Life expectancy globally and in the UK has increased and this brings many health-related challenges, including how best to support and maintain health in older people. Ageing affects every organ in our body, including our skin. As we age, the function of our skin declines; it becomes more fragile, its strength and resilience are reduced and, when challenged, it is less able to repair any damage. These changes can lead to increased susceptibility to infections and wounds that fail to heal, and, overall, can reduce the quality of life of older people. The epidermis is the outer layer of our skin and is the major barrier between the body and the environment. With increasing age, the structure of the epidermis alters and we observe specific changes to the outermost epidermal layer, the stratum corneum, the structure essential to conserve water. This 'waterproof' layer consists of specialist fats (called lipids) arranged to provide its correct structure and function. Age-related changes to lipids within the stratum corneum have a significant impact upon the properties of the epidermis. Although age-related skin changes occur in both men and women, the impact of ageing is understood better in women, where it has been studied in association with the menopause. We believe that understanding when age-related skin changes occur in both genders is essential to provide important new knowledge, which will allow us to provide guidance and plan interventions to protect and strengthen the aged skin, helping to maintain its healthy function. In this project we will explore the hypothesis that fundamental changes in the lipid content of the epidermis, particularly within the stratum corneum, can influence the behaviour of the skin with increasing age and, in females, this is initiated at menopause. In undertaking this project, we aim to discover when these age-related changes start to occur in both men and women, and to understand the molecular mechanisms that are involved in the age-related decline of skin function. We also want to explore nutritional interventions that can support skin health as we age. Our research has three key objectives: 1. To discover at what age we begin to see changes in how skin functions (its strength and resilience) and in the lipid composition of the epidermis, in healthy men and women. 2. To understand how epidermal cells, called keratinocytes, from the skin of young and old, men and women, can uptake and metabolise lipids needed to maintain the correct composition, structure and function of the stratum corneum. 3. To explore whether dietary supplementation with polyunsaturated fatty acids can improve skin's strength and resilience, its lipid composition, and its ability to repair the epidermis in older healthy human subjects. The proposed research will show for the first time the chronological sequence of events that control the decline of epidermal function with increased age, and, at the same time, allow a direct comparison of skin properties between men and women of the same age. Furthermore, the research will reveal fundamental information on the ability of aged keratinocytes to use important dietary lipids. By using a simple dietary intervention, we will discover whether lipid fortification results in the formation of a stronger stratum corneum, better able to withstand challenges and/or have improved capacity for repair. Obtaining these valuable mechanistic insights into the biology of aged skin will provide an opportunity to develop preventative measures, and support the development of bespoke nutritional supplements to address the specific needs of aged skin, with ultimate aim of maintaining skin health in later life.

Human beings have always worried about ageing, with special worry reserved for premature ageing. Consequently, we have tried numerous different methods to try and achieve rejuvenation - a state of renewed youth or the appearance of youth. The everyday methods with which we are perhaps most familiar - skin care products, dietary and exercise regimes - have long histories but were transformed in the decades following the First World War, when a wealth of scientific research and new anti-ageing products appeared to promise the ability to prolong youthfulness, fertility and vitality. This Fellowship sets out to examine the impact of the most widespread methods of rejuvenation - injection and application of hormones, using electricity on the body, skincare products, specific diets and exercise regimes - on post-WWI Britain. We already know from previous historical work that the unique socio-political context of interwar Germany precipitated the rise of eugenic ideals about race and biology, as well as beauty and ugliness, whilst at the same time the rising consumer-culture context of the United States enthusiastically embraced technological and scientific developments linked to human ageing. However, Britain in this period has remained largely unstudied, and consequently we risk overstating the significance of developments elsewhere. Concerns about the overall fitness (and fertility) of the population were increased by Britain's participation in the two World Wars, and it is clear that the perceived need for rejuvenation of both individuals and society became a topic of intense debate both in medical and scientific circles and in the wider public sphere. Especially prior to the NHS, manufacturers and entrepreneurs attempted to exploit this fascination, and they claimed that a number of existing therapies had rejuvenating properties, as well as trying to introduce new devices and products. The domestication of electrical lighting and the increasingly wide reach of cinema and photography also placed added pressure on the British public, and particularly women, to look at their best. The Fellowship will explore why rejuvenation was such a prominent matter of public interest in this period, and it will show in what ways the methods used to slow, stop or even reverse ageing helped to define some of the most fundamental elements of what it means to be human. The principal goals are to (i) explain the diversity of approaches to rejuvenation, (ii) examine the different advertising and marketing strategies and their relationship with contemporary scientific perspectives on ageing, and (iii) uncover how everyday habits were changed by anti-ageing products, procedures and lifestyles. Allied to this, the Fellowship will explain how manufacturers of rejuvenation preparations and devices attempted to convince British publics of the efficacy of their products, and show to what extent the target audiences of these products were persuaded by such claims. The Fellowship seeks to explain how and why this period in Britain became such a fruitful environment for different rejuvenation strategies. Drawing on a wide range of archival materials, including the papers of manufacturers and retailers of rejuvenation-related products (such as Boots, Pond's and Elizabeth Arden), newspaper and periodical sources, objects, specialist scientific and medical texts, personal accounts and fictional representations of rejuvenation, the project will link together histories of the body, ageing, the limits of biomedical explanation, everyday medical practice, the impact of global conflict on health and wellbeing, and the medical marketplace, amongst other themes. The Fellowship will consequently deepen our understanding of the historical body and the human condition by demonstrating that ageing and rejuvenation were intimately connected with a wide range of medial, social, cultural and economic factors, including beauty, gender, class, race, warfare, and eugenics.

It is now clear that our health depends largely on the microbes that exist in and on our bodies i.e. the microbiome. Skin is no exception and we now know that bacteria living on our skin provide us with many essential functions such as combatting infections and helping to enhance the role of skin as a barrier. The skin and its microbiome are unique in that they are regularly exposed to sunlight. For a long time it has been known that sunlight can damage the DNA of skin cells. DNA damage is associated with 'sunburn' which is perhaps, along with tanning, the most well known response of skin to sunlight. However, even exposure which does not cause a sunburn can be sufficient to damage DNA but usually, the skin cells are able to repair this damage very quickly. However, any damage that is too bad to repair is dealt with by the cells undergoing a process called 'apoptosis' which is a very controlled way of the cells dying. This process is essential to stop cells with damaged DNA from multiplying and is part of the skin's defence against forming tumours. How exposure to sunlight affects our skin microbiome is not really known. However, we have shown that there is a particular bacterium on our skin which promotes apoptosis in skin cells that have been exposed to sunlight. This bacterium does this by producing a molecule in response to sunlight that induces apoptosis in skin cells. This shows that our skin microbiome produces molecules that alter how our skin cells work following sunlight exposure. In this project we will be investigating this more. Our first question is: 'Does the presence of the microbiome affect the sunburn response in humans?'. We will answer this by removing the microbiome (by cleaning with alcohol) from an area of skin in 10 volunteers and then exposing them to several doses of 'simulated sunlight'. We will be looking at how the sunburn develops in areas of skin without the microbiome compared to with the microbiome. We will take a 'biopsy' - a small piece of their skin which has been sunlight exposed and we will perform experiments in the laboratory to determine whether cells in this piece of skin have undergone apoptosis. Successful completion of this work will answer a fundamental question as to the role of the skin microbiome in the sunburn response in humans. Our second question relates to the molecule produced by the bacterium that promotes apoptosis. At present we have data as to its effects in isolated skin cells. We now want to look at this in actual skin. We are able to obtain skin from elective plastic surgery procedures and we have methods already established to keep this skin 'alive' in the laboratory. We will be using this to investigate the effects of the molecule in real human skin. We also aim to purify the molecule from the bacterium and try to identify what it is. We will also be studying how the molecule causes apoptosis in skin cells. Successful completion of this work will shed light on the possible role of bacteria in protecting skin against the multiplication of damaged skin cells. Our final question is: 'Are there other bacteria in the skin microbiome that can protect against DNA damage following exposure to sunlight or promote DNA repair?'. We have already (in a previous project) isolated over 150 types of bacteria from healthy humans. We will be testing these bacteria to find out whether any of them can reduce DNA damage or speed up repair of damaged DNA. Successful completion of this work will identify bacteria that could be used as novel sunscreens or 'after sun' treatments for skin. This project benefits from having Walgreen Boots Alliance (aka 'Boots the Chemist') and Croda PLC (a global leader in the manufacture of speciality chemicals) as project partners. A better understanding of the ways in which the microbiome protects skin against sunlight will be beneficial in helping these project partners develop new ways to help consumers protect their skin.

Digital technology opens up a new era in the understanding of human behaviour and lifestyle choices, with people's daily activities and habits leaving 'footprints' in their digital records. For example, when we buy goods in supermarkets and use loyalty cards to obtain benefits (e.g., future discounts), the supermarket records our purchases and creates a representation of our habits and preferences. Until now the use of 'digital footprint' data has mostly been limited to private companies. Companies have been using aggregates of these data to track sales of their products, to understand the factors that impact sales levels, and to target marketing and promotions. Changes in Data Protection law in the UK, i.e. General Data Protection Regulation, mean the public can now access and donate their data for academic research. Shopping history data, recorded through loyalty cards by retailers, are an extremely useful source of information for population health research as it can provide granular, objective data on real world choices and behaviours (e.g. painkillers, food) and other behaviours (e.g., pain and weight, wellbeing management). This information is often hard to obtain in the health research domain. Links between lifestyle choices and health outcomes are commonly studied through self-report questionnaires that ask people to remember their everyday choices and behaviours, which can bias results: responses about behaviours do not always reflect the reality of what people actually do. If and when shopping history data are used in a privacy preserving and ethical manner, these data can be utilised for public good, benefiting health research (e.g., helping to understand how everyday behaviours and lifestyle choices impact health and social outcomes). For example, what are the exact levels of alcohol consumption that lead to irreversible health damage for unborn babies accounting for moderating factors (e.g., age, gender, genetic makeup, etc.)? Under which conditions do different types of ready meals contribute to obesity? Do chemicals in household products lead to higher risks of cancer and other adverse health outcomes in children? The Transaction Data for Population Health research programme utilises commercially collected datasets for privacy-preserving, ethical research to benefit the public good. This program questions whether shopping history data can be used in a positive way to support health research and the development of new interventions. The fellowship will establish the feasibility of novel ways of assessing both health outcomes and associated lifestyle choices through objective measures of real world behaviours reflected in retail shopping history data recorded through loyalty cards. At the same time it will build a framework that can be used by future researchers. My research programme in Yrs 1-4 will unfold in three stages. First, it will use commercially collected datasets to identify and study reproductive health outcomes through patterns in the shopping data. Second, it will validate patterns in the data which are associated with health outcomes using established Longitudinal Population Studies such as the Avon Longitudinal Study of Parents And Children (aka Children of the 90s). Third, I will use the linked datasets to research questions of population health importance in the domain of reproductive health, such as what are the true rates of miscarriages, how do women manage postpartum health and wellbeing, whether breastfeeding is better in the long run for children's mental health, and others. This will be done through studies with Children of the 90s participants and the general public helping to validate the results. The impact of the project will realised in Yrs 5-7 and include a conceptual change in techniques for studying population health, making it possible to identify lifestyle causes of diseases, assess the impact of national policies, and provide recommendations for health interventions.

This user-need CDT will equip graduates with the skills needed by the UK formulation industry to manufacture the next generation of formulated products at net zero, addressing the decarbonisation needs for the sector and aligning with this EPSRC priority. Formulated products, including foods, battery electrodes, pharmaceuticals, paints, catalysts, structured ceramics, thin films and coatings, cosmetics, detergents and agrochemicals, are central to UK prosperity (sector size > £95bn GVA in 2021) and Formulation Engineering is concerned with the design and manufacture of these products whose effectiveness is determined by the microstructure of the material. Containing complex soft materials: structured solids, soft solids or structured liquids, whose nano- to micro-scale physical and chemical structures are highly process dependent and critical to product function, their manufacture poses common challenges across different industry sectors. Moving towards Net Zero manufacture thus needs systems thinking underpinned by interdisciplinary understanding of chemistry, processing and materials science pioneered by the CDT for Formulation Engineering at the University of Birmingham over the past twenty years, with a proven delivery of industrial impact evidenced by our partner's letters of support and three Impact Case Studies ranked at 4* in the recent Research Excellence Framework in 2021. A new CDT strategy has been co-created with our industry partners, where we address new user-led research challenges through our theme of Formulation for Net Zero ('FFN0), articulated in two research areas: 'Manufacturing Net Zero (MN0)', and 'Towards 4.0rmulation'. Formulation engineering is not taught in first degree courses, so training is needed to develop the future leaders in this area. This was the industry need that led to the creation of the CDT in Formulation Engineering, based within the School of Chemical Engineering at Birmingham. The CDT leads the field: we won for the University one of the 2011 Diamond Jubilee Queen's Anniversary Prizes, demonstrating the highest national excellence. The UK is a world-leader in Formulation; many multinational formulation companies base research and manufacture in the UK, and the supply of trained graduates, and open innovation research partnerships facilitated by the CDT are critical to their success. The CDT receives significant industry funding (>£650k pa), supported by 31 industry partners including multinationals: P&G, Colgate, Unilever, Diageo, Devro, Fonterra, Samworth Bros., Jacobs Douwe Egberts, Nestle, Pepsico, Mondelez, GSK, AZ, Lonza, Novartis, BMS, BASF, Celanese, Croda, Innospec, Linde/BOC, Origen, Imerys, Johnson Matthey, Rolls-Royce/HTRC, JLR Lucideon and SMEs: Aquapak, CALGAVIN and ITS/StreamSensing. Intra and cross cohort training is central to our strategy, through our taught programme and twice-yearly internal conferences, industry partner-led regional research meetings, student-led technical and soft skills workshops and social events and inter CDT meetings. We have embedded diversity and inclusion into all of our projects and processes, including blind CV recruitment. Since 2018 our cohorts have been > 50% female and >35% BAME. We will co-create training and research partnerships with other CDTs, Catapult Centres, and industry, and train at least 50 EngD and PhD graduates with the skills needed to enhance the UK's leading international position in this critical area. The taught programme delivers a common foundation in formulation engineering, specialist technical training, modules on business, entrepreneurship and soft skills including a course in Responsible Research in Formulation. We have obtained promises of significant industry and University funding, with 67 offers of projects already. EPSRC costs will be 44% of the cash total for the CDT, and ca. £27% of the whole cost when industry in-kind funding is included.