Tissue engineering - aimed at developing "lab-grown" organs and tissue by combining appropriate scaffolds and cells - could solve one of the biggest medical problems of our times, the shortage of donor organs. While the pool of scaffold materials is large (e.g. natural/synthetic biomaterials), there is consensus that the extracellular matrix (ECM) of the target tissue is an excellent choice as it possesses native structural and biomechanical properties. ECMs can be derived from cadaver tissue (e.g. from animals) through a process called decellularization, by which the tissue undergoes several cycles of flushing with detergents and enzymes. A successfully decellularised tissue is characterised by the absence of cellular material and the presence of an intact ECM. Imaging, for assessing the ECM, is an extremely important tool for the development of decellularisation methods that are simultaneously gentle and effective. This project is about developing a new imaging tool for characterising decellularised tissue based on x-ray micro computed tomography (CT). Since micro-CT is a non-destructive technique, the inspected samples can be used further in longitudinal studies or be implanted into animals to test their performance in vivo. In comparison, the current gold standard techniques for inspecting ECMs (histology, electron microscopy) require that samples are sliced, sectioned and/or stained in preparation for being imaged, prohibiting using them in any further studies. A number of substantial developments will be needed before micro-CT can become a valuable tool for validating decellularisation techniques and other methodologies in tissue engineering. Currently, micro-CT fails to meet the complex imaging needs of this field, which often requires multi-scale and multi-contrast approaches. First, a micro-CT machine with zooming in capabilities would be required to inspect the multi-level structure of ECMs. Second, decellularised tissue generally exhibits weak x-ray attenuation; hence, the micro-CT machine should provide access to phase contrast alongside attenuation contrast, which is known to provide a much better visualisation of tissue scaffolds than the latter. The micro-CT machine proposed here will have both these functionalities. It will exploit an innovative imaging mechanism that is underpinned by the idea to structure the x-ray beam into an array of narrow (micrometric) beamlets via a mask placed immediately upstream of the sample. This provides flexibility in terms of spatial resolution, as this metric - unlike in conventional micro-CT scanners - is not defined by the blur of the source and detector. Instead, resolution is driven by the beamlet width, which can be made smaller than the intrinsic system blur, bearing unique potential for fast resolution switching and multi-scale imaging. Second, it provides access to complementary contrast channels (phase, ultra-small angle x-ray scattering). These channels result from small x-ray photon deviations which occur alongside attenuation when x-rays interact with matter. While most conventional micro-CT scanners are blind to these effects, the machine proposed here will enable their detection, allowing to reconstruct three sets of complementary tomographic images for each sample. While the phase channel can provide a much higher contrast-to-noise ratio than the attenuation channel, the ultra-small angle x-ray scattering channel encodes the presence of sub-resolution features in a sample. The latter bears unique potential for image-guided zooming in. The project will culminate in the design, construction and test of an experimental prototype for image-guided multi-scale and multi-contrast imaging with a field of view of up to 10 cm by 10 cm, which may be expanded to larger dimensions in the future. A broad range of decellularised tissues will be scanned, and the results benchmarked against the current gold standard (histology or electron microscopy).

The importance of international collaborations in research is recognised both by individual researchers and by institutions and government, with studies showing that the average impact of publications resulting from these collaborations is significantly higher than that of papers with national co-authorship. This collaborative project between leading academic groups in the UK and India addresses the purification operations used to manufacture biopharmaceuticals e.g. antibodies and hormones such as insulin. They are supported in this activity by four industrial partners selected to provide support to the analytical and manufacturing aspects (being leading companies in their respective areas) as well as to provide a route to transfer the findings of the research to practice. Many of the latest drugs are based upon proteins rather than traditional small molecules (e.g. antibiotics). These protein drugs are produced for the treatment of diseases such as cancer. Antibodies such as Herceptin dominate this market. The research collaboration described here is focused on the study of the performance of the core purification method used for the manufacture of biopharmaceuticals - chromatography. Specifically we seek understand the mechanisms which determine the manufacturing lifetime of this operation and can lead to changes in performance. This issue presents a major hurdle to manufacturers. They must establish a robust purification process with acceptable costs for production before seeking approval for such medicines from the regulatory agencies. Clearly problems leading to delays can lengthen the times before medicines can made available to patients. This can affect both manufacturers of new products and those seeking to compete at reduced costs and widen the availability of this class of medicines (products often termed biosimilars). In comparison to other areas of manufacturing, bioprocessing is unusual in several respects. Typical product quantities are small (~250 kg/year), but are manufactured to extremely high purity and quality specifications (impurities < 0.001%). The variability typically seen in these processes has led to extremely regulated manufacturing, whose dictum is that "the process is the product". No significant change can be made to a licensed manufacturing process without detailed and time-consuming review by the international regulatory authorities. Developing and validating a bioprocess for manufacture takes ~10 years at a cost of £800M. Development is often empirical, with little use of modelling compared to other manufacturing sectors. These unusual features emphasise the need for a more fundamental understanding of the bioprocess. This research programme is structured towards building mechanistic understanding of the events that lead to changes in chromatographic performance in the manufacturing setting. There is evidence for several mechanisms the first stage is to structure these into a series of proposed mechanisms. Following consultation and study of historical data from our industrial partners we will embark upon experimental studies. Here detailed analytical measurements are required to identify specific critical species that are associated with the root cause of the mechanism. The project is to be led by UCL in London and IIT in Delhi in collaboration with IIT Bombay and the University of Kent. These academic groups are supported by industrial partners; ABB, Dr Reddy's Labs, GE Healthcare, Genzyme, PerkinElmer and Regeneron.

By the middle of this century, two thirds of the world's population will be urban - equivalent to around 6.3 billion people. Mismanagement of these urban areas will adversely affect the health and well-being (i.e. how people experience their lives and flourish) of the population, and lead to social and environmental injustice. It has long been recognised that good quality cultural, social, built and natural environments within cities provide benefits in terms of health, well-being and equity of urban residents. Conversely, poor quality environments negatively affect the health and well-being of citizens and have negative economic consequences. With increasing urbanisation and changes in climate, the built, cultural, social and natural environments within cities will come under further pressure. While the relationships between selected environment quality parameters, such as noise and air pollution and health, have been well characterised, relatively little is known about the relationship between other quality measures, or endpoints, of economic and societal well-being and health. A major reason for this limited understanding is that while much data on city environments exist, this is fragmented across numerous data owners, is not joined up or at suitable granularity. As these existing datasets have been collected for other reasons, they are not always in a form where they are useful for a wide variety of purposes or for future needs. Data on some important parameters simply does not yet exist. Additionally, specialists in the different disciplines needed to tackle these complex issues often work in isolation. By bringing data together, breaking down barriers across research disciplines and exploiting and developing new monitoring, modelling and analytical technologies (e.g. wireless sensing networks, wearable devices, drones, crowdsourcing, 3D models of cities and virtual reality), it should be possible to provide a holistic analysis of the quality of the environment with a city that can be used by many different stakeholders (e.g. researchers, policy makers, planners, businesses and the public) to address their needs. This holistic analysis will then provide us with a better understanding of how to manage city environments and will provide long-term benefits to citizens and the economy. The York City Environment Observatory (YCEO) initiative will address this major knowledge gap by providing a framework, tools and conceptual models at the urban scale that can be rolled-out to assist with governance of environments in York and other cities in the UK and around the world. In this diagnostic phase project, experts from a diverse range of sectors and disciplines, will work together in a holistic way to design and lay the groundwork for establishing the YCEO. The consortium will work with a range of stakeholders and look to the past, present and future in trying to diagnose and predict environmental issues for York and their associated human health and well-being and economic impacts. We will build on York's strong track record in open data and combine data and models in order to do this. This diagnostic project will allow us to develop a prototype design for the YCEO, to be implemented within the next five years and a roadmap for achieving this. The YCEO will be designed to provide the evidence-base for making decisions on how best to manage and enhance the social, cultural, built and natural environment across city systems now and into the future, and in this way, improve the health, well-being and equity of citizens and the economy of the city. The YCEO will also aid local, national and international stakeholders (including planners, businesses, residents and community groups) to come up with low cost and innovative solutions to a range of problems identified as part of this diagnostic phase of the Urban Living Partnership.