CONTEXT: At the forefront of biological research is understanding how cells interact with their environment. Selective interaction with the extracellular milieu and the recognition of molecular signatures presented on a cell surface enables organisms to respond to environmental changes, which is often altered in disease states. Many cell targeting molecules are advancing our understanding of how these interactions influence different cell phenotypes. However, distinct challenges in the development of these targeting molecules (e.g., small molecules, antibodies, aptamers) necessitates the need for innovative bioanalytical infrastructure to dissect and characterise their binding profile in live cells. AIMS & OBJECTIVES: The purpose of this equipment grant is to establish the UK's first Real-Time Interaction Cytometry (RT-IC) facility, which will enable users to measure the binding properties of molecules (e.g., kinetic rates; affinity, avidity) directly on live cells. The Glas-cyto facility will be part of Glasgow's wider biophysical centre of excellence formed between the Universities of Strathclyde (UoS) and Glasgow (UoG), enabling the UK userbase integrated access to a breadth of bioanalytical and biophysical facilities to examine cellular binding interactions. The heliXcyto equipment will be suitable for a wide range of analyses for eukaryotic cell types and will be underpinned by support from dedicated research technical professionals (RTPs) within the Strathclyde Centre for Molecular Bioscience (UoS) and the Integrated Protein Analysis Facility (UoG). THE RESEARCH THAT THE EQUIPMENT WILL ENABLE: Our dedicated facility will enable users the unique opportunity to culture live cells alongside instrumentation that will quantify binding interactions in less than 30 min. Access to such a facility will enable our user base to develop better cell-targeting biologics (e.g., antibodies, aptamers, Theme 1), deliver a new design proxy for the development of cell targeting molecules for the development of diagnostic platforms (Theme 2), and further our understanding of protein trafficking and cell-selective recognition of G-protein coupled receptors by small molecules (Theme 3). POTENTIAL APPLICATIONS & BENEFITS: The current state-of-the-art in the biophysical analysis of extracellular interactions have predominantly focused on low throughput assays (e.g., CETSA, In Cell Pulse DiscoverX, SPR), which require the downstream isolation of analytes, or qualitative analysis of interactions by flow cytometry. The major drawback of these techniques is that binding is inferred rather than quantified. Detailed quantitative knowledge of spatial patterns of receptor expression, and reconciling these data with binding interactions can accelerate the translational potential of novel targeting molecules in early discovery. Establishing this dedicated facility within Glasgow will provide, for the first time, the ability to quantify binding interactions on live cells, under conditions more closely mimicking their native environment. The Glas-cyto facility will enable new training opportunities across the breadth of the UK's biological user base, and infrastructure to enhance interactions with industrial partners.

We will establish a technology platform that changes the way we diagnose and treat patients. It involves detecting and producing nano-sized biological particles that act as communication machinery in nature. These particles are called exosomes and with significant investment in the engineering required to accurately capture and profile them, it will be possible to create a new class of diagnostics that can detect disease earlier than is currently possible, based on the release and detection of specific exosomes. It will also be possible to distinguish between different stages of disease, which will help to tailor the right treatment to an individual patient. The diagnostics platform will also form the basis for manufacturing analytics that will enable cell and gene therapies to be carefully monitoring during manufacture. Cell and gene therapies currently cost in the order of £100,000 to £1,000,000 per dose and is related to the fact that bioprocesses (the manufacturing approaches used to create them) are sub-optimal. A radical advance in manufacturing analytics will help to better monitor and control manufacturing, which will lead to improved product consistency and ultimately drive down cost of manufacturing, which will catalyse the routine adoption of cell and gene therapies in the NHS. Finally, by producing exosomes using industrial bioprocesses it will be possible to create new drugs based on exosomes, exploiting their communication machinery to target therapies to sites of disease. This will involve a combination of engineering exosomes to have increased potency, or loading them with powerful drugs and targeting them directly at the diseased tissue. Ultimately, this will radically advance personalised medicine across diagnostics, analytics and drug delivery. In 30 years' time this technology platform will be widely used in healthcare to diagnose and treat disease with high fidelity using bespoke formulations. In order to advance this vision, phase 1 feasibility studies will address engineering challenges in sensor development to detect exosomes at different orders of sensitivity. It will also address the consistent production of exosomes at pilot scale in order to advance the exosome therapeutic platform.

We will establish a technology platform that changes the way we diagnose and treat patients. It involves detecting and producing nano-sized biological particles that act as communication machinery in nature. These particles are called exosomes and with significant investment in the engineering required to accurately capture and profile them, it will be possible to create a new class of diagnostics that can detect disease earlier than is currently possible, based on the release and detection of specific exosomes. It will also be possible to distinguish between different stages of disease, which will help to tailor the right treatment to an individual patient. The diagnostics platform will also form the basis for manufacturing analytics that will enable cell and gene therapies to be carefully monitoring during manufacture. Cell and gene therapies currently cost in the order of £100,000 to £1,000,000 per dose and is related to the fact that bioprocesses (the manufacturing approaches used to create them) are sub-optimal. A radical advance in manufacturing analytics will help to better monitor and control manufacturing, which will lead to improved product consistency and ultimately drive down cost of manufacturing, which will catalyse the routine adoption of cell and gene therapies in the NHS. Finally, by producing exosomes using industrial bioprocesses it will be possible to create new drugs based on exosomes, exploiting their communication machinery to target therapies to sites of disease. This will involve a combination of engineering exosomes to have increased potency, or loading them with powerful drugs and targeting them directly at the diseased tissue. Ultimately, this will radically advance personalised medicine across diagnostics, analytics and drug delivery. In 30 years' time this technology platform will be widely used in healthcare to diagnose and treat disease with high fidelity using bespoke formulations. In order to advance this vision, phase 1 feasibility studies will address engineering challenges in sensor development to detect exosomes at different orders of sensitivity. It will also address the consistent production of exosomes at pilot scale in order to advance the exosome therapeutic platform.

AMR is a global threat needing urgent coordinated actions via a transdisciplinary approach with pooling of resources and research efforts to expedite practical solutions for new - diagnostics, therapies and vaccines - the three lines of defence against AMR. In 2016, the O'Neill report 'analysed the global problem of rising drug resistance and proposed concrete actions'. However, almost a decade later, without 'fit-for-purpose' diagnostics, the report's recommendation of diagnostics-guided antimicrobial treatments by 2020 remains unrealistic even today. In addition, to have a meaningful impact in controlling AMR, One Health approach is crucial for all AMR interventions including diagnostics - as emergence and spread of AMR is interlinked between humans, animals, plants and the environment. Animals raised for food account for 73% of global antimicrobial use, and >75% of human pathogens detected (last 3 decades) have originated in animals, highlighting the context and the need for diagnostics for domesticated animals. Plant health depends heavily on fungicides for the control of fungal and oomycete diseases. However, resistance against multiple fungicide classes has led to control problems in key diseases in wheat, barley, potatoes, and fruits. There are concerns about the impact of agricultural fungicides on antifungal resistance in human pathogens, especially Aspergillus fumigatus. Thus, diagnostics are needed for timely detection to prevent spread. Environment Chemical pollutants, heavy metals, antimicrobials, co-selectors and pathogens and pesticides - all drive selection of AMR, thus needing prompt and precise detection and control. Clinical need for appropriate diagnostics is well-documented. AMR from Bacterial pathogens are associated with ~5 million AMR deaths annually and the threat from fungal pathogens and their resistances are high too. Hence, our Network's focus is One Health diagnostics. While the UK is well-placed to meet the scientific challenges of developing such technologies and become an international leader, a step-change in our approach is needed if we are to transition the country's scientific excellence into a coordinated drive to develop practical solutions that can be implemented and adopted across these sectors. Thus, through a transdisciplinary team, ARREST-AMR will support the successful development and smooth journey of technologies from research labs to adoption and use in 'real life' through 5 objectives: Identify 'needs': Across all the sectors (i) identify areas (such as diseases, pathogens, chemical co-selectors) where the diagnostics are needed the most (ii) what types of technologies are needed (iii) where should they be placed to provide the most useful information at the right time and at the right cost. To achieve this, the Network will conduct extensive stakeholder engagements across all sectors. Innovate: Experts such as scientists, engineers, clinicians, veterinarians, crop-protection professionals, experts in One Health and biologists who work in fundamental biology of AMR - will together develop research projects to contribute to better understanding of AMR, with the knowledge-generation focussed to develop new products that address the 'needs'; and help existing UK technologies improve their diagnostic performance/economic utility and reconcile the 'needs'. Evaluate: Supporting with standardised approaches for performance, economic and utility evidence generation for each sector will engender a culture of translational-focussed research. Implement: We will support translational aspects including Regulatory and behavioural aspects, identifying facilitators and barriers for adoption. Cross-pollinate: Will help exchange of best practices, needs, regulatory aspects and product applications within and outside - their sectors and the Network.

To secure a continued supply of safe, tasty, affordable and functional/healthy proteins while supporting Net Zero goals and future-proofing UK food security, a phased-transition towards low-emission alternative proteins (APs) with a reduced reliance on animal agriculture is imperative. However, population-level access to and acceptance of APs is hindered by a highly complex marketplace challenged by taste, cost, health and safety concerns for consumers, and the fear of diminished livelihoods by farmers. Furthermore, complex regulatory pathways and limited access to affordable and accessible scale-up infrastructure impose challenges for industry and SMEs in particular. Synergistic bridging of the UK's trailblazing science and innovation strengths in AP with manufacturing power is key to realising the UK's ambitious growth potential in AP of £6.8B annually and could create 25,000 jobs across multiple sectors. The National Alternative Protein Innovation Centre (NAPIC), a cohesive pan-UK centre, will revolutionise the UK's agri-food sector by harnessing our world-leading science base through a co-created AP strategy across the Discovery?Innovation?Commercialisation pipeline to support the transition to a sustainable, high growth, blended protein bioeconomy using a consumer-driven approach, thereby changing the economics for farmers and other stakeholders throughout the supply chain. Built on four interdisciplinary knowledge pillars, PRODUCE, PROCESS, PERFORM and PEOPLE covering the entire value chain of AP, we will enable an efficacious and safe translation of new transformative technologies unlocking the benefits of APs. Partnering with global industry, regulators, investors, academic partners and policymakers, and engaging in an open dialogue with UK citizens, NAPIC will produce a clear roadmap for the development of a National Protein Strategy for the UK. NAPIC will enable us to PRODUCE tasty, nutritious, safe, and affordable AP foods and feedstocks necessary to safeguard present and future generations, while reducing concerns about ultra-processed foods and assisting a just-transition for producers. Our PROCESS Pillar will catalyse bioprocessing at scale, mainstreaming cultivated meat and precision fermentation, and diversify AP sources across the terrestrial and aquatic kingdoms of life, delivering economies of scale. Delivering a just-transition to an AP-rich future, we will ensure AP PERFORM, both pre-consumption, and post-consumption, safeguarding public health. Finally, NAPIC is all about PEOPLE, guiding a consumers' dietary transition, and identifying new business opportunities for farmers, future-proofing the UK's protein supply against reliance on imports. Working with UK industry, the third sector and academia, NAPIC will create a National Knowledge base for AP addressing the unmet scientific, commercial, technical and regulatory needs of the sector, develop new tools and standards for product quality and safety and simplify knowledge transfer by catalysing collaboration. NAPIC will ease access to existing innovation facilities and hubs, accelerating industrial adoption underpinned by informed regulatory pathways. We will develop the future leaders of this rapidly evolving sector with bespoke technical, entrepreneurial, regulatory and policy training, and promote knowledge exchange through our unrivalled international network of partners across multiple continents including Protein Industries Canada and the UK-Irish Co-Centre, SUREFOOD. NAPIC will provide a robust and sustainable platform of open innovation and responsible data exchange that mitigates risks associated with this emerging sector and addresses concerns of consumers and producers. Our vision is to make "alternative proteins mainstream for a sustainable planet" and our ambition is to deliver a world-leading innovation and knowledge centre to put the UK at the forefront of the fights for population health equity and against climate change.