University of Bath

UKRI Gateway to Research · FY 2025 · 2025-06

Every year chronic diseases, including neurodegenerative and cardiac diseases, cause 40 million deaths worldwide. This toll is predicted to double in the next twenty years, based on an ageing population, population growth and unhealthy lifestyles. In the UK, chronic conditions are the leading cause of deaths and disability, affecting approximately one in three of adults. GLUTRONICS seeks to enhance the quality of life of the millions worldwide affected by chronic conditions, and reduce the incidence of the associated premature deaths, by advancing the progress on implantable bioelectronics for personalised therapy though long-lasting, lightweight and miniature implantable power sources. The use of bioelectronics in healthcare is fast-growing; the UK government has recognised as critical the development of innovative technologies, such as neuromodulators and electroceuticals, that can support preventative, personalised and digitalised care by enabling real-time monitoring, informing on disease progression, and providing tailored intervention. Nonetheless, current implantable medical devices are invasive, primarily due to the need for a power source, typically lithium-ion batteries, which can represent over 80% of the total volume and weight of a device. Lithium batteries hinder long-term use and comfortable deployment of medical devices because are difficult to miniaturise and require high-risk routine surgeries for replacement. As an example, the neurostimulation of the cervical vagus nerve for the treatment of patients affected by epilepsy, requires the implantation of the bulky pacemaker battery in the chest (approximately the size of a tea bag of 20-50 gr), which is connected to electrodes located in the neck via extension wires. In the UK, there are approximately 60,000 children who suffer from epilepsy and may need to have such an invasive device implanted in their body. Moreover, although the neuromodulation of the vagus nerve has shown potential therapeutic benefits for several conditions, including depression, attention disorder and Parkinson's, the invasiveness of current bioelectronic devices, and the consequent major intervention their installation would require, makes their use for these conditions unpractical. GLUTRONICS will lead to a new generation of bioelectronics that are powered by the sugars naturally present in physiological fluids with cutting-edge glucose fuel cells. With a team's experience spanning research on fundamental science (electrocatalysis, glucose fuel cells, mathematical modelling), proof-of-concept trials in animals, in-human studies, regulatory approvals, and commercial translation, and with a cohort of industrial collaborators, GLUTRONICS will globally lead innovation on implantable glucose fuel cells. This success will be possible by: i) generating stable and biocompatible, fully-integrated abiotic glucose fuel cell designs, optimised for maximum power extraction; ii) creating a safe implantation design and an artificial subcutaneous pocket that enables long-term operations thanks to a continuous replenishment of glucose and minimum biofouling risks; iii) creating an implantable monitoring system to measure daily rhythms for tailored in vivo energy management. Load cell tests, both in vitro and in vivo, will simulate the powering of a neuromodulator (power demand >1µW). Chronic tests in large animal models (i.e., pigs), in surgical sites that align with potential areas of application, will demonstrate the clinical potential of the proposed technology. Technical, legal and ethical challenges in the research will be considered via dedicated co-creation activities and several other engagement initiatives, which will provide inputs from a diverse range of stakeholders (patients, carers, clinicians, Med Tech experts, health economists, policymakers) and enable responsible innovation.

UKRI Gateway to Research · FY 2025 · 2025-06

Chiral nanoparticles (NPs) can serve as components of vaccines and antibacterial agents, drug formulations against cancer and neurodegeneration. However, the methods for discovery and safety assessment of NPs as drugs are growing inadequate. Here, we aim to drastically accelerate discovery of NP-based medicines taking advantage of their chirality and of novel nonlinear optical effects that are compatible with data-rich high-throughput chemistry processes. Chirality (i.e. mirror asymmetry) is in most building blocks of life –DNA, proteins, etc. Mimicking proteins, chiral inorganic NPs can strongly interact with biomacromolecules forming sophisticated biological complexes with nanoscale dimensions and high biological activity; e.g. triggering an enhanced immune response [NAK, Nature2022, 601, 366] or killing viruses [NAK, Nat. Catalysis 2022, 5, 694]. The parameter space for such complex NPs is vast and its exploration requires novel high-throughput methods. Current drug discovery protocols rely on libraries of drug candidates but they do not exist for. Instead, we will take advantage of (a) versatile and rapid in-situ synthesis of chiral NPs with amino acids from the US team and (b) breakthrough observations of the UK team who reported the first experimental observation of NPs’ strong chiroptical nonlinearities [VKV, Phys Rev. X 2019, 9, 011024]; these will enable detection of Protein complexes in tiny microliter wells of microplates. NAK and VKV demonstrated a new form of this effect that has a maximum of emission in forward direction, which makes it most suitable for the microplates [NAK & VKV, Nat. Photonics 2022, 16, 126]. Our aims:1) Establish the broad applicability of our methodology to chiral NPs. We will synthesize biocompatible chiral NPs from metals, ceramics, and nanocarbons with broad optical properties (plasmonic, excitonic, dielectric). We will then reveal their nonlinear chiroptical properties. 2) Realize the new chiroptical effects in microwell optical systems. We will build dedicated optical rigs for high-throughput optical systems with robotic microwell positioning. The 2nd and 3rd harmonic scattering from NPs will be measured, revealing a previously unknown chiroptical spectroscopy in data-rich format, informing us about multispectral nonlinearities that are specific to NP interactions with biomolecules. 3) NP binding with proteins: The NPs will be tested with model proteins from bacterial biofilms, viral capsids, and immune cell membranes. The data obtained will be cross-checked in parallel tests with nuclear magnetic resonance, mass spectrometry, etc. providing independent data on formation of NP-protein complexes. The binding sites and constants will be also evaluated computationally using our recently developed models (NAK, 2022 Nature Computational Sci). 4) Apply our new technology, based on Renishaw’s inVia platform: With Renishaw’s active assistance, we will modify our inVia Raman microscope for operation with ultrafast lasers, add polarisation control and a highly sensitive detector, and use the high-throughput microplate scanning hardware and software developed by Renishaw.

UKRI Gateway to Research · FY 2025 · 2025-03

Quantum technologies are expected to revolutionise the future with transformative advancements in the way we communicate, perform computing, design, and diagnose health conditions. The last decade has seen many proofs of principle and early-stage applications using well characterised systems and physical processes. However, the full unlocking of the transformative quantum phenomena for real world application requires platforms which are robust and easily implementable with current manufacturing processes in electronics, sensors and healthcare devices. Historically, solid-state material systems have been the protagonists of the revolution in electronics which has dominated the second half of the last century, a prominent example being the shift from vacuum tubes to silicon field effect transistors. Similarly, quantum is expected to rely, for some of its key application, on solid-state material platforms. Two-dimensional (2D) materials offer unique structural and mechanical characteristics for acting as elements, being easily implementable in the current planar thin film technologies and offering a plethora of electrical, magnetic and optical properties. This is enabled by their common structural motif with covalent 2D crystals bonded by weak van der Waals interplanar interactions and chemical tuneability. While the interest in these spurred from the isolation of graphene years ago, it is only very recently that their potential for quantum applications has emerged and promises a rich playground for new transformative discoveries in quantum. Localised point defects in a 2D material have some unique advantages as platforms for solid state quantum technologies: 1) they offer localized and accessible electronic/optical and spin states with the required coherence characteristics to exploit quantum processes for sensing and 2) they are hosted in a 2D systems which can be easily implemented in photonics/electronics where the qubits can be addressed, written/read, and manipulated. In addition, the atomically thin nature of these materials offers the possibility to further protect the states or use them as truly nanoscale sensors via proximity effects. This project aims at synthesizing, demonstrating and discovering new 2D material platforms capable of effectively using optically active spin qubits in quantum sensing applications. It relies on some recent breakthroughs such as the demonstration of coherent manipulation of optically active spin states in boron nitride (hBN), the engineering of defects in transition metal dichalcogenides, and the unique electronic structure of transition metal dichalcogenides to propose new architectures for quantum sensing at the nanoscale. While other materials have been demonstrated in the past, very successful examples are diamond and Silicon Carbide, in some cases they have shown limitations. The proposed 2D systems here offer a new avenue. The objectives can be summarised in: 1) implementation of recently discovered defects in hBN and their study by optically detected magnetic resonance and coherent manipulation of spin, 2) exploration of new defects in transition metal dichalcogenide for quantum information/sensing applications, 3) magnetic field sensing and imaging of new phases in quantum materials. Future applications of this research are in nanoscale sensors and detectors, with implications for in-vitro biomedical diagnostics, magnetic resonance imaging and photonic quantum chip processors. The generated output will contribute to the UK quantum strategy mission, by offering new solid-state materials for healthcare, ultraprecise magnetic detection and computing power. The research is well aligned with the Canadian government effort in quantum technologies by offering core hardware for secure communication networks and development of new quantum sensing platforms.

UKRI Gateway to Research · FY 2025 · 2025-03

Fungal pathogens within the Candida genus, including C. albicans, C. parapsilosis and C. auris, represent a growing public health concern on a global scale. Resistance to key antifungal drugs, particularly azoles and echinocandins, is on the rise.  Increased virulence or resistance is driven by multiple factors including the dual use of antifungals, but our understanding of these drivers is incomplete. The implementation and utility of genomics in Candida epidemiology significantly lags behind its use for bacterial pathogens, and there is little data on the transmission dynamics of these species between clinical and non-clinical (One Health) environments. Moreover, we lack a detailed understanding of how competitive interactions with co-colonising bacterial species impact the survival and spread of pathogenic fungi. This proposal synergises expertise in genomic epidemiology, bioinformatics and microbiome ecology. We will combine existing genomic data with novel genome and metagenome data from clinical and non-clinical settings from Europe and Australia. We will also characterise extensive wastewater and environmental samples from the UK and NL. We will examine hospital transmission dynamics, and link this with the identification of commensal bacteria that are inhibitory to high-risk Candida strains. This data will inform novel intervention strategies to mitigate Candida transmission.

UKRI Gateway to Research · FY 2025 · 2025-03

Project PINN-PORT aims to develop an automated GIS framework and two application software for assessing tsunami hazards and their impact on industrial infrastructures in ports. The model will be applied to three ports in Cilegon, northwest Java, Indonesia, which are within 200 km of the identified seismic gap region of the Sunda megathrust. This region is estimated to be capable of generating Mw 8.9 tsunamigenic earthquakes in the future. These locations are of particular interest due to Indonesia's vulnerability to tsunamis, evidenced by the significant loss of life in tsunamis like those in Palu and Anak Krakatau in 2018, which resulted in over 5,000 fatalities. Tsunamis have the potential to inflict damage on structures within port areas, in turn, causing operational disruptions with cascading effects on maritime trade. Hence, understanding the tsunami impact on port structures and moored ships is essential. The objectives of this project are to 1: Make ports more resilient and safer to tsunamis by developing innovative hazard analysis tools and harnessing the latest modelling technique namely Physics-Informed Neural Network modelling. 2: Automate the process of tsunami risk analysis to ports with the aid of a GIS-based tool and standalone applications that are user-friendly, even for non-experts. 3: Communicate, collaborate and co-create the resilience tools by consulting with port authorities. PINN-PORT employs a hybrid research approach, combining numerical simulations, analytical studies, and field surveys. Field surveys assess the exposure and vulnerability of structures, and fragility functions estimate the probability of structural damage. The developed tools automate this workflow, making them accessible to researchers and potentially port authorities worldwide. By creating these applications, our aim is to advance tsunami modelling research by improving technological accessibility and simplifying the process.

UKRI Gateway to Research · FY 2025 · 2025-02

At the turn of the 20th century it was difficult to draw a clear distinction between mathematicians and physicists, since many of the greatest scientists worked on every important problem in these fields. One of the most influential polymaths of the era was Emmy Noether, who developed all of the foundational theories which inspired this research project. Her greatest contribution to physics was probably Noether's first theorem, which says that if you want to understand the conservation laws of the universe then it suffices to understand the symmetries of the universe. Conservation laws are the most fundamental laws of physics, giving us clues about the nature of matter, and the shape of space, and so Noether's theorem started a wave of discovery which has been growing and growing for over a hundred years, as mathematicians and physicist seek to understand the symmetries of the universe. Today mathematicians and physicists are much easier to distinguish, however the subjects are still deeply intertwined. In modern day mathematical language, the study of symmetries is called representation theory and the goal of this project is to understand how Noether's algebraic structures can be expressed as symmetries. To rephrase this, my objective is to understand the representations of certain important families of algebras. In ancient Greece a powerful idea was born: all matter can be built up from indivisible pieces - the word "atom" literally means "indivisible" - and in the language of modern particle physics it is well-understood that all matter in the universe can be built up from the fundamental particles. In precisely the same way, the representations I seek to understand are also built from fundamental building blocks, known as irreducible representations. Can we describe these irreducible representations explicitly? Can we determine their structure and calculate their dimensions? In this research project I will answer these fundamental, elusive questions in some challenging but historically important examples. Some of the most important unanswered questions in this field pertain to algebras which we call "modular": this is because the underlying number system is not linear, like the real number line, but is circular like the numbers on the face of a clock. Questions in modular representation theory tend to be significantly harder due to the added complexity of the geometry and the arithmetic. By working with tools on the interface between abstract algebra and geometry this project will make substantial exciting progress in some of the most challenging problems in modular representation theory, showing that Noether's wave of discovery is still growing on the ocean of mathematics.

UKRI Gateway to Research · FY 2025 · 2025-02

"Young people who leave school without good literacy skills are held back at every stage of life" (Education Endowment Foundation (EEF), 2019:2). The EEF adds that Literacy skills are essential for achievement and successful outcomes for all learners, and the Government emphasise that 'it is particularly important to induct pupils into the language which defines each subject' (Department for Education (DfE), 2014:11). The language of a subject, i.e., 'disciplinary literacy' is defined as "learning how to read, think about, write, communicate, and use information like each discipline's experts" (Zygouris-Coe, 2012: 36). Not having command of disciplinary literacy is an entrenched problem leading to under-achievement of learners from low socio-economic and English as an Additional Language (EAL) learners (Hall & Wicaksono, 2020). The COVID-19 pandemic has significantly exacerbated the educational attainment gap among disadvantaged children, it is a "slow motion catastrophe... [that] will continue to have far-reaching consequences for an entire generation" (The Public Accounts Committee, 2023). Language is central to education, and academic language is often challenging for learners regardless of their cultural and linguistic backgrounds. In teaching and learning language serves as the primary tool for accessing, communicating, and evaluating knowledge. Success in English-language high-stake external exams (GCSE, iGCSE, A Level and IB, henceforth exam) is predominantly based on written responses and the outcome is crucial for higher education and future careers. It's argued that 'by attending to the literacy demands of their subjects, teachers increase their students' chance of success in their subjects' (EEF, 2019:2). Literacy is key for all learners in the UK and the growing number of learners studying through English as the Medium Education (EME) at international schools around the world. However, no research is available that systematically characterises disciplinary literacy patterns in students' writing during secondary school exam years (iGCSE/GCSE/A Level/IB) or describes the development of disciplinary writing during the transition from iGCSE/GCSE to A Level/IB. This study will create a corpus of student writing and will analyse literacy and writing development during the secondary school exam years. The study will reveal language patterns that characterise student writing across various educational stages and disciplines. Our comprehensive investigation of language development during the exam years adopts a trinocular perspective, examining language from (Halliday 1996, Matthiessen 2020): Above - the types of texts that students have to write, considering genres as a 'staged goal-oriented purposeful activity that people engage in as members of their culture' (Martin, 1984:25). Around - how disciplinary texts are organised and the relationship between different sections of a text. Below the lexico-grammatical features found in these texts. To achieve this, we draw on the power of corpus linguistics and discourse analysis to provide an empirically grounded rationale for language development and the role of language in construing and representing disciplinary knowledge. Our findings will offer unique insights into disciplinary language usage and development, with the potential for significant educational and scientific impact by: Establishing the inaugural corpus and empirical study of language development across the exam years. 2. Uncovering the grammatical and disciplinary literacy patterns in student writing during this period. 3. Creating a publicly accessible online resource based on authentic student writing, enabling users to explore disciplinary literacy, language development, and various teaching and learning aspects. 4. Informing and supporting national and international research, curriculum policies, and teacher education.

UKRI Gateway to Research · FY 2025 · 2025-02

Context Bath, a double inscribed UNESCO World Heritage city, is home to over 5,000 listed buildings and extensive conservation areas. This makes it an ideal location to address the unique challenges of retrofitting heritage buildings. Across the UK, around 6 million homes are of traditional construction (pre-1919), often featuring solid wall construction and natural, breathable materials. Reducing the energy demand of buildings through retrofit has been identified as key way to meet our climate goals. The Challenge The project addresses the challenge of retrofitting heritage buildings in Bath, which face unique difficulties due to their age, construction methods, and conservation status. These homes typically suffer from poor thermal performance, unhealthy living conditions, and increased risks from climate events.  Existing retrofit approaches often use inappropriate modern techniques, leading to structural deterioration. National schemes also lack provisions for non-mainstream design approaches, and many properties are in Conservation Areas or listed, limiting alterations. Inappropriate modern retrofit techniques can cause structural damage. National schemes do not adequately cater to these non-mainstream buildings. Aims and Objectives The project aims to enable Bath residents to co-design retrofit solutions through civic participation, creating a pop-up participatory space known as an “urban room.” This space will facilitate collaboration between academia, residents, policymakers, and design professionals. The specific objectives are: Co-create a vision for Bath’s retrofit future, providing policy recommendations and engaging stakeholders and residents. Enable retrofit design knowledge exchange between practice, academia, residents, and policy makers. Co-design effective, low-cost technical interventions to improve Bath homes and accelerate energy retrofit uptake. Develop the urban room methodology to engage marginalised voices in dialogue on the built environment. Potential Applications and Benefits The outcomes of this project will directly impact residents by piloting the continuation of an urban room to support low-cost retrofit interventions in Bath. It will inform policy decisions around conservation and retrofit, engaging local policymakers. The community-led data collection approach will inform national retrofit strategies and highlight how academia-public partnerships can address real-world design challenges. Nationally, the research will serve as a replicable model for heritage retrofit. Internationally, it will develop the “urban room” methodology, engaging diverse and marginalised voices and making it transferable to other communities for socially led retrofit responses. This project aims to create a positive vision of Bath’s retrofit future, translating technical knowledge into local know-how and accelerating the uptake of energy improvements to homes. By involving residents in the co-design process, the project seeks to ensure that retrofit solutions are both effective and sensitive to the unique heritage of Bath.

UKRI Gateway to Research · FY 2025 · 2025-01

Individuals who have been exposed to trauma in childhood are at increased risk of poor physical health in later life, particularly including heart problems, high blood pressure and type 2 diabetes. Together these problems are known as 'cardiometabolic diseases'. The development of cardiometabolic disease is strongly related to lifestyle, with certain 'health risk behaviours' being important - for example, smoking, poor diet, poor sleep and lack of exercise. However, how and why childhood trauma leads to health risk behaviours and cardiometabolic disease is not well understood. We propose to complete an in-depth analysis of the potential role of mental health problems in linking childhood trauma to cardiometabolic disease. Childhood trauma exposure has been found to contribute to risk for multiple different mental health problems and is one of the most significant risk factors for poor mental health that has been identified to date, accounting for nearly half of all childhood-onset and a quarter of all adult-onset mental disorders. We also know that some risky behaviours (e.g., problematic drug or alcohol use) are much more common in people who have mental health problems. We want to learn more about whether poor mental health is a factor that links childhood trauma to cardiometabolic disease risk. We will carry out our research in Brazil, building on a study that already exists there. It is important to carry out research in countries like Brazil as most research on childhood trauma focuses on wealthier countries like the UK and the USA, where trauma exposure is less common and tends to be less severe. Cardiometabolic disease is also a major problem in Brazil and other middle and low income countries. The Pelotas 2004 Birth Cohort Study has been tracking more than 4000 individuals since birth, with trauma exposure, mental and physical health, and health risk behaviours each being measured repeatedly since childhood. Participants in this study are now approaching 21 years of age and we will be able to use the data that have already been collected to examine whether trauma exposure leads to poor mental health, and whether this in turn increases risk for cardiometabolic disease. Because participants are still only young adults, very few will have clear signs of cardiometabolic disease, so we will be focusing on the health risk behaviours that lead to those problems (e.g., smoking or physical inactivity). In addition to examining whether and how childhood trauma, mental health and health risk behaviours are associated with each other across childhood and adolescence, we will be carrying out in-depth interviews with a small group of study participants who have experienced these problems, in order to learn about their personal perspectives on why and how they have been affected. Because our research will help us to understand when and how childhood trauma leads to risk of cardiometabolic disease, it will also tell us what we might do to prevent this outcome and when might be a good time to do it. As mental health problems and health risk behaviours are each possible to change, we may ultimately find new ways to break the link between childhood trauma and poor physical health.

UKRI Gateway to Research · FY 2025 · 2025-01

With this funding we will enhance critical, cross-disciplinary capability in surface metrology and spectroscopy at the University of Bath. Specifically, we are looking to invest in two multi-user instruments: New 5-axis 3D optical profilometer Refurbishment of existing 400 MHz NMR spectrometer The optical profilometer has transformative potential to advance material design, characterisation and manufacturing. The state-of-the-art (5-axis 3D) profilometer will measure 3D surface features such as a sample’s surface roughness, topography, flatness, curvature, pitch, step heights, and lateral displacement, creating detailed measurements and 3D images of the sculpted engineering surfaces with extremely high (sub-micron-level) precision. The proposed system is capable of scanning and characterising microscale features on large samples, and the 5-axis functionality with high depth ratio further expands the standard applicability of the technique. It will enable characterisation of sculpted surfaces with high aspect ratios and edges, and those with reflective surfaces, generating unparalleled 3D data for further analysis, and filling the gap between traditional optical microscopy, atomic force microscopy and scanning electron microscopy. We will also use the optical profilometer to perform ‘before and after’ comparative analysis to show areas of wear, micro fractures, fatigue areas and surface integrity analysis after an activity cycle. The device has ‘ready to go’ project applications covering precision manufacturing and engineered surfaces, micromechanical systems, thin film devices, micro-fluidics channels, aerospace and mechanical engineering components, electrical components and biomedical devices. Upgrade of the outdated 400 MHz NMR spectrometer will provide access to the newest analytical methods, and dramatically improve throughput for this ‘workhorse’ liquid-state NMR. NMR characterisation is typically the first step in chemical characterisation, giving a rapid overview of chemical composition and larger structural forms within a liquid sample. This molecular structure analysis is achieved by observing and measuring the interaction of nuclear spins with radio waves in a powerful magnetic field. Bath has a range of NMRs, constantly in use by researchers spanning the chemical and life science domains. The upgraded NMR will allow for state-of-the-art high resolution open access use and include a new probe, acquisition PC and latest software. It is crucial to research progress and delivery that our researchers have access to the latest technological developments and characterisation techniques. These two investments will benefit a very wide range of Bath researchers and students, ensuring their familiarity with cutting-edge technology and methods, and enabling these to be transferred and used when working in industry. Bath hosts 13 large PhD training programmes, many of which will use these two instruments. Two specific examples include: the EPSRC Centre for Doctoral Training (CDT) in Sustainable Chemical Technologies: A Systems Approach, awarded in late 2023, which will train over 60 PhD level scientists and engineers to become tomorrow’s leaders equipped to deliver UK and global needs for achieving sustainable development, and the NERC funded RED-ALERT CDT which will have 47 PhD projects starting over the next 4 years, developing digital aquatic environmental health real-time monitoring systems. The vast majority of these students will use one or more of these new instruments, and thus benefit directly, as well as provide a conduit to broader societal benefit as they take their knowledge and skills further in their careers.

UKRI Gateway to Research · FY 2025 · 2025-01

The proposed research addresses the interplay of trust and governance and the effect on the economic development of South African townships post-apartheid. It examines the potential for self-sustaining growth within these historically marginalised communities, which still face significant socioeconomic challenges. Despite significant political and social transformation since 1994, Townships continue to grapple with high unemployment, inadequate housing, limited access to quality education, healthcare, and other economic opportunities. Township economies continue to depend on linkages to wealthier and more affluent urban areas. Service delivery protests are common, and poverty is increasing. This study proposes that the continued economic disparities coupled with a history of discrimination have created a complex interplay of mistrust in economic governance institutions, identity politics and a sense of hopelessness. The goal is to understand and leverage the unique cultural and economic characteristics of townships to promote inclusive growth and reduce dependency on external economic structures. We cover four themes outlined below: the economic potential, technology as an enabler, finance as an enabler and the interplay of social identities and economic activity. We have selected Mdantsane Township in the Eastern Cape Province and Khayelitsha Township in the Western Cape Province, which present significant contrasts in both demographics and economic conditions. We frame the empirical approach from the view that economic practices and relationships are constituted within the dual spheres of markets and community underpinned by general and particularised trust. We propose to use the Qualitative Impact Assessment Protocol (QUIP) and Participatory Assessment of Development (PADev) to facilitate narrative explanations of the drivers of change in various factors that affect the township economy. The approaches allow us to work backwards from perceived changes in selected domains of respondents' lives and livelihoods and trace the influence of trust and governance in economic outcomes.

UKRI Gateway to Research · FY 2025 · 2025-01

Each cancer patient has a unique combination of proteins that promotes the growth of their tumour. In stratified medicine, these proteins are identified, and a drug that inhibits their function is administered to the patient. This personalised approach is often highly effective and results in less side effects compared to standard chemotherapy. Unfortunately, this approach only works for 10% of patients because inhibitors for most cancer proteins are lacking. Many of these proteins are deemed ‘undruggable’ as they function through protein-protein interactions (PPIs), which are difficult to disrupt with small molecules as interfaces are typically void of binding pockets. However, undruggable proteins possess reactive nucleophilic, or ‘ligandable’, hotspots that can be targeted with molecules called electrophiles. Electrophiles permanently inhibit the function of an undruggable protein by forming a covalent bond at a ligandable hotspot. Identifying a covalent inhibitor that selectively targets an undruggable cancer protein while leaving proteins present in our healthy tissues unmodified is a difficult process. If a drug lacks selectivity it can cause side effects for patients. In this proposal, we will develop a phage display technology platform to enable billions of covalent peptide inhibitors (also known as targeted covalent macrocycles (TCMs)) to be rapidly generated and screened against undruggable protein targets. These molecules combine the properties of a peptide and an irreversible inhibitor, binding to shallow PPI interfaces with high affinity and selectivity by forming interactions over a large surface area and achieving permanent target engagement by covalent modification of a proximate ligandable hotspot. Crucially, we will incorporate a range of tyrosine-targeting electrophiles into our libraries as tyrosine residues are highly enriched at PPI interfaces. To prototype our platform, we will identify a covalent peptide that modifies tyrosine 82 on Ras-like protein (RAL) and blocks interaction with guanine exchange factors (GEFs). RAL-GEF PPIs promote pancreatic cancer progression through multiple mechanisms but are considered undruggable as they lack binding pockets for small molecule engagement. Consequently, a RAL-selective drug could be highly beneficial to a patient population that suffers from limited treatment options. Ultimately, this work will enable selective inhibitors to be rapidly identified for a variety of undruggable proteins, which in the long term will allow more cancer patients to benefit from personalised treatments.

UKRI Gateway to Research · FY 2024 · 2024-12

UK is a leader and one of the pioneers in additive manufacturing (AM) and approximately, 5% of the world's AM industry is based in the UK. The UK's AM industry is valued at £460 million in 2023 and is expected to grow to £809 million in 2028. Globally, the AM market was valued to be over £7.15 billion in 2021 with a forecasted value of £16.5 billion by 2026. To ensure UK's leadership in AM, adventurous innovations such as METALS are necessary to guarantee the competitive advantage of the UK's AM industry. METALS investigates, designs and tests a new additive manufacturing process with high deposition rate for die-less forging of large metal components used in aerospace, space and marine industries. The aim is to eliminate the need for rigid, costly and time consuming production of forging dies. This significantly reduced the time to market from a few years to a few weeks. The flexibility of the process enables updating and changing designs for large structural parts within a few days prior to manufacturing whilst maintaining the production rate and quality. The majority of existing AM processes are slow and rely on melting of the material and fusion of successive layers. This results in excessive heat input and unfavourable material structure. Extensive heat treatment processes are required to improve the material structure and the parts' mechanical properties. These in turn will reduce the production rate in manufacturing systems and increase the energy footprint of the manufacturing process. Controlled heat input and high deposition rates offered by METALS will ensure high productivity and optimal material structure.

UKRI Gateway to Research · FY 2024 · 2024-12

Excess weight increases the risk of several diseases including cardiovascular disease, type 2 diabetes, kidney disease and various cancers. There is a need for preventative strategies for obesity-associated disease, especially for people in the overweight and moderately obese ranges where pharmacological intervention may not be suitable. Low-carbohydrate (ketogenic) diets are popular for weight control. Ketogenic diets increase circulating ketones, which can have favourable effects on cardiometabolic health markers. However, the ketogenic diet has a nutrient composition associated with harms (high-saturated fat/red meat, and low-fibre). The net effects of ketogenic diets on long-term health are unclear. Ketone supplements can increase circulating ketones and could provide benefits of ketosis without needing to adhere to a potentially harmful diet. Establishing causality between complex exposures (e.g., diet) and long-term outcomes (e.g., disease), is challenging. The MRC & NIHR Review of Nutrition and Human Health Research (2017) highlighted an "overreliance (as opposed to reasonable reliance) on observational studies" as a key barrier to progression in the field of nutrition and health. Randomised controlled trials (RCTs) facilitate causal inference, but for long-term outcomes are expensive, time-consuming, and often suffer from waning adherence. Mendelian randomization (MR) can estimate causal effects subject to key assumptions. A challenge to these assumptions includes complex behavioural exposures (e.g., diet), which could be intercorrelated with causal factors. Our proposal will address these limitations with a novel combination of study designs to establish causal effects of ketosis (via diet and supplementation) on obesity-associated disease risk in humans. We will combine a tightly controlled, short-term RCT, with MR to link short-term responses to long-term endpoints. We will examine the circulating (blood) and tissue-specific (adipose and muscle) transcriptomic and proteomic responses to our dietary interventions and translate these to MR by identifying single-nucleotide polymorphisms from genome wide association studies. This approach overcomes limitations of RCTs and MR, as adherence to diets will be confirmed with controlled feeding, and intermediate molecular traits as exposure for MR are less likely to be intercorrelated with causal traits. We will validate our approach with interventions known to alter hard endpoints (e.g., very-low calorie diets). This combined strategy aligns with opportunities highlighted by the MRC NIHR review of Nutrition and Human Health Research (2017), e.g., "Linking biological data to both exposure and phenotype will improve clinical applicability and translation to improve health outcomes" and "prevention-related mechanistic nutritional physiology".

UKRI Gateway to Research · FY 2024 · 2024-12

We know that many signals and functions in the body follow a set pattern that repeats everyday (called circadian rhythms). We also know that the timing of this pattern can have an effect on how well our bodies work - for example, shift workers who are active and eat at night when most people are asleep tend to have more health problems such as diabetes and heart disease. Research using mice shows that these repeating patterns depend on the timing of daily events, like sleep, eating and activity. It is important to study humans as well because mice differ from us both in their behaviour and their metabolism - for example, mice are naturally most active at night and at times when food is limited they become even more active, with the chemistry in mouse muscle responding differently to human muscle. Muscles are some of the most important body parts for metabolism and health as they use most of the sugar and fat that we eat and have the capacity to dramatically increase our metabolism by moving around (contracting) - and an active lifestyle help us stay healthy. To prepare for this project, we did a pilot study where we took small pieces of muscle from the thighs of human volunteers every few hours for an entire day and night. We discovered repeating patterns in human muscle, with genetic signals linked to sugar, fat and protein metabolism going up and down every 24 hours. We did this once with people eating in the normal way during the daytime and fasting while asleep at night but also did other studies where we fed people through a tube during sleep - by feeding continuously we removed the acute responses to mealtimes and so could see the underlying rhythms in metabolism, and how they were affected by nutrient availability. Now that we have seen these patterns in genetic signals, our proven method of collecting human muscle samples for 24 hours whilst feeding continuously (even at night) can be used to study whether those signals actually change how our muscles use carbohydrate and protein over time. We will also be able to find out whether these rhythms in metabolism depend of whether and when the muscle contracts (by asking people to move around at different times of day). To study cause and effect we will use an experiment where volunteers are randomly divided into three groups: one group will rest for 24 hours, one group will be more active in the morning and the final group will be more active in the evening. We will then be able to see the pattern of metabolism in human muscle for the first time and can compare the muscle samples between the groups to learn about how rhythms in chemical processes are affected by muscle contraction. As an extra follow-up question, the volunteers will also then continue with their prescribed pattern of rest and activity for two weeks as part of their normal lives, just so we can explore how their muscles and health change in that time. Our prediction is that there will be clear 24-h rhythms in muscle metabolism, with more carbohydrate and protein taken into muscle to be used or stored earlier in the day. We also think that muscle contractions in the morning will be especially important in driving these rhythmic differences in metabolism over the course of a day. This research will provide the first information about changes in how our muscles use carbohydrate and protein over time and in relation to our activity patterns. This will improve understanding of how and why daily patterns as sleep, activity, diet and medications can be used to improve human health.

UKRI Gateway to Research · FY 2024 · 2024-11

As global economies face the challenges of ageing  populations, climate change and increasing inequality, the production and implementation of models capturing the full complexity of these interwoven phenomena is of paramount importance. This early stage project will apply stochastic optimal control and cutting edge, neural network (NN) based, numerical methods to produce a novel framework for analysis and computational resolution of complex, micro-founded, macroeconomic models. The proposed framework will allow for the treatment of dynamic models, incorporating multiple, interlocking, features, allowing for more accurate validation of economic theories and in the long term, policy evaluation.   Micro-founded, macroeconomic models derive, large scale, emergent economic processes, such as employment rates, wealth distributions and savings rates, from assumptions on the preferences and optimal strategies of individual economic agents against a random, stochastically modelled, environment. Compare to the derivation of emergent physical phenomena, such as the distribution of gas molecules or atoms in a crystal, from first principles. A strength of the approach is that the preferences and environments of economic agents as well as emergent economic phenomena, can often be measured empirically, allowing for accurate calibration and validation. However, as opposed to the most basic physical laws, e.g. Newtonian mechanics, the mathematical formulation of micro-founded models requires stochastic optimal control theory, resulting in highly non-linear, typically infinite dimensional, equations.    The most accurate micro-founded approaches are heterogeneous agent models, where each agent is treated completely independently. However, as this increases the mathematical and computational complexity of the model, many implementations make compromises by either pre-aggregating agents' environments, leading to homogeneous agent models, assuming time stationarity or treating only one or two dependent variables simultaneously. Given these simplifications, many important, empirically observed economic phenomena are often left out, or can only be treated in isolation; for example, time stationarity means that intergenerational transfers are ignored, homogeneity between agents removes effects from economic inequality and treating dependent variables in isolation misses potential, non-linear influences between them.   This project will leverage powerful tools of stochastic analysis, in particular the language of coupled forward-backward stochastic differential equations (FBSDE) to give a rigorous, continuous time formulations of highly complex, dynamic, heterogeneous agent models. The FBSDE formulation gives access to efficient and cutting edge, NN based numerical methods, which offer robust, computational efficiency in the presence of increasing dimensionality. The proposal builds on promising, early stage work between the PL, economists and mathematicians at BI Oslo in which a robust, rigorous mathematical formulation of a simplified heterogeneous agent model has been obtained and accompanying numerical algorithm implemented. Funding is required to expand on this early work, extending the approach to genuinely applicable economic models and to build an open sourced code-base in order to attract a community of researchers, innovation users and policy influencers.   The concrete goals of the project are to produce a new mathematical framework and computational approach, tailored to the resolution of complex, heterogeneous agent models, exhibiting the following desirable properties:   Robust to a wide range of economically relevant extensions and variants of the model. Able to capture age, demographics and inheritance as mechanisms of wealth accumulation and transfer.  Are economically intuitive; i.e. lead naturally to  expressions of practical research relevance; for example sensitivity of model outputs with respect to control variables.  Require minimal mathematical literacy to implement, extend and apply to economics research. 

UKRI Gateway to Research · FY 2024 · 2024-11

We propose an innovative, novel, high quality research idea to address a key bottleneck in drug discovery. Our idea is to facilitate a discovery revolution by creating drug-like cyclic peptides inside cells via an exciting idea with significant potential to offer high reward. Cyclic peptides harbour significant potential for translation into drugs since they are ultra-structured despite their small size, non-immunogenic, bioavailable, while offering significant potential for cell permeability. However, their chemical synthesis is often slow and cumbersome, offering poor yields, and undertaken via unsustainable and toxic in vitro chemical means, making their creation and testing for drug discovery a slow and costly trial-and-error process. To address this major bottleneck, we will undertake three major aims: 1. A green and sustainable approach to cyclic peptide production - OaAEP1 is an asparaginyl endopeptidase (AEP) that catalyses peptide cyclisation in the plant Oldenlandia affinis, and the engineered C247A variant is employed in our recently established intracellular peptide cyclisation system (Tang & Mason, JACS Au, In press: https://pubs.acs.org/doi/10.1021/jacsau.3c00591). we will apply this biosynthetic approach to generate a suite of therapeutically relevant cyclic peptides of diverse size and structure (e.g. CP1, STFI-1, MCoTI-II, Kalata B1), and therefore validate the novel biosynthetic approach to cyclic peptide production. Chemical synthesis and folding of cyclic cysteine knotted peptides such as McoTI-II and Kalata B1 are known to be challenging and in-cell H2T cyclisation can guide correct cyclotide disulphide bridging. Deliverable: A novel biosynthetic approach will offer a convenient, safe, sustainable, scalable and low-cost alternative to existing chemical methods. 2. Optimising OaAEP1 for intracellular applications - We will engineer OaAEP1 by directed evolution to enhance i) solubility ii) ligase activity and iii) ability to function inside cells. This will be achieved by partially scrambling the amino acid sequence of OaAEP1 at solvent exposed positions to generate a 589,824-member library which will be screened for activity using split dihydrofolate reductase (mDHFR). Only ligation of mDHFR fragments will enable reconstitution of activity resulting in cell growth, with subsequent competition selection enriching the most soluble and active OaAEP1 library members. Deliverable: An engineered enzyme optimised for intracellular catalysis. The selection assay also allows rapid engineering of the enzyme by directed evolution to further modify attributes such as substrate specificity.

UKRI Gateway to Research · FY 2024 · 2024-11

The emergence and spread of antibiotic-resistant bacteria poses a significant threat to public health worldwide. Klebsiella pneumoniae is recognized as a particularly problematic species due to the spread of strains that are resistant to carbapenems (an important class of antibiotics) within hospital settings. Genes that confer resistance or virulence properties are often carried by genetic elements called plasmids. Plasmids can replicate and transfer independently between bacteria, which can account for how quickly these genes can spread across different bacteria. Moreover, different strains (and presumably different plasmids), are spreading in different parts of the world. ST11 is widespread in China, ST307 is one of the fastest spreading strains in Europe. Both of these strains attracted attention due to their high prevalence and ability to cause severe infections. Understanding the evolutionary mechanisms underpinning the emergence and spread (of both the bacteria and the plasmids), and the pathogenicity, of these strains is crucial for developing effective strategies to combat their spread and improve patient outcomes. For example - ST11 strains have been reported that contain plasmids harbouring both resistance genes and genes that make the bacteria more virulent. These plasmids have probably evolved through two different plasmids combining to form a hybrid, although little is known about the underlying mechanisms nor how common this phenomenon might be. In this project, we aim to investigate and compare the evolution of ST11 and ST307, and their plasmids, at a detailed molecular level. We will use advanced whole genome sequencing technology that provides the means to investigate both the genome of the strains themselves, and of the plasmids that carry resistance and virulence genes. By comparing the evolutionary trajectories, epidemiological patterns, and pathogenic potential of ST11 and ST307, we aim to identify key genetic determinants, processes and conditions that contribute to their success and persistence. This knowledge will enhance our understanding of the factors driving the spread of these clones and inform the development of targeted interventions to control their transmission, as well mitigating the risk from new emerging strains in the future. We will also use experimental evolution techniques to study what makes certain combinations of strain and plasmid successful, to what extent these resistance plasmids can be 'costly' to the bacteria under different conditions, and how free they are to transfer between different strains. Additionally, we will conduct virulence assays to assess the ability of these clones to cause disease. By analyzing their interactions with host cells and studying the factors that contribute to their pathogenicity, we can gain a better understanding of the mechanisms underlying their ability to cause severe infections, and thus contribute to the global efforts in combating antibiotic resistance and improving patient care.

UKRI Gateway to Research · FY 2024 · 2024-11

3D Bioprinting has recently emerged as a novel technology for developing customised, complex 3D biological constructs with great benefits for regenerative medicine. However, a significant challenge in implementing this technology is the lack of biomaterials (a key component of bioinks) that can simultaneously meet the desired bioprinting and scaffolding requirements such as printability, biocompatibility, biodegradability, and mechanical properties. Thus, we propose in this project a new generation of natural polymer-based bioinks having zwitterionic moieties in their structures. This zwitterionic modification is expected to enhance non-covalent interactions (e.g., electrostatic interactions), overcome the compromise among printability and other properties, and endow the hydrogel with biomimicry such as self-healing and strain-stiffening. Moreover, zwitterions are well-known to have exciting antifouling property which is needed for implants to protect them from the immunological response. The zwitterionic modification (carboxybetaine and/or sulfobetaine groups) of natural polymers (e.g., gelatin, alginate, carrageenan) will be realised by different approaches. Direct ink writing will be employed for the 3D printing of the developed zwitterionic hydrogel inks. We will explore different biocompatible crosslinking strategies (e.g., UV photo-crosslinking and ionic gelation) to allow high print resolution without compromising the biological properties. Besides zwitterionic modification, further enhancements in mechanical properties and printability will be explored by adding nanomaterials (e.g., cellulose nanocrystals or nano-clay) into the zwitterionic ink. The nanomaterial can reinforce the covalent network and form physical networks with the polymeric chains. The results of this project will generate extensive fundamental knowledge of zwitterionically modified bioinks for 3D bioprinting of advanced functional healthcare products.

UKRI Gateway to Research · FY 2024 · 2024-10

The doctoral training network IDEoPOP (International Dimensions and Effects of Populism) aims to study how the phenomenon of populism is related to world politics. While the global rise of populist political parties, governments and movements all over the world, from Hungary to India, from Italy to Mexico, from Turkey to El Salvador, has led to a great interest in the domestic implications of populism, its international effects have remained understudied. But populism impacts the foreign policy of single countries as well as international politics more broadly understood, and it is indeed frequently mentioned as one of the main causes for the crisis of the so-called liberal world order. The Doctoral Network IDEoPOP will consolidate the study of the international dimensions of populism as a research programme, shaping a new generation of scholars and developing policy-relevant insights on how to address the consequences of populism internationally. The focus will be on the ideational, institutional, diplomatic, and communicative international dimensions of populism. These will be addressed in four distinct Work Packages. The proposed doctoral network is driven by the following overarching research question: How are domestic and international politics related in populism, and how does populism impact international politics? As the phenomenon of populism is likely to continue affecting citizens' lives, state institutions, regional integration efforts, and the liberal international order in the years to come, a better understanding of its international implications is of utmost importance. Under the guidance of some of the leading scholars in this area, a new generation of doctoral researchers will be trained in the study of the international dimensions and effects of populism and will contribute to the Network's efforts at jointly addressing the overarching research question.

UKRI Gateway to Research · FY 2024 · 2024-09

This project aims to develop a sustainable way of degrading persistent pollutants from wastewater. It will do so by bringing different expertise into the project to develop new catalysts. This new technology has the potential to remove toxic and dangerous pollutants to the environment in a green way by using sunlight. The use of pharmaceutical compounds and pesticides has brought immense benefits to society. However, those chemicals consist in complex organic molecules that are made to resist for long periods of time in the bodies or the environment to be efficient, but the persistence of such components supposes a risk to the environment. They accumulate in water and cannot be completely removed by traditional technology wastewater treatment plants. Thus, they reach rivers and lakes and negatively affect the biota. In order to remove those persistent pollutants, it is necessary to use alternative solutions with enough energy to break their stable chemical bonds and accelerate their degradation. One option is using the called Advanced Oxidation Processes (AOPs). AOPs are based on generating radical molecules, such as hydroxyl or superoxide radicals. Radicals are very energetic and quickly react with any other molecule around them, including the molecules of persistent pollutants. During the reaction, the pollutant releases electrons to the radical. In this process, the different chemical bonds break and generate intermediate by-products until finally, only water and carbon dioxide remain as a product. The process of transforming the persistent organic pollutant into water and CO2 is called mineralisation. A sustainable method to generate radicals is using semiconductor materials. The semiconductors materials can be excited by sunlight to generate electron/hole pairs. Both can react with water and oxygen to produce radicals that can be used for the removal of persistent pollutants. The challenges with the current semiconductor materials are that they are not active with sunlight and that the pair and electrons recombine instead of being used in productive reactions. This project aims to investigate how to change the material structure of semiconductor materials. Dr Exposito is an expert in photocatalysis and by adding elements like phosphorous or oxygen to the structure, he will promote the generation of electron/hole pairs. Furthermore, to avoid recombination, we will combine the semiconductor materials with organic lipids. These organic lipids will contain iron that can react with hydrogen peroxide to produce extra hydroxyl radicals. In this way, some electrons generated in the semiconductor that would recombine will be used to generate radicals through the lipid membrane and avoid recombination. To understand how to attach the lipids and the behaviour, this project will promote collaboration with Dr Tse, a global leader in lipid membranes. The success of this project would contribute to directly to UN sustainable goals 6, Clean Water and Sanitation, and 14, Life Below Water, and indirectly to others like Sustainable Cities and Communities (11) or Responsible Consumption and Production (12). By proposing new, green ways of removing persistent pollutants from water, this proposal will contribute to a more sustainable UK's economy and society. The success of this research would bring new perspectives to the wastewater treatment sector, with societal and environmental impacts.

UKRI Gateway to Research · FY 2024 · 2024-09

Doctoral Training Partnerships: a range of postgraduate training is funded by the Research Councils. For information on current funding routes, see the common terminology at https://www.ukri.org/apply-for-funding/how-we-fund-studentships/. Training grants may be to one organisation or to a consortia of research organisations. This portal will show the lead organisation only.

UKRI Gateway to Research · FY 2024 · 2024-09

Doctoral Training Partnerships: a range of postgraduate training is funded by the Research Councils. For information on current funding routes, see the common terminology at https://www.ukri.org/apply-for-funding/how-we-fund-studentships/. Training grants may be to one organisation or to a consortia of research organisations. This portal will show the lead organisation only.

UKRI Gateway to Research · FY 2024 · 2024-09

Cannabis is a widely used drug globally, with over 200 million consumers. Despite its widespread use, there is lack of guidance to help people use cannabis more safely. For example, people who use alcohol can reduce their risks by adhering to safer use limits e.g., "do not regularly exceed 14 units per week". This research will develop new resources to help people record how much cannabis they are using (like calculating alcohol unit consumption) and recommendations for safer levels of use. These resources could help people to self-monitor their own cannabis use and make informed choices to reduce harm. They could also be used by people who give advice to people about their cannabis use in professional settings (e.g., doctors). Our understanding of how much cannabis is used and what cannabis contains is extremely limited in the UK. This research will also conduct regular surveys of the UK population and tests of cannabis samples. This will improve our understanding of the extent of cannabis use and its effects in the UK, and how this compares to other countries. This information could help policy makers to decide how to best to manage cannabis use. For example, cannabis use is prohibited as a criminal offence in the UK. This means that personal use of cannabis can lead to a prison sentence of up to five years, an unlimited fine, or both. Other countries have introduced different approaches. For example, people are legally permitted to purchase and use cannabis for recreational purposes in Canada. However, it is unclear which type of policy is best for reducing cannabis harms. Therefore, this research will make use of long-term data collected in the UK and other countries such as Canada. It will use this information to make predictions about how cannabis use and cannabis harms might change under current policy (e.g., prohibition) and alternative policies (e.g., legalisation). This will help policy makers in the UK and other countries to make decisions about how to best to reduce the harms of cannabis use.

UKRI Gateway to Research · FY 2024 · 2024-09

We live in the "Era of Mathematics" (UKRI, 2018), in which mathematics research has deep and widespread impact. Medical imaging is enhanced using the theory of inverse problems. Predicting sewage contamination in waterways after storms requires solving complicated systems of hydrodynamic equations. Machine learning tools are revolutionising data-intensive computing and, handled with proper mathematical care, have vast potential benefits for science and society. These are examples of the ongoing explosion in mathematical innovation driving, and being driven by, the analysis and modelling of data running through every aspect of life. Cutting-edge research now sits at the interface of data science and mathematical modelling. Methods and fields such as compressed sensing, stochastic optimisation, neural networks, Bayesian hierarchical models - to name but a few - have become interwoven and contributed to the delivery of a new domain of research. We refer to this research interface as "statistical applied mathematics". Established in 2014, the Centre for Doctoral Training in Statistical Applied Mathematics at Bath (SAMBa, samba.ac.uk) delivers leading research and training in this space. In the development of this bid, we have consulted widely with academic, industrial, and governmental partners, who consistently report a large and widening gap between demand and supply for highly skilled graduates. Our vision is to create a new generation of statistical applied mathematicians ready to lead high-impact, data-driven, mathematically-robust research in academia and industry. We will nurture a vibrant culture of cohort learning, enabling internationally-leading training in modern mathematical data science. A particularly important research focus will be the synthesis of data-driven methods with robust mathematical modelling frameworks. Tomorrow's industrial mathematicians and statisticians must understand when machine learning tools are (and are not) appropriate to use and be able to conduct the underpinning research to improve these tools by integrating scientific domain knowledge. This research challenge is informed by deep partnerships with a range of industry and government bodies. Our long-term partners such as BT, Syngenta, Novartis, the NHS, and the Environment Agency co-create our vision and our training. They are emphatic that we must address the urgent need for mathematical data science talent in this key strategic area for the UK economy. Many of our students will work directly on industry challenges during their PhD either in their core research or with internships. Our unique Integrative Think Tanks are the key mechanism for exploring new research ideas with industry. These are week-long events where SAMBa students, leading academics, and partners work together on industrial and societal problems. SAMBa graduates will be able to develop and apply new ideas and methods to harness the power of data to tackle challenges affecting society, the economy, and the environment. Our students will move into academia, providing sustainability to the UK's capacity in this field, as well as industry and government, providing impact through societal benefits and driving economic growth. Many alumni now hold permanent positions at leading UK universities and senior positions in a range of businesses. The CDT will be embedded within the University of Bath's Department of Mathematical Sciences, where 98% of the research is world leading or internationally excellent (REF2021). The CDT is supported by 58 academics in maths, with similar numbers of co-supervisors from industry and other departments. The centre will be co-delivered with 22 industry and government partners. A vital international perspective is provided by a worldwide network of 11 academic institutions sharing our scientific vision.