The aim of the research is to develop novel approaches for the analysis of biomolecules, and in particular proteins, directly from their natural (or actual) environment, i.e., to develop approaches for in situ biomolecular analysis. Proteins are the work-horses of the cell and perform all the functions required for life. They also find uses as therapeutics and in consumer products. To gain insight into the various and specific roles of proteins in life processes, or to determine the therapeutic efficacy of protein drugs, or to establish the environmental fate of protein additives in consumer products, it is necessary to be able to analyse proteins at a molecular level. Mass spectrometry, in which ionised molecules are characterised according to their mass-to-charge, is ideally suited to this challenge, offering high sensitivity, broad specificity (all molecules have a mass), and the capability for chemical structure elucidation. The ultimate goal is to link molecular analysis directly to molecular environment. Much like a forensics officer tasked with determining the presence of an illicit substance, there is much greater reliability and credibility afforded to an analysis performed at the scene of the crime than to one performed following removal of the sample to a separate location and alternative surroundings. Growing evidence suggests in situ protein analysis has groundbreaking roles to play in biomarker discovery, diagnosis & early detection of disease, targeting therapeutics (personalised medicine) and assessment of therapeutic efficacy. The benefits of in situ protein analysis can be illustrated by considering a thin tissue section through a drug-treated tumour. In principle, in situ analysis would inform on drug-target interactions (i.e., is the drug binding to the correct protein?). Moreover, with in situ protein analysis the capacity for artefact introduction as a result of sample preparation (e.g., application of a matrix) or sample damage is eliminated. Nevertheless, a number of challenges exist. Proteins are large molecules associated with a vast array of chemical modifications, and which form loosely-bound complexes with themselves, other proteins and other molecule types. It is not only their chemical structure but also their overall 3-D structure which dictate their function. Other molecular classes that are hugely important in biological processes also have an intricate relationship with proteins. Any in situ mass spectrometry approach needs to be able to meet these analyte-driven challenges, i.e., it must be capable of (a) measuring proteins and characterising any modifications, (b) detecting protein complexes and determining their constituents, (c) providing information on 3-D structure, and (d) detecting other relevant molecular classes. Moreover, there are technique-driven challenges for in situ analysis including inherently high sample complexity and wide ranging concentrations, and opportunities for quantitation. The research will meet these challenges by developing a newly emerging in situ approach, liquid extraction surface analysis mass spectrometry, in combination with two complementary types of ion mobility spectrometry (which can either provide information on 3-D structure, or separate ionised molecules in the mass spectrometer on the basis of their 3-D shape) and a structural elucidation strategy known as electron-mediated dissociation mass spectrometry. The research will be undertaken primarily at the University of Birmingham in the Advanced Mass Spectrometry Facility in the School of Biosciences and the School of Chemistry mass spectrometry facility. The programme involves a number of academic and industrial collaborators and additional research will be carried out during scientific visits to National Physical Laboratory (NPL), Thermo Fisher Scientific, Waters, Owlstone, Florida State University, Texas A&M University and Université d'Aix-Marseille.

The global hydrogen generation market is valued at $115.25 billion in 2017 and is projected to grow to $154.74 billion by 2022 [Global Outlook & Trends for Hydrogen, IEA, 2017]. We are witnessing significant market opportunities emerging for hydrogen technologies today. New and existing hydrogen technology developments and market activities are projected to intensify over the coming decade. Sustainable hydrogen solutions are a key pathway for decarbonising transport, heat and power generation sectors. Common challenges to sustainable hydrogen being adopted across these sectors are: - Cost reduction - Safety - Systems level and multisectoral innovations - Managing change Over the next decade innovative solutions are needed to tackle the above challenges, but it will be impossible without a dedicated mechanism to train doctoral Energy Innovation Leaders. These leaders should have a firm grasp of the technology from scientific fundamentals through to applied engineering and a solid understanding of the techno-economic barriers and an appreciation of the societal issues that will impact on the translation of disruptive technologies from research labs through to market. This goes beyond being multidisciplinary, but is a transdisciplinary training, reflecting the translation steps from understanding market driven needs, planning and conducting appropriate basic and applied research to products/solutions/system development through to successful market penetration. This is delivered by a cohort training approach through the cross fertilisation of ideas of a cohort with a diverse background, peer-demonstration of the value of research across a diverse range of stakeholder-led projects, thus facilitating a peer-to-peer transdisciplinary learning culture. The SusHy Consortium, led by Gavin Walker, continues a long running and highly successful collaboration in hydrogen research between the Universities of Nottingham, Loughborough, and Birmingham (UoN, LU, UoB) which started over a decade ago with the Midlands Energy Consortium. The Midlands Energy Graduate School spawned two successful CDTs (Hydrogen, Fuel Cells and their Applications and the current Fuel Cells and their Fuels). The current proposal for a CDT in Sustainable Hydrogen brings together the world leading expertise in hydrogen generation, purification, sensors/monitoring, and storage, along with whole systems issues (resilience engineering, business economic models and life cycle analysis) which exist across the three Universities. A gap in the consortium expertise is in the research field of hydrogen safety and we identified the internationally-renowned Hydrogen Safety Engineering and Research Centre (HySAFER) at Ulster University (UU) as the right partner to deliver on this key aspect. This is the first broad collaboration in the world seeking to investigate, train researchers and produce leaders in Sustainable Hydrogen. Stakeholder Partnerships. A key strength of this CDT is the active involvement of the Stakeholders in co-creation of the training programme which is reciprocated in the value with which the Stakeholders view of the CDT. This shared vision of a training partnership between the Universities and Stakeholders will lead to the smooth function of the CDT with not just a high-quality training programme, but a programme that is tailored to the sector needs for high-quality, industry-ready doctoral Energy Innovation Leaders. The valued CDT-stakeholder partnership will also be a significant appeal to candidates interested in energy-related PhDs and will be used to help market the CDT programme to a diverse talent pool.

Our vision is to establish the East Midlands Breathomics Pathology Node (EMBER) as a centre-of-excellence to ensure the development of novel breath analysis tests to help understand disease processes and clinical decision making. This will help develop new ways to improve the way we can chose the right treatment for the right patient. Measuring breath is familar to us all in the setting of the breathalyser to detect alcohol levels, but perhaps less well known is that exhaled breath contains lots of substances known as volatile organic compounds (VOCs) derived from the lung itself and from more distant organs. Recent advances in technology allow the pattern and quantity of these VOCs to be measured rapidly in patients in hospital, the doctors clinic and potentially at home. The patterns of these substances varies between diseases and can distinguish between different types of the same condition. The range of clinical conditions for which breath tests could be useful is very large. EMBER will intially focus upon respiratory infections, lung cancer, chronic respiratory disease such as asthma and chronic obstructive pulmonary disease, and cardiovascular disorders such as heart failure. The main barrier to advancing breath analysis as a routine test is that its development requires bringing together a large multi-disciplinary team of scientists and clinicans that are experts in breath analysis to work with the NHS, industry and patients to make these ideas a reality. The East Midlands has a unique and congruent group of clinical and analytical researchers drawn from the University of Leicester (UoL), the University Hospitals of Leicester NHS Trust (UHL) and Loughborough University (LU) with strengths in clinical research, analytical chemistry, data management and mathematical analysis of complex data. EMBER will focus these combined strengths, and co-ordinates existing collaborations with industry partners to create a nationally-leading centre in breath analysis with the critical mass to establish world-class delivery of new technology to the clinic, and training today's and the future scientists and health care professionals. EMBER will deliver near-patient and remote sensing technologies to analyse breath. We shall rigorously test these technologies in different diseases and in different health care settings such as acute hospitals, secondary and primary care and in the home. We shall include vulnerable patient groups such as the elderly with complicated multiple diseases and children in whom blood tests are more challenging. EMBER will ensure the usefulness of these tests so that their application brings economic and health benefits by helping to make the right decisions in choosing the right treatment for patients.