Assessment of the potential impact of future climate change on human health and well-being (the latter via effects on animal health) is hindered by the sheer number of pathogens, their diversity, varied linkages to climate and ecosystems and, often, lack of data. Here we propose to exploit a unique database developed at the University of Liverpool which will soon contain a set of records for all known pathogens of humans and domestic animals. We will use expertise present within the University of Liverpool, the international co-investigators and our project partners to generate a subset of the list, namely all those pathogens that occur in proximity to the UK, France and the Netherlands or threaten these countries; are of major impact in terms of the magnitude and likelihood of impact on human health or well-being; and have epidemiological linkages to temperature or moisture levels in air or the environment and, hence, may be expected to be susceptible to the effects of climate change. This subset of diseases will be subjected to qualitative or quantitative risk assessment to estimate how they will change (in terms of distribution, incidence and severity) under scenarios of future climate change within the next half-century. Our underlying principle is that the data and pathways on which our conclusions are based should be fully recorded, referenced and transparent; as better data become available, it will be possible to update the model outputs. A benefit of our approach is that it is 'bottom-up', at the start giving equal weight to all possible pathogens that could be affected by climate change, and then reducing the list according to agreed criteria. This approach is balanced, allowing the conclusion, for example, that the highest-impact pathogens are largely insensitive to climate change. By contrast, most previous assessments of the impacts of climate change are top-down, starting (and often ending) with the premise that a few key vector-borne pathogens of (usually) humans (malaria, dengue, yellow fever) need urgent consideration. We will listen closely to stakeholders and end-users while designing our risk assessment pathways, and wish to communicate our scientific approaches and findings to them effectively. To the end, we plan to adopt participatory methods throughout the project.

Most recent scientific efforts have focused on examining toxicities of manufactured nano-particles (MNPs) only in source materials. By not evaluating MNPs at the point of exposure, these efforts fail to address the relevant question of whether or not consumer-product-derived MNPs are of concern to public health and the environment. The proposed US-UK consortium, 'Risk Assessment for Manufactured Nanoparticles Used in Consumer Products (RAMNUC)', provides a systematic, multidisciplinary approach, including both experimental and computational tools and projects, for predicting potential human and environmental risks associated with the use of selected consumer products that respectively incorporatezinc oxide, silver, and cerium dioxide nanoparticles. The overall hypothesis of the RAMNUC project is that MNPs at the point of exposure for both humans and aquatic animals will substantially differ in both physicochemical and toxicological properties from MNPs at the source (synthesized in the laboratory or acquired commercially). These differences may have significant consequences with respect to MNPs' bioavailability, alterations of immunity, induction of oxidative stress, inflammation, disease processes, and other toxicity measures. We will assess intracellular and extracellular bioavailability and toxicity of the selected MNPs, as synthesized and as incorporated in consumer products, using both in vitro and in vivo experiments. Tested MNPs will be controlled or well characterized for their physical (e.g., size, shape, state of agglomeration/aggregation) and chemical properties (e.g., composition, functionalization, surface chemistry). Hence, our proposed in vitro and in vivo studies will produce mechanism-based results relating toxic effects to MNP physicochemical properties. The RAMNUC Consortium will also include a novel human exposure simulation study that will produce realistic estimates of MNP exposures to consumers. Data generated from these mechanistic experiments will be integrated into the mechanism-based computational modules of two existing source-to-exposure-dose-to-effects modeling systems, allowing for rational extrapolation and generalization in MNP risk assessment. Built upon the inter-institutional expert structure, the RAMNUC consortium serves as a model for systematically addressing complex problems associated with MNP risk assessment and will generate results that will contribute to our very limited knowledge about health risks associated with the use of nano-technology based consumer products.

The broad theme of the research training addresses the most rapidly developing parts of the bio-centred pharmaceutical and healthcare biotech industry. It meets specific training needs defined by the industry-led bioProcessUK and the Association of British Pharmaceutical Industry. The Centre proposal aligns with the EPSRC Delivery Plan 2008/9 to 2010/11, which notes pharmaceuticals as one of the UK's most dynamic industries. The EPSRC Next-Generation Healthcare theme is to link appropriate engineering and physical science research to the work of healthcare partners for improved translation of research output into clinical products and services. We address this directly. The bio-centred pharmaceutical sector is composed of three parts which the Centre will address:- More selective small molecule drugs produced using biocatalysis integrated with chemistry;- Biopharmaceutical therapeutic proteins and vaccines;- Human cell-based therapies.In each case new bioprocessing challenges are now being posed by the use of extensive molecular engineering to enhance the clinical outcome and the training proposed addresses the new challenges. Though one of the UK's most research intensive industries, pharmaceuticals is under intense strain due to:- Increasing global competition from lower cost countries;- The greater difficulty of bringing through increasingly complex medicines, for many of which the process of production is more difficult; - Pressure by governments to reduce the price paid by easing entry of generic copies and reducing drug reimbursement levels. These developments demand constant innovation and the Industrial Doctorate Training Centre will address the intellectual development and rigorous training of those who will lead on bioprocessing aspects. The activity will be conducted alongside the EPSRC Innovative Manufacturing Research Centre for Bioprocessing which an international review concluded leads the world in its approach to an increasingly important area .

This project will develop a user-friendly tool that will enable decision makers to explore the costs, benefits and uncertainties of introducing point-of-care (POC) testing for chlamydia infection in different clinical settings and target populations. This tool will allow comparison of the costs and benefits of the status-quo of current laboratory assays and existing clinical pathways with a clinical pathway built around novel POC diagnostics, using a dynamic transmission model of chlamydia infection. The Health Protection Agency is leading the project and conducting the modelling and health economic work. A strong group of inter-disciplinary expert collaborators (including academic, industry and US partners) are involved in the project.