange ideas about possible future collaborative research projects; and to build personal relationships that are at the heart of successful long-distance research partnerships. 2. International Comparative Collaboration: The second element of the network is to facilitate interaction between the partners in the research network and with a wider group of UK and international researchers through two connected forum that will meet four times. A. International Research Workshops (Network partners plus other relevant UK and international researchers). These meetings will focus primarily on enhancing comparison and collaboration with a wider group of researchers but will also serve as an important opportunity for developing publications in the form of special issues and edited collections. B. Network Partners Research Forum (Network partners only). The network will also sponsor a number of much smaller research forums, focused on the network partners. These workshops will enable a structured and protected space for the partners to share the findings from their ongoing work, and to explore and examine the implications of the issues and themes emerging from the larger workshops in this context. 3. International Network Infrastructure: The third element will focus on establishing the necessary infrastructure for promoting effective international research collaboration. The network will pursue two projects. A. Information Infrastructure: Durham will establish a website that facilitates collaboration among international partners. All partner researchers and institutions will have the opportunity to present and regularly update information about their ongoing research. The website will also serve as a base for communicating about events, visits, awards, etc. The website will also host audio and video recordings of workshops. B. International Network Coordinator: Additionally Durham will support a 20% network coordinator to manage and organize the visits, workshops, teleconferences and the website.

Both "Advanced and Functional Materials" and "Biotechnology" have been identified as pervasive technologies for future manufacturing activities in the UK. This Fellowship will join these two areas by developing chemical and biological technologies to create advanced functionalized biomaterials, taking advantage of the Fellow's cross-disciplinary expertise at the chemistry/biology interface. Working with manufacturers of biomaterials for healthcare and personal care, hybrid biomaterials will be produced that are able to heal and diagnose. An aging population needs cheaper biomedical materials with improved performance, but robust chemical and biotechnological processes for biomaterial functionalization are needed to create these materials. High-throughput modular methodologies are proposed for the modification of nanostructured biomaterials that will allow manufacturers to create tailored high-quality products for different markets, methodology that is able to respond quickly to the needs of customers (e.g. patients). These methodologies will draw on the UK's strengths in biotechnology to achieve a step change in cost reduction and an increase in performance; even a small reduction in costs to the NHS would bring significant benefits to the UK. The Fellowship will address this problem through work in three key theme areas: (1) developing simple, cheap and easy-to-access methodologies for adding reactive nanoparticles to biomaterials; (2) using synthetic biology and biotechnology to functionalise biomaterials; (3) using synthetic chemistry to produce value-added biomaterials. Each theme area has been identified as an exciting and highly interdisciplinary field that is ripe for exploitation, but where poor communication between experts in different fields is hampering progress. For example, there is insufficient involvement of industrial biotechnologists, synthetic chemists and supramolecular chemists in biomaterials manufacture despite clear synergies in expertise and the importance of this area to UK manufacturing. This Fellowship will build networks between biomaterials academics and biomaterials manufacturers, with partnerships backed up through meetings, researcher exchanges and follow-on funding. The Fellow will stimulate new innovative approaches to collaborative research by interacting with leading international researchers in Europe, the US and Australia/New Zealand who have complementary expertise to that of the applicant. The applicant will engage with leading UK manufacturers and international academic researchers, both through personal meetings and by helping to organise industry-academia meetings and developing new funded collaborations. At the end of this Fellowship, new easy-to-use chemical and biochemical methodologies will have been developed that will have applicability across academic and non-academic biomaterials research, producing new opportunities for UK manufacturing.