University of Birmingham

UKRI Gateway to Research · FY 2024 · 2024-08

Plants are under constant attack from a diverse set of both old and newly emerging pathogens that cause disease. Diseases of crops take away an estimated 20-40% of our crop yields every year [1], leading to serious food shortages that have devastating impacts on the health and well-being of over 800 million people estimated to be food insecure [2]. To prevent yield losses, we need to understand what tools pathogens use to cause disease; these tools are referred to as "virulence" genes. We also need to understand how pathogens that infect the same crop might share these tools with each other. The sharing of virulence genes between unrelated pathogens is known as "horizontal gene transfer" (HGT). HGT between pathogenic species is dangerous because it can lead to rapid changes in speed at which a pathogen damages the plant, driving much larger yield losses. HGT is also known to lead to the rapid spread of antibiotic resistance genes. While we have a good understanding of the ways in which bacterial pathogens use HGT to exchange virulence/antibiotic resistance genes, our knowledge of how fungal pathogens do this is very limited. This lack of knowledge is of grave concern as fungal diseases are already difficult to control, and the growing negative impact of fungi is a risk to both human and plant health. I have recently discovered that a virulence gene, called ToxA, has jumped via HGT between three fungal wheat pathogens inside of a giant transposon. Transposons, also known as "jumping genes", contain genetic machinery that enables them to move around a genome. The finding of ToxA in a transposon is important because this protein alone can cause serious disease symptoms on wheat, and if transferred to a new fungal species a new disease could emerge. These giant transposons belong to a new transposon group called "Starships". They are unusual because of their large size, often exceeding some small fungal chromosomes, because they carry many genes. I hypothesize that the extra genes that Starships carry enable them to move themselves between different fungal species. The goal of this Fellowship is to uncover how Starships jump both within a genome inside one species and also between different fungal species, with the intention to use this knowledge to then predict which fungal species Starships can hop into. Starships have only been described within the last year making them very novel and exciting new components of fungal biology. I aim to be one of the first groups in the world to understand how these Starships work and how they might threaten our global crop yields by moving dangerous genes between different fungal pathogens. In the long-term my aim is to adapt these transposons for our own use in biotechnology by programming them to capture genetic material of our choice and moving this material into a suitable host for further study. Adapting natural systems, such as Starships, for our own use in bioengineering has led to several monumental steps forward in human health, sustainable production of biomaterials and medicines. [1] https://www.gov.uk/government/statistics/united-kingdom-food-security-report-2021 [2] https://www.fao.org/3/cc0639en/online/cc0639en.html

UKRI Gateway to Research · FY 2024 · 2024-08

The success of modern technology is dependent on the availability of a large number of materials with different properties. Historically, this has led to a reliance on natural materials for delivering a desired function, some of which are scarce or have non-ideal properties. Over the past 20 years, extensive laboratory studies have demonstrated low-dimensional materials as an exciting group of advanced materials that can provide solutions to many of the major challenges society faces, including energy storage and generation, resource sustainability, pollution remediation, and health care. Their extraordinary material properties emerge when one or more of their dimensions comprise of only a few atomic or molecular layers. Two-dimensional materials such as graphene, transition metal dichalcogenides, and MXenes, for example, are atomically thin materials with an enormous range of physicochemical properties. They can be exfoliated from bulk crystals to engineer nanosheets with custom properties that are dependent on their thickness (such as direct band gaps). Despite their advantages and exciting prospects, one major restriction limiting their integration within our technologies is scalable, controllable manufacturing of high quality materials. Current processes produce materials with uncontrolled nanosheet morphologies, leading to materials that are not optimised for end-user applications. This is a universal issue for all high-volume, top-down manufacturing approaches, and leads to an unnecessary use of resources to compensate for the deficiency in material quality. A compounding issue is the poor yield often obtained in manufacturing processes (~1%wt). The most environmentally sustainable exfoliation processes are mechano-chemical, avoiding the use of toxic oxidising agents by producing materials using mechanical force (e.g. shear exfoliation). While this is admirable, up to 99% of the feedstock material does not get converted into a valuable low- dimensional material, and instead this ends up as waste. This introduces environmental problems, mineral under-usage, and resource security concerns for the UK given many raw materials are located in other geographical regions. The aim of this project is to address these issues by creating a self-driven manufacturing solution that produces high quality materials with custom properties on-demand, while simultaneously embedding circular economy principles for reusing the vast quantities of feedstock that end up as waste from these manufacturing systems. Underpinned by interdisciplinary research spanning fluid dynamics, materials science, engineering, and applied data science, a transformative manufacturing solution will be developed that significantly departs from the state-of-the-art. It will be scalable and process-agnostic, manufacturing custom materials from all types of liquid-exfoliation processes (chemical, mechanical, electrochemical) and easily transferrable into a rapidly growing UK industry. This will open up the route for sustainable industrial scale manufacturing and facilitate the large-scale growth of novel technologies and functional devices that will lead to a more sustainable society.

UKRI Gateway to Research · FY 2024 · 2024-08

This project aims to explore novel design methodologies and implementation techniques for high-performance mm-wave and terahertz waveguide devices for space and terrestrial applications in the next generation 5G/6G communications. Microwave filter design has become an establish art. However, as frequency goes higher into millimetre-wave and terahertz regime, filter design faces a whole new set of challenges from improving the insertion loss, to reducing the dimensional sensitivity and therefore increasing the manufacture yield. This not only challenges microwave designer but also the manufacture techniques. To meet the demands of future space and satellite communications for 5G, 6G and beyond, which will feature millimeter-wave and terahertz regions, there is a need for a general and novel design methodology to synthesize and manufacture the waveguide filters and filtering components by exploring new and advanced machining techniques. The goal is to achieve filters with high unloaded quality factor, low insertion loss, high selectivity, low sensitivity, low geometrical complexity, high power handling capacity, and high fabrication tolerance. First, a new and general methodology for synthesizing inline elliptic-function filters using a modular approach based on novel resonator sections will be presented. Then, Novel solutions with new topologies and resonator structures will be proposed and experimentally verified to demonstrate low-loss and desensitization to manufacture tolerance in the modeling and implementation step. Finally, based on the methodology and strategy, fabrication and demonstration of the waveguide components using advanced 3-D printing and micromachining techniques will be completed, by a Design-for-Manufacture (DFM) approach.

UKRI Gateway to Research · FY 2024 · 2024-07

The problem we wish to solve. Whole-genome sequencing of microbes offers new ways of understanding the development, transmission, and prevention of antimicrobial resistance (AMR). It is an exceptionally promising, rapidly developing area, which provides rapid, detailed genomic information on antibiotic-resistant bacteria that can be used for diagnosis and surveillance of AMR in clinical and agricultural settings. While genomics (the field of DNA sequencing technologies and bioinformatics) has revolutionised our understanding of microbes and AMR, it is not currently clear how the rapid developments in genomics can be efficiently translated, at scale, into practical and cost-effective tools that reduce current and future harms associated with AMR. No single discipline can resolve this complex process of translation in isolation. Instead, transdisciplinary working is essential to progress the many possible ways genomics could contribute to countering the threat posed by AMR. These include an exploration of the better use of the UK's unique capabilities in the field of DNA sequencing technology R&D and development, the ethical implementation of Artificial Intelligence (AI) to analyse large genomic datasets, the possibility of developing new diagnostic technologies to guide future prescribing in both human and veterinary medicine, and the possibility of using genomics to shape and change infection prevention and control practices across health and social care. These translational challenges require the input, expertise, and the establishment of a common language and set of goals from many perspectives. To this end, the Transdisciplinary Antimicrobial Resistance Genomics network (TARGet) will bring together researchers in social sciences, the humanities, biomedical and veterinary sciences, and applied health, and product developers, governmental organisations, industry, and the general public to bring genomics from the laboratory to clinical and veterinary medicine, and to leverage genomic information to inform the development of novel diagnostics and infection prevention practices. What the leadership team will do. We will support the growth of a dynamic network of diverse experts and organisations. The transdisciplinary leadership team are well-connected to multiple research communities across the UK and internationally, to industry and to other stakeholders in the NHS, social care and veterinary medicine. The leadership team is thus exceptionally well-placed to recruit a far-reaching network of different stakeholders all of whom will make valuable contributions to future research harnessing the potential of AMR genomics. The TARGet leadership team will be responsible for transdisciplinary network-building activities, including surveys, online and in-person meetings, and selecting transdisciplinary research projects for pump-priming funding. What the network will achieve. TARGet will initially use monthly transdisciplinary, interactive webinars that focus on the range of data-types, skills, knowledge, theories, and methods used across the full range of collaborating disciplines and organisations involved. In this way, the webinars ensure that every discipline's stakeholders learn about the others' perspectives and potential contributions. Activities in the first year will ensure the network develops a deep understanding of the multitudinous assets it has, and will increasingly work synergistically to translate the potential of AMR genomics into real-world actions and impacts. These online events will be complemented by major in-person plenary events. Finally, towards the end of the project, the activities of the network will focus on the documentation of successful implementation of AMR genomics across different sectors, and the co-production of a programme of future research projects and policy recommendations that rely on transdisciplinary working to deliver optimal solutions.

UKRI Gateway to Research · FY 2024 · 2024-07

Proteins are intricate and extensively modified molecules that engage in the formation of loosely-bound complexes with themselves and other biomolecules. Functioning as biological machines, proteins orchestrate the vital processes essential for life, with their roles intricately tied to both their composition and overall structure. Mass spectrometry is an analytical technique which enables us to dive into the workings of proteins, offering a deeper understanding of their functionalities. This proposal will install the most advanced mass spectrometer for structural biology at the University of Birmingham. This state-of-the-art instrument has the capability to unravel the characteristics of newly identified proteins, shedding light on their coordinated movements with partnering molecules. Equipped with a high mass quadrupole, the mass spectrometer boasts the ability to analyse a diverse variety of large proteins and protein complexes in real time. Crucially, this quadrupole enables low-abundant yet critical proteins, whose misregulation can lead to significant alterations in cellular function, to be isolated in-turn and picked out for analysis from within complex mixtures of hundreds of proteins. In addition, the mass spectrometer will be equipped with a variety of fragmentation techniques that will enable each protein to be characterised with certainty, adding a high level of precision for accurate identification and protein function assignment. By uniting a broad range of researchers from the University of Birmingham and the Midlands region (University of Warwick, University of Leicester) whose research interests span diverse disciplines, the proposal will apply this state-of-the-art technology to unlock our capabilities to resolve key challenges within key strategic priorities that have been outlined by the BBSRC; understanding the rules of life, transformative technologies, bioscience for sustainable agriculture and food, and biosciences for an integrated understanding of health.

UKRI Gateway to Research · FY 2024 · 2024-07

Over 800,000 sinus lift procedures are performed annually within a £2.3billion dental and orthopaedic bone graft substitute market. In dental grafting, patients' own bone (autograft) gives the highest success (98.5%, 1-5 year follow up) however, limited availability, increased operative time and patients suffering from blood loss and morbidity means grafts derived from animals (xenograft) are the standard of care. Xenografts also suffer from the lowest success rate (73%) for 1-3 year follow up. In addition, failure in sinus lifts often occurs due to granular xenografts perforating and tearing the sinus membrane (10-20%), leading to severe complications including infection (3%) and significant pain. The sinus bone grafting market is dominated by two large companies; Botiss and Giestlich. Their market occupancecan hinder market entry but there is a clear clinical and patient need for better solutions in sinus lift bone grafting. We have developed a synthetic fibrous material; Biowool™ which is a 2nd generation bioactive glass to be constructed into cotton-wool-like structure. Its 3D form is a unique selling point for sinus lift procedures giving a competitive advantage over other products. Whilst the market leaders, Bio-Oss® and maxresorb® are granular and non-resorbable, Biowool™ is fully resorbed in <8 weeks. Its cotton-wool-like nature makes application easy within a sinus lift procedure, reducing the chances of perforation of the sinus membrane giving significant patient benefit. This MRC DPFS project will enable setting up of a QMS, produce Biowool™ to scale at an ISO 13485 certified facility and to develop protocols for GLP preclinical product safety assessment via CROs. We have provisionally mapped suitable partners and clinical champions for Biowool™ to successfully deliver this project.

UKRI Gateway to Research · FY 2024 · 2024-07

In the realm of data explosion, it is usually the case that a single computational processor is unable to store the vast amount of data needed to do any meaningful computation. The data are generally distributed among a large number of processors/servers who need to communicate with each other via a network in order to perform various computational tasks. The recent trend in big data is a case in point where the rapid acquisition of a vast amount of data makes it impossible for a single processing unit to handle. This problem is generally addressed via different storage architectures for fast access and efficient software paradigms such as MapReduce, Hadoop, and Spark. The general bottleneck of any such system can be abstracted by the following natural computational scenario: Suppose a computational system, consisting of several processors, wants to perform a task where the input is distributed among the processors. Instead of being concerned with the computational time that is required, we are interested in the communication that the processors need to do among themselves in order to perform the task. Apart from big data, this problem, and many of its variants, appear frequently in practice in many guises and in different levels of abstractions--in network protocols where the goal is to minimize the communication (and thereby error in the communication) between two network hubs, in VLSI circuit design where the goal is to minimize energy used and to pack efficiently by decreasing the number of wires required, also in data-structures, circuit complexity, auctions and a plethora of other interesting areas of study. Many sequential algorithms that were widely used in the past have become greatly inefficient in practice for such distributed systems. The main goal of the proposed research is to design (or prove the hardness of) fundamental network algorithms and their generalizations in such distributed models of com- putation. Among them, the model of two-party communication and query protocols highlight different challenges in accessing information for distributively processing data over such large networks where the complete input is not explicitly accessible, hence we exclusively focus on them in this project. Our goal is to study basic graph-algorithmic problems in these models to thoroughly understand how to overcome different communication bottlenecks. We will study them in classical setting (deterministic and randomized/stochastic) as well as in the quantum setting as quantum computing is undoubtedly the model of computation of the future. Because of our reliance on efficient network algorithms in modern day-to-day life, we believe that such research will have a large eventual impact on other areas of computer science and engineering and, at large, society-this is an important ingredient of the UK government's RD roadmap of supporting long-range, fundamental, underpinning science and research. The graph or network problems we plan to study fall into two broad categories: connectivity-related problems and flow-related problems. These two classes of problems have been extremely well studied for over half a century and are arguably the two fundamental classes of network problems with countless applications in other areas of research (e.g., operations research, scheduling, image segmentation, network clustering) and in modern society. Moreover, they have seen surprising progress in recent times. The novelty of our approach towards these well-studied graph problems is the following: We expect, from previous experience, that the insights gained from studying the communication and query complexity of these problems will advance our understanding in diverse research areas such as distributed, sequential and dynamic algorithm design. This project can be viewed as the first step toward systematically studying such universal and cross-paradigm algorithm design techniques.

UKRI Gateway to Research · FY 2024 · 2024-07

All numbers are even or odd. But why? How could I prove this *formally*? One way is to notice that the parity of a number flips every time we add 1, another way is to just check the last digit. Both of these 'proofs' induce an 'algorithm' for checking whether a number is even or odd. However in the latter case the algorithm is exponentially more efficient, - we only need to look at one digit rather than generate the entire number from scratch. In this way we can say that the two proofs are really *different*. 'Structure vs. Invariants in Proofs' (StrIP), at its most abstract level, is concerned with understanding when two proofs are different or the same. This is a question in proof theory that can be traced back to the early 20th century, and is often known as Hilbert's 24th problem. While it is a fundamentally theoretical question, Hilbert's 24th problem and the proof theoretic endeavours that have followed underlie many aspects of modern computer science, such as programming language theory and computability theory. In particular, proof theory is one of the foundational pillars of Formal Verification. This is an emerging field that allows us to often *guarantee* that software functions correctly, and is set to become increasingly relevant for certifying software in the real world. However, there remains one fundamental barrier to resolving Hilbert's 24th problem: inductive reasoning. 'Induction' is a powerful proof technique that is indispensable in mathematics and computer science; it allows us to prove a property P(x) for all numbers x by first proving P(0) then proving that P(x) always implies P(x+1). It is like an infinite sequence of dominoes: if I knock over the first one, every other one will eventually fall. On the computing side, a proof theoretic treatment of induction is a necessity in order to reason about general computer programs. The goal of StrIP is to give a comprehensive treatment of induction via the notion of 'cyclic proofs'. This is a phenomenon that has emerged in computational logic over the last 20-30 years and allows us to decompose induction into finer computational steps in a finitary way. By combining this with other recent ideas in proof theory, so-called 'Deep Inference', StrIP will build a bridge between two of the most important subjects in theoretical computer science: proof theory and automata theory. Ultimately, the goal is to apply the techniques developed to Automated Reasoning via concrete implementations, and more generally to the automated verification of computer programs.

UKRI Gateway to Research · FY 2024 · 2024-07

Nowadays, comfort is a design requirement of all structural products that guarantees the quality and competitiveness. Noise constitutes a significant form of environmental pollution that impacts the lives of hundreds of millions of people globally, leading to various socio-economic consequences. Intense vibration has the potential to jeopardise both the structural integrity and the performance of equipment and hardware, and produce significant level of noise thereby affecting the comfort of individuals in several aspects. Subways represent a primary source of ground-borne noise and vibration in urban areas. Over 7.5 million Europeans face potential disturbance from railway noise and vibrations. In response to public concerns, governments have established laws and regulations to limit the permissible exposure of citizens and facilities to ground-borne noise and vibration. The goal of the META-NOVIB project is to develop a comprehensive framework to effectively predict and control the vibration and noise induced by underground railway tunnels using digital twin technology supported by machine learning tools. This system provides valuable insights for engineering decisions throughout the operation and maintenance of these tunnels. Additionally, it evaluates the performance of seismic metamaterials (SMM) in attenuating the level of noise and vibration to meet the allowable limit. META-NOVIB will provide an integrated platform for visualisation and real-time prediction and virtual control of the railway-induced noise and vibration during the operation and the maintenance phase. Thus, the output will have wide implications on the health of nearby residents due to vibrations and prevent any structural damage to historical buildings or structures, with high academic and industrial impact.

UKRI Gateway to Research · FY 2024 · 2024-06

The mantle is the largest component of the Earth, comprising 84% of our planet's volume. Although the mantle is solid, over geological time it churns vigorously like a fluid in a process known as mantle convection, driven by heating from radioactive decay in Earth's interior and cooling from above. Mantle convection deforms the Earth's entire surface into an interlocking pattern of swells and depressions known as "dynamic topography", with diameters of several thousand km and heights of several km. Dynamic topography influences oceanic current patterns, land surface erosion and accumulation of the eroded sediment, and these effects are known to control the distribution of valuable natural mineral resources. Volcanic activity also usually occurs in association with the hot, rising elements of the convective circulation, known as mantle plumes. The most vigorous mantle plumes give rise to Large Igneous Provinces (LIPs) - episodic huge outpourings of lava accompanied by voluminous release of greenhouse gases to the atmosphere. LIPs coincide in time with some of the most remarkable perturbations to global climate, ecosystems and the carbon cycle in Earth's history, including mass extinctions, Ocean Anoxic Events, and the largest natural global warming event of Cenozoic time. Whilst it is widely accepted that mantle convection has influenced Earth's surface and climate processes over geological time periods (tens of millions of years or more), these time frames are too slow to explain the rapid onset and short duration of the environmental changes that usually coincide with LIPs. But growing evidence now suggests that patterns of mantle convection, dynamic topography and igneous outpouring can evolve in less than a million years. Key to this theory is a process known as "Thermal Plume Pulsing", in which hotter and cooler blobs of mantle are carried along with the convective circulation within a mantle plume. The hottest pulses within the biggest mantle plumes, such as the Icelandic Mantle Plume, can rise at speeds in excess of 200 mm/yr, which is faster than the motion of tectonic plates, and can cause changes in local sea-level of over 1 mm/yr, similar to modern mean global sea-level change. At such speeds, past pulsing of the Icelandic Mantle Plume could have activated greenhouse gas generation from the North Atlantic LIP rapidly enough to explain the Paleocene-Eocene Thermal Maximum extreme global climate change event, the best natural analogue to anthropogenic climate change. However, the Plume Pulsing hypothesis is not universally accepted for Iceland or Earth's other major mantle plumes as key data is lacking. High-quality measurements of seafloor features near Iceland known as the "V-Shaped Ridges" (VSRs) that comprise the world's best record of the suggested hot pulses will address this gap. Working with the lead advocates of the alternative models for VSRs, we have devised an experiment to determine the origin of the VSRs by measuring both the thickness and the chemical composition of the crust that builds the VSRs. A high-quality geochemical survey of the basaltic seafloor was made recently, and it will soon be augmented by an international drilling project. Now, IMPULSE will measure the variation in thickness and seismic velocity (hence bulk composition) of the entire crust beneath several VSRs for the first time. Our pilot work indicates that IMPULSE will provide firm evidence for fluctuations in mantle temperature on a million-year timeframe to give the first definitive proof of the Mantle Plume Pulsing hypothesis. Furthermore, by formally correcting for the complicating effect of mid-ocean ridge tectonic processes on VSR crustal thickness for the first time, our new VSR record will determine the shortest time period for fluctuations in mantle temperature. These results are crucial to test hypotheses for how mantle convection has influenced Earth's surface and climate proceses.

UKRI Gateway to Research · FY 2024 · 2024-06

The project 'Super High Power and Energy Electrode Designs for Metal-ion Batteries' (SPEED) is focused to demonstrate a sustainable 'Hybrid Battery' (HB) technology by combining materials which demonstrate different charge storage mechanisms in a single device, decoupling energy and power. High surface area materials store charge as an electric double layer capacitance (EDLC) and redox- active materials can store charge in the bulk particles, such as in batteries. If suitable green principles are used from concept through to end-of-life and recycling, the materials' life cycle can be optimised. SPEED will highlight the integration of renewable energy generation, emission reduction, e-mobility with improved resource efficiency targeted for the European Union (EU) aim of Net Zero by 2050. This novel concept has enormous potential to overcome the drawbacks of both supercapacitors and batteries such that high power and high energy density can be achieved in a compact system with improved charging rates. Sustainability will be addressed through materials choice, using abundant materials such as Aluminium, Sodium, Magnesium, Iron and Manganese rather than critical materials such as Lithium, Cobalt and Graphite. Multi-material concepts which combine the different surface area materials, and ion transport combinations will be used to maximise performance properties. High-charge aluminium ions will be used for high surface charge storage, whereas sodium ions for bulk charge storage. A lab-based prototype will be developed to underpin the fundamental understanding of hybridised technology for long-term industrial and emerging technologies. Devices fabricated using this composite will provide an enhancement in the frontiers of science & technology associated with the aim of clean energy usage leading to economic prosperity for all.

UKRI Gateway to Research · FY 2024 · 2024-06

This project aims at transforming wide-field microscopy by adding single photon capabilities that are so far only available in confocal microscopy. We will use the latest generation of single photon sensitive imaging sensors with improved photon detection efficiency and embedded data processing circuits to enable the recording of single photons at MHz rate with picosecond accuracy. This will significantly reduce the readout noise and enable different new imaging modes in wide-field microscopy such as fluorescence lifetime imaging and photon correlation imaging which can be used for multiplexing or molecular counting. In this project, we will focus on improving different super-resolution microscopy techniques for imaging fixed and living cells. For instance, the localisation precision in single-molecule localisation microscopy (SMLM) will benefit not only from the reduced noise levels but also from the possibility to distinguish and reject instantly scattered light from the delayed light emission of the fluorescent labels. Moreover, the embedded photon histogramming capabilities will allow to implement fluorescence lifetime-based multiplexing and thereby increase the number of different labels that can be used in a sample. We will also explore the potential for probing molecular interactions in cells using single-molecule Forster Resonance Energy Transfer. Overall, we expect that this will improve the achievable resolution, add inherent quantitative information to the image data and increase the number of proteins that can be simultaneously imaged. We will explore the application of single-photon SMLM by imaging protein complexes of tetraspanins in the plasma membrane of fixed cells. Furthermore, we want to increase the spatial resolution of super-resolution optical fluctuation imaging (SOFI) and enhance its capabilities in live-cell super-resolution microscopy. Here, the high time resolution of the single photon sensitive imaging sensor will allow us to extend the timescale that can be used for correlating the intensity fluctuations in SOFI. This is very relevant because the majority of optical fluctuations occur on the microsecond timescale which is not covered by current imaging sensors such as EMCCD and sCMOS cameras. Thereby, we expect a significant improvement in the achievable resolution and at the same time a better separation of fluorophores with different properties. We also expect to overcome a major limitation in SOFI by increasing the number of fluorescent labels that can be used in SOFI experiments. Like for single-photon SMLM, we will implement time gating and fluorescence lifetime multiplexing to further reduce noise and increase the number of probes that can be simultaneously imaged. We will explore the suitability of single-photon SOFI by imaging visualising the same protein complexes of tetraspanins and their dynamics in the plasma membrane of living cells. Overall, we expect that the single-photon super-resolution microscopy developed in this project will significantly improve the achievable spatial resolution due to a significantly reduced noise level and rejection of immediate scattering. At the same time, single-photon wide-field microscopy will enable additional imaging modes such as fluorescence lifetime imaging microscopy (FLIM) which will increase the number of simultaneously imaged targets, and photon correlation imaging which will enable quantitative molecular imaging as the first quantum imaging technique in wide-field fluorescence microscopy. The successful development of single-photon super-resolution microscopy will be door opener for other imaging modes such as fluorescence correlation imaging of fast molecular processes. In summary, this will lead to a step change in wide-field microscopy with great prospect to transform the way we can image molecular scale structures and processes in the life sciences and in biomedical research.

UKRI Gateway to Research · FY 2024 · 2024-06

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.

UKRI Gateway to Research · FY 2024 · 2024-06

Few problems in fundamental physics are as clearly motivated or as important as discovering the nature of the elusive dark matter that accounts for most of the mass of the universe. Direct detection experiments located deep underground are searching for the rare interactions of these well-motivated, relic particles in very sensitive detectors. Liquid xenon (LXe) technology has led these searches for over a decade. Recently, the top international collaborations in the field have come together in the XLZD consortium to build the definitive experiment: one able to discover or rule out electroweak-scale particle dark matter in the accessible parameter space remaining above the very challenging neutrino background. Exciting opportunities exist also in neutrino physics, including establishing the existence of neutrinoless double-beta decay; this is another paradigm-shifting discovery which may be accessible to such an experiment, which could explain the matter-antimatter asymmetry in the universe. This proposed 'rare event observatory' will deploy a LXe detector with up to 80 tonnes of 'active' mass in an ultra-low-background experiment to address these and other questions, at least two of which could entail Nobel-Prize worthy discoveries. This Pre-Construction project prepares the UK contribution to the XLZD experiment and builds the case to bring this ambitious international experiment to the UK. STFC is developing a major new underground laboratory at the Boulby mine, and XLZD would be the centrepiece of the new state-of-the-art facility. A future construction project must be carefully prepared, and this development work is delivered through this Pre-Construction project. The proposed UK contribution to XLZD includes major experimental hardware systems, especially those most naturally suited to the host nation; these will be designed and prepared in this phase. In addition, we will deliver with key industrial partners bold programmes for clean manufacture underground, for engineering and skills development, and for environmental sustainability. These programmes relate to challenges that must be addressed, but which we deliberately develop into opportunities: to provide return to UK industry and wider economic impact, to develop capabilities that support future STFC and UKRI projects, and to be a pathfinder in how Big Science moves towards Net Zero.

UKRI Gateway to Research · FY 2024 · 2024-06

Plastics are ubiquitous in modern life, with global production of ~260 million tonnes per year and only 9 % recycled in 2019. 8.3 billion tonnes of plastic have been produced in total and predicted 12 billion tonnes in landfill or environment by 2050, taking 400 years to degrade naturally. In future, a strong growth in demand for and production of plastics is expected, whilst concerns for the greenhouse effect necessitate that carbon dioxide emissions and reliance on fossil fuels are decreased to meet legislation. Plastics can be recycled via a range of mechanical, thermal and chemical techniques, each route having advantages and disadvantages. Some chemical recycling techniques, such as glycolysis, are applicable only to particular types of polymer. Other routes, such as mechanical recycling, produce a lower grade product, whilst thermal techniques require a high energy input. Mixed waste, including halogenated polymers such as polyvinyl chloride presents a challenge, as the chlorine is a potential catalyst poison. A recycling and upgrading process is thus required that can process a range of different pyrolysis oils derived from polymers as part of a mixed waste stream, can deal with contaminants and produce a value-added product. In Catawave we aim to address the above issues and develop a robust and energy efficient process to upgrade pyrolysis liquids derived from a range of plastic waste streams. To do this we bring together several novel requisite technologies, which will include the development of bespoke catalysts to effectively upgrade the pyrolysis oils. These will be formulated from industrial metal processing or mining waste by-products such as 'red mud' and known hydrocarbon cracking catalysts such as zeolite ZSM-5, and select samples will incorporate microwave susceptible carbon particles to aid their heating. We will assess whether microwave or induction heating in a flow reactor can deliver a more effective and energy efficient process compared with conventional resistive heating, in conjunction with the developed catalysts. The upgraded oil products will be characterised using a range of techniques, with aim of upgrading to increase the value of products, including upscaling to meet standards required for drop-in fuels. Fresh and spent catalyst will be characterised using a range of techniques to understand their catalytic behaviour and deactivation. The results of the experimental studies will be applied to develop a kinetic model using lumped approach comprising component groups, which would be used to inform the design and scale-up of reactors for an industrialised process. Techno-economic modelling will be developed to inform the process scalability and profitability, for example the selection of tonnage throughput, distributed or centralised processing of waste. We have engaged Project Partners from across the waste producing, recycling, fuels and process simulation sectors including Sabien Technology Plc, Halocycle, Severn Trent Green Power, Pressvess and Mitsubishi Chemical. They will provide samples of pyrolysis oil for upgrading, advise on catalyst formulations, assist with process design and economic evaluation, give technical consultation on the work plan and help setup routes to commercialisation and impact delivery as outlined in their letters of support.