CERBERUS - Summary It has been estimated that there is more microbial life under our feet in deep rocks and sediments than there is on the surface or our planet - yet there are still large gaps in our understanding of how this life survives in the absence of light and photosynthesis. There is now strong evidence that hydrogen gas, produced by water reacting with rocks, is an important source of energy (or food) for subsurface microbes - and that the use of this hydrogen dates back to the very first life that arose on Earth. A very substantial source of subsurface hydrogen is generated from the grinding of rocks along geological faults, with freshly fractured rock surfaces 'splitting' water to form hydrogen gas, alongside an equal amount of oxygen equivalent (oxidants) such as the highly oxidizing and toxic chemical hydrogen peroxide, used in bleaching. While previous studies have measured the amount of hydrogen produced during geological faulting, CERBERUS focuses on the other side of the equation - what happens to the oxidants? Through initial experiments we show that these oxidants are likely only being released from minerals at very hot temperatures where only the most heat-loving microorganisms, known as hyperthermophiles, can live and thrive, at temperatures close to or over the boiling point of water. From studies back-tracing particular genes common to all life to a Last Universal Common Ancestor (LUCA) we know that such heat-living microorganisms were likely to have been the first life to arise on Earth, and that they used hydrogen. However, the gene back-tracing has also suggested that LUCA contained abundant mechanisms for dealing with oxygen and hydrogen peroxide, while some of the most deeply rooted braches of the 'universal tree of life' contain oxygen utilizing microorganisms. To date, the most widely accepted reason for these oxygen-utilizing genes is that they result from later genetic 'contamination' of all life after the oxygen-producing photosynthesis evolved on our planet, many hundreds of millions of years after life first started. In CERBERUS, we suggest an alternative. That life first arose in hot, subsurface fractures where there was not only hydrogen present, but also hydrogen peroxide produced from water splitting on fractured rock surfaces. We further suggest that these microorganisms evolved key enzymes to combat these oxidants, including those that could convert the more toxic hydrogen peroxide to less toxic oxygen - and in doing so generate usable energy to power life and drive further evolution. CERBERUS will carry out new experiments, measuring how both hydrogen and oxidants are produced in fractured rock-water reactions up to and beyond the known limit of current life (122 deg C). To some experiments we will add pure strains of hyperthermophilic microorganisms, to see how they can alter the products of the reactions, and to see if they can grow from the hydrogen, hydrogen peroxide and oxygen produced during the reactions. Results from CERBERUS should shine a light on how life can survive in the Earth's deep, hot subsurface - and give insight into how early life took hold on our planet.

Background Migrant women in the UK experience inequalities in health and wellbeing and in particular, their experiences of pregnancy and childbirth. Roma women from Central and Eastern Europe suffer barriers to healthcare in their original countries and across Europe contributing to a lack of engagement with health services. Further, like other migrant women, they are often unaccustomed to the way health services work in the UK. Language and cultural barriers, racial bias and discrimination also exist, leading to low uptake of antenatal care. This study aims to address this issue by creating a co-designed accessible antenatal care community information resource with a group of these women, through understanding their needs and preferences regarding existing antenatal care information, to inform design considerations for an evolving prototype of an antenatal care information resource. Objectives To explore with a group of Roma women, their experiences of healthcare services and cultural beliefs about pregnancy and childbirth To work with them to assess the accessibility and acceptability of a range of available antenatal information resources selected following a review of resources To explore and discuss options for forms of antenatal care information for example digital resources catering specifically to their needs To co-create a low-resolution paper prototype of a community-based antenatal care information resource that meets their needs Methods Months 1-2: Scoping review on Roma women's maternity needs, and?review of publicly accessible antenatal information resources to produce a selection for the women to consider Months 3-5: A series of up to eight 2-hour community participatory workshops using design-based participatory methods with Roma women will discuss engagement with health and social care, home remedies, diet and exercise during pregnancy, the effects of smoking and alcohol, and pregnancy-related health problems, to identify issues and gaps in their knowledge. An account of the evidence pathway is provided through audio and visual data collection methods. Months 6-8: Qualitative analysis and project report writing, culminating in a stakeholder engagement workshop, to determine scalability with project advisory group, with potential transferable insights to other marginalised newly arrived groups of migrant women. Outcomes: a) design considerations presented alongside the co-designed prototype for an antenatal care information resource, b) final design to be scaled up, piloted and evaluated with the wider Roma community of women, c) an inclusive and participatory approach for best practice that can be replicated with other marginalised groups of migrant communities, e) improved perinatal and maternal outcomes for Roma women.

Pharmaceuticals have developed via three manufacturing revolutions. The first arose in the 19th century from the ability to chemically synthesise drugs previously only obtainable from natural sources (aspirin, quinine). Next in the 1970's the biotechnology revolution enabled proteins such as insulin, clotting factors or antibodies to be developed into safe widespread treatments. Currently we are in the midst of the cell therapy revolution where the ability to grow human cells outside the body is being exploited to create cell based treatments. More generally, artificial cell culture is a widespread and rapidly expanding technology with applications in medicine, bioprocessing, crop science, drug development and clinical research. In recent years the idea of cell based therapies has moved from mere possibility to actual treatments for conditions such as leukaemia, stroke, blindness and arthritis. These require not only that cells can be grown outside the body but that they can be multiplied and modified before reintroduction into the patient. In many cases the body's immune system restricts cell therapies to autologous forms where the original cells are obtained from the patient, grown and or modified and then reintroduced. However several allogeneic treatments, where a commercial cell line is used to treat many patients, are also in development for conditions such as stroke or inherited blindness. Much work depends upon growing stem cells which are a "raw material" that can be transformed into a wide range of tissue types for medical applications. Growing sufficient numbers of stem cells to satisfy the needs of various treatments is still a significant challenge. Cells used in research laboratories are often selected for their ability to grow rapidly and indefinitely on plastic surfaces but cells for therapy need life like environments and grow in a highly regulated manner. Currently, cells are cultured on surfaces that largely fall into two groups; low cost, bulk materials, exemplified by plastic dishes, or high cost, low volume biological matrices which recreate the conditions found within the body and are increasingly important as more demanding or fragile cell types are used. This project seeks to use a recently developed and patented industrial process to overturn this product landscape by manufacturing engineered protein polymers with advanced cellular functions at low cost. By bridging the gap between traditional polymer science and protein biochemistry we can create a range of matrices to assist the growth of cells for many downstream applications. The 18 month project, supported by the Cell and Gene Therapy Catapult will start by developing one lead product for use in the rapidly expanding stem cell industry. This uses simple coating of plastic surfaces by our protein polymer and has already shown significant advantages over rival technologies in stem cell culture in our hands. Independent validation will enable us to embark on its commercial exploitation to reduce costs and increase efficiency of the whole cell therapy sector. We then intend to further demonstrate its wider applicability for work on muscle, nerve and cartilage by collaboration with leading research groups in the field and with industry. We will also test its usefulness in recreating even more realistic 3 dimensional environments for cell and tissue culture. Finally by exploiting a recent development by us to include large protein modules within the polymer we will create a matrix which can be decorated with any number of cell modifying molecules which are found in natural extracellular environment. This offers an unprecedented opportunity to create bespoke complex cell growth environments in the "test tube" Using both readily commercialisable products and the new intellectual property we intend to move decisively toward either spin out company or licensing agreement at the end of this project.

Rufopoly is a participatory learning board game enabling players to undertake a journey through a fictitious rural urban fringe called RUFshire, answering questions and making decisions on development challenges and place-making; those answers then inform each player's vision for RUFshire. The encountered questions are determined by the roll of a die and based on primary data collected for a Relu project (2010-2012) about Managing Environmental Change at the Rural Urban Fringe. Rufopoly has been used extensively in early stages of projects and plans such as the pioneering Greater Birmingham and Solihull Local Enterprise Partnership spatial plan and has been used by government, EU project groups, local authorities, business, community groups, universities and schools. It has exposed audiences to issues associated with the delivery and trade-offs associated with planning and environmental issues at the fringe but crucially without the use of complex jargon. We believe that the full potential and impact of Rufopoly has yet to be fully realised. There are several reasons for this: 1. Rufopoly was developed towards the end of our Relu project as an unplanned output for a conference run by Relu in 2011 on 'Who Should run the Countryside?'. Its success prompted its inclusion as an output. 2. There were insufficient funds for it to be successfully tested and integrated with policy and practice communities to maximise its utility as a learning tool as this was never the original intention of the project. 3. It is currently presented as a one size fits all board game of a hypothetical place. More time is needed to explore the potential of Rufopoly to become a generic platform for stakeholders wishing to develop their own versions of the tool to meet their own needs and to fill a widely recognised gap in the effectiveness of participatory tools for improved decsion making. This knowledge exchange project addresses these deficiencies by drawing together the shared knowledge and previous experiences of designers and users of Rufopoly. This informs a series of interactive workshops in Wales, England and Scotland to identify how this kind of game-format can be enhanced into a more effective and multifunctional tool. This will help extend and embed the impact for a range of policy and practice partners in the form of a Rufopoly Resource Kit. By working collaboratively with end users we can identify how Rufopoly can be reconfigured across different user groups and organisations in tune with their agendas and needs. There are four stages to this project: WP1: Review and learn lessons from previous Rufopoly experiences. This involves (1) an assessment of the actual results and findings from past games that were written up and the results analysed. (2) critical assessments of the strengths and weaknesses of Rufopoly from facilitators and core participants. We will draw priamirly from our UK experiences but are also able to secure insights from the international adaptations of Rufopoly from Nebraska (November 2013) and Sweden (2014). WP2: Conduct a series of interactive workshops with different policy and practice audiences. These workshops will be held in England, Scotland and Wales using members of the research team and other participants. The purpose of these workshops is to (1) share results of WP1; (2) assess how the tool could be reconfigured to address the principla needs and challenges facing participants; and (3) prioritise feasible options for a Rufopoly Resource Kit. WP3: Using WP1 and WP2 outcomes, we will design and trial (across our team) the Rufopoly 'Mk2' resource kit and associated materials/guidance. WP4: Launch the Rufopoly Resource Kit and guidance in a live streamed global workshop event. This would; reveal the basic resource kit as co-designed by the team and enable testers of the resource kit to share their experiences maximising knowledge exchange and its range of potential applications.

Strongly associated with the epidemics of obesity and type 2 diabetes mellitus (T2DM) that are testing healthcare systems worldwide, Non-Alcoholic Fatty Liver Disease (NAFLD) is an increasingly common cause of advanced liver disease in the aging population of Europe. NAFLD is a spectrum of hepatic fat accumulation (steatosis); steatosis plus inflammation (non-alcoholic steatohepatitis, NASH); fibrosis/cirrhosis; and hepatocellular carcinoma in the absence of high alcohol consumption. Up to 30% of the EU population have NAFLD, which will be the main aetiology underlying liver transplants by 2020. However, NAFLD is characterized by substantial inter-patient variability in severity and rate of progression. What determines this is unknown. A large population is at risk, but only some experience morbidity. NAFLD severity is currently best assessed by liver biopsy, an invasive, costly and risky procedure - factors that hinder treatment. There is a need to understand the biological and environmental factors that drive inter-patient variability and to develop robust and more acceptable methods for diagnosis, risk stratification and therapy so that effective medical care may be targeted to those that will benefit most. The overall EPoS concept is that improved understanding of pathogenic processes and drivers of disease progression will best be achieved when multiple ‘omics’ approaches are applied to a single cohort of patients to build a multi-dimensional record of how systems are perturbed across the entire spectrum of disease. NAFLD sits at the intersection of key biological processes: carbohydrate/lipid homeostasis, immune/inflammatory activation, wound healing/fibrosis and cancer biology. Once completed, EPoS promises to deliver a substantial and definitive atlas of pathophysiological variation across a spectrum of progressive liver disease. Translation of these findings will therefore impact on closely related pathologies including T2DM and cardiovascular disease.