The amide bond is arguably the most significant in pharmaceutical chemistry, featuring in a host of important everyday pharmaceuticals for the treatment of ulcers, high cholesterol and pathogenic infections by bacteria and viruses. It is vital therefore that there exist atom efficient and sustainable green chemical methods for the synthesis of pharmaceutical amides. However, industrial synthetic methods for the preparation of amides suffer from the use of complex or hazardous reagents to accomplish their chemistry and generate a large amount of waste. Because of this lack of efficiency, industrial synthetic chemists are increasingly turning towards 'biocatalysis' or 'Industrial Biotechnology' as the preferred method of synthesising molecules for pharmaceutical production. Biocatalysts, such as enzyme or microbes, typically achieve the synthesis of chemical bonds with excellent atom efficiency and selectivity, and Nature is also expert at synthesising amide bonds, which are the major bonds that hold the structure of proteins together. Until now however, biocatalysts for the formation of amide bonds have received little attention for industrial application, even though such enzyme reactions feature at the top of the list for many chemists looking for biocatalytic solutions to synthetic problems. This is because biocatalytic methods for amide bond formation in Nature, while efficient, are often complex, and difficult to apply out of their natural context. A recently discovered group of enzymes, which we have called amide bond synthetases (ABSs), offers new and unexplored promise for biocatalytic amide bond formation, as their reaction chemistry is comparatively simple, and also because the kind of amide bonds that they form, are much more closely related to molecules of real pharmaceutical interest than has previously been the case. In this project, which is a collaboration between biochemists and synthetic chemists at York, and in association with GSK and also the University of Freiburg, we propose to thoroughly investigate the synthetic potential of the new ABS enzymes. First we will define the potential and limitations of the natural enzymes using a mixture of synthetic chemistry and biocatalysis. We will then use the recently-determined structure of the ABS enzyme McbA to engineer the enzyme, expanding its potential for the catalysis of the synthesis of a much wider range of pharmaceutically relevant molecules. We will also use contemporary protein evolution techniques to adapt the enzymes to act on alternative substrates that are of interest to industrial collaborators. We will also apply new techniques in enzyme cofactor recycling to allow us to scale up the amide bond forming reactions, and also immobilise the enzymes in order to establish a flow biocatalysis system for amide synthesis. Finally, we will combine ABSs with other enzymes to create 'cascades' for the synthesis of amides from readily available alcohol and amine substrates. Together, the project will establish a new frontier in biocatalytic amide bond formation with a view to more sustainable chemical processes for the industrial synthesis of pharmaceuticals.

We request funding for field research on ancient urban planning on the East African Swahili coast. This funding will support three seven-week field seasons of archaeological research at Songo Mnara, a Swahili stonetown on the southern coast of Tanzania, along with subsequent analysis of data recovered and dissemination of research results. Stonetowns, the quintessential expression of Swahili culture, are known along the eastern coast of Africa, and represent an important form of autochthonous urbanism that linked Africa with the Indian Ocean world system. A World Heritage Site, Songo 1vlnara is recognized as the most impressive of all Swahili townscapes and considered to be the quintessential expression of the coral-built tradition for which the coastal towns became famous. The town has a full range of domestic and non-domestic structures, with more than 40 coral-built houses and room-blocks, 5 mosques and multiple cemeteries. Occupation of the site was brieC li'otn the 14'" to 16'" centuries AD, coinciding with the golden age of Swahili stonctowns along the coast. Research at Songa .Mnara adopts a spatially-integrated approach to Swahili economic and ritual/religious practice that will allow us to isolate both deliberately-planned elements of the town (central cemeteries and open spaces) and elements that might have been created through exigency, particularly in the realm of domestic architecture. The proposed fieldwork will explore the urban space of Songo Mnara at four interlinked scales: (l) Household activities will be sought through systematic excavations within and around buildings at the site; (2) Public and communal practices will be recovered through geo archaeology, geophysical survey, and excavations across the open areas and monuments of the site; (3) The site plan will be accurately plotted; and (4) The site will be positioned within its broader landscape through off-site survey and geophysics. Analysis of recovered materials will take place first in the field, and then in the USA and UK over the periods between field seasons and in the year all the final field season. The project will be conducted in collaboration with local authorities and UNESCO partners, and accompanied by conservation efforts on the important coral architecture at the site; funding for this aspect is being sought separately. Intellectual Merit Research at Songo will contribute to discussions of urban planning in Swahili and other urban contexts. The exceptional preservation at Songo Mnara will allow for the construction of a robust dataset to explore the way that Swahili towns were both planned and unplanned, with their components altering an insight into the priorities and social negotiations of their inhabitants. This work will contribute substantially to discussions of organizational principles and levels of meaning in ancient town plans more generally, and especially to research on aspects of town layouts that were recursively linked to movement and activity. In this way, Swahili town plans offer a dramatic case study in which to break down the 'false dichotomy' between planned and organic, and explore the importance of spatial practice in the negotiation of global and local economic and religious practice. Broader Impacts This project will offer important training for American, British, and Tanzanian students, both graduate and undergraduate. The training of students from the University of Dares Salaam is significant, as it provides these students with hands on experience with up-to-date equipment and techniques. The preservation and conservation of Songo Mnara-which remains an "endangered" World Heritage Site-is a priority for the Tanzanian Department of Antiquities, who have invested in the site as a tourist destination. Archaeological research at the site also aligns with the interests of the local residents, who have an active village 'Ruins Committee' with which we will closely work. A long term commitment to archaeological research at the site will provide important educational opportunities to demonstrate the unique role that archaeology can play in its preservation and documentation.

Air pollution affects the health of the world's population. The WHO estimate that 3.7 million deaths are annually attributable to outdoor air pollution (6.7% of all deaths globally) and urged Member States to develop air quality monitoring systems and health registries to improve surveillance for all illnesses related to air pollution. Establishing and maintaining air quality monitoring infrastructure can be costly. Furthermore, air quality monitoring alone does not provide the basis for robust analysis of health outcomes or onward air quality management. Health risks due to air pollution in densely-populated Indonesian urban areas are increasingly associated with transport activities, whilst forest fire emissions further exacerbate health impacts associated with air-pollution. This represents a major health concern for Indonesia with both economic and welfare implications. In order to enable effective control measures that are feasible within wider development, welfare and economic goals, much improved quantification of the exposure of the population to pollution is required. To enable such quantification, the contributions from long-range and local sources pollutants and the availability of suitable health data to the determine health impacts of pollutant exposure must be established. The UDARA project will be a multidisciplinary collaboration between the University of Manchester and 3 Indonesian Institutions; the Institut Teknologi Bandung, National Nuclear Energy Agency of Indonesia and the University of Padjadjaran involving exposure scientists, atmospheric scientists and health scientists. The project will develop a new approach for providing reliable exposure estimates for analysing the impact of air pollution on health outcomes in Indonesian cities. It will employ a new methodology developed within the EU ESCAPE project in response to the lack of European-specific data on exposure-response relationships and the uncertainty introduced into health outcome analyses by the use of varied exposure models. ESCAPE developed standardised protocols for developing and testing LUR models, while still allowing sufficient flexibility to incorporate application specific factors. The further refinement to incorporate remote sensing and chemical transport model outputs has improved model performance in complex pollution climates such as experienced in Indonesia. The ESCAPE project involved the development of both classic and hybrid models but their performance in the sort of pollution climate seen in Indonesian urban areas has yet to be investigated. Within UDARA, we will collect new data in Jakarta, a heavily populated city with a pollution problem dominated by urban emissions, and a second city in Sumatera substantially influenced by seasonal biomass burning. The highly spatially resolved measurements of both gaseous and particulate pollutants and data from two 3D pollution models will be used within the ESCAPE methodology to derive pollutant exposure estimates for the two cities. We will additionally conduct an evaluation of the quality and quantity of Indonesian health outcome data that can be used for subsequent future epidemiological studies. UDARA will thereby provide a new methodology and robust basis for evaluating the health outcomes from air pollution exposure in Indonesia.

As the global population continues to increase from 7.5bn (2019) to 9.5bn (2050) coupled with increased urbanisation and industrialisation we will need to better (re)utilise resources to sustain our chemical, material and energy needs. In 2015, the United Nations recognised these concerns and established 17 Sustainable Development Goals (SDGs) to protect the future of our planet and its inhabitants. In particular, SDG 12, "Sustainable Consumption and Production", focuses on better resource utilisation, resource recovery, doing 'more with less' and moving from linear to circular economies, which is recognised as strategically important by the UK government and industries. For example, the UK Chemistry Council's Chemicals sector Strategy (http://tiny.cc/mru3fz) highlights a greater emphasis on sourcing of renewable raw materials, ensuring products are free from pollutants and innovating to reduce their carbon footprint. The UK Industrial Strategy and DEFRA 25 Year Environment Plan both highlight circular, green economies and developing leadership. Recent Science Innovation Audits (Northern Powerhouse: Chemical and Process Sector Science http://tiny.cc/tsu3fz, and the Bioeconomy in the North of England http://tiny.cc/jwu3fz) highlight the importance of our chemicals and bioeconomy sectors, interconnectivity of chemistry and biology, the importance of training, re- and up-skilling, and continual professional development in physical and biological sciences. The chemicals sector is one of the largest UK manufacturing sectors with a turnover of £48.7bn and employs ca. 140,000 people and increasingly becoming more interdisciplinary. To be globally competitive, UK businesses will need to transform current manufacturing practices, which are often linear and resource-depleting, to those that are circular, resource efficient, and sustainable via re- and up-skilling its current workforce so as to accelerate impact. In partnership with industry, this project will develop and embed: 1. A highly re- and up-skilled cohort of research scientists with excellence and leadership in circular, resource efficient, sustainable manufacturing impacting current and future knowledge-driven business decisions in chemical- and allied-industries, thus, improving global sustainability. 2. Person specific doctoral learning contracts (PSDLC) designed to suit the needs of the individual, employer and academic supervisor. Often, a lack of clear understanding of expectations has been both a downfall and barrier for successful industrial PhDs in the past. Projects will be industrially-driven via our project partners, thereby accelerating innovation and boosting economic growth. 3. Support mechanisms that encourage peer learning and reflection via regular cohort meetings to discuss issues specific to the industrial students and identify areas for improvement. Similarly, a two-way buddy scheme (academic student/industrial student) will be implemented, allowing both to benefit from the other's experience. 4. New (and extended current), flexible, credit-bearing in-house and virtual CPD modules to reflect specific needs. For example, training modules in change management, business strategy and responsible research innovation will be developed and delivered. 5. Mechanisms that reward prior experiential learning so as to fast track doctoral training will be investigated and incorporated in bespoke PhD programmes. 6. Proactive stakeholder working groups comprising project partners (industry and professional bodies), who will meet quarterly for the first two years to continue to de-risk barriers, innovate and disseminate the benefits of this programme both internally and externally to their organisation. 7. Structures and mechanisms will be put in place that encourage recruitment, retention and progression of under-represented minorities, such as, BAME, and respect equality, diversity and inclusion

Well-conducted systematic reviews contain a comprehensive summary of the available evidence on a given topic, and are valuable sources of information for decision-makers. However, most systematic reviews focus on establishing the benefits rather than the side effects of treatments. Whilst methods for identifying evidence relating to the benefits of treatments are well established, little is know about how best to find the evidence on the side effects of a treatment. By using a series of systematic reviews as case studies this research (by a health information scientist) will investigate: 1) Which types of research are most helpful for identifying information on side effects 2) Which are the best places to look for information on side effects (e.g. Internet, databases, etc.) 3) What are the best ways to search for side effects in the databases available By providing guidance on what types of research to look for, where to look and how, this study will help researchers produce more balanced systematic reviews that look at both the benefits and harms of treatments. This should lead to better informed decisions by health care providers and patients, and could in turn lead to fewer patients being harmed by potentially avoidable side effects.