University of Manchester

UKRI Gateway to Research · FY 2025 · 2025-09

The UK aims to deliver 24 GW of new nuclear power by 2050, including a large proportion from new Advanced Modular Reactors (AMRs), with UK commitments to develop High Temperature Gas-cooled Reactor (HTGR) technology and worldwide interests in Molten Salt Reactors (MSRs). Nuclear graphite is vital for HTGRs and many MSR designs, making up approximately one-third of the overall build cost. Nuclear graphite is an export-controlled material currently manufactured overseas. Worldwide demand for nuclear graphite is rising, potentially leaving the UK without sufficient supply. Without UK investment in graphite, delivering net zero and future sovereign energy security are at risk. The UK led the world in graphite reactor technologies evidenced by the success of the Advanced Gas-cooled Reactor fleet, reaching the end of its lifetime by 2028. The extreme temperature demands of AMRs (~900 °C), relative to current nuclear reactors (450 °C), requires new innovations for graphite design and production to ensure future AMR operations remain safe and efficient. Developing an advanced lifecycle for nuclear graphite is key in delivering sustainable energy from AMRs. Neutron irradiation of graphite in reactor operations affects its mechanical performance and activates impurities creating long-lived radioisotopes resulting in a waste stream that requires geological disposal. Significant volumes of this waste already exist, and the expected AMR deployment will increase this substantially, costing the UK taxpayer £billions in storage and disposal, unless new graphite management strategies are developed. The time for graphite research investment is now. Data to underpin design code development, regulatory assessment, and operation of AMRs is scarce. Without significant UK investment in graphite knowledge and skills transfer, there is a substantial risk of losing many decades of experience which will be essential in supporting AMR developments. ENLIGHT offers a pathway for the UK to repurpose and upskill its unique position as a global knowledge and innovation centre for graphite. The overall aim of ENLIGHT is to design and produce sustainable graphite materials for AMR deployment and transform irradiated graphite from a waste stream into a valuable resource. ENLIGHT will deliver this aim across the following three intersecting research programmes: Sustainable Graphite - Develop processes for the decontamination, novel recycling, and reuse of irradiated graphite to minimise volumes arising from AMR deployment and provide design guidance on new materials. Graphite Selection & Design - Design new graphites to resist mechanical and neutron irradiation degradation in AMR conditions. Graphite Performance - Understand the behaviour of these new graphites in AMR conditions and maximise graphite lifetimes under irradiation, in unfamiliar AMR gaseous and liquid coolants. ENLIGHT will maintain the UK as world leader in nuclear technology vital for AMR fleets that now offer the greatest opportunity for energy independence and deep decarbonisation (i.e. process heat and hydrogen) to meet net zero targets. Our programme of research, collaboration, and skills development will expand and advance the UK graphite research community, nurturing the next generation of graphite engineers and scientists, essential to AMR technology advancement. ENLIGHT will also reduce the volume of graphite legacy waste and support decommissioning of current reactors. By working together with waste custodians, a graphite manufacturer, key industrial and regulatory stakeholders, ENLIGHT will determine what infrastructure and skills are needed to recycle graphite from decommissioned UK reactors.

UKRI Gateway to Research · FY 2025 · 2025-09

Lysosomal storage disorders (LSDs) are a group of rare genetic diseases affecting children, for whom there are almost no treatment options. Genetic mutations cause problems in the lysosomes of cells, leading to neurological problems, cognitive decline and ultimately death. Some of these processes are similar to those found in Alzheimer’s Disease (AD) and children are often referred to as having paediatric AD. Therefore, understanding the processes in these diseases will have broad implications for neurodegenerative research. This project aims to address if the immune system may play a fundamental role in exacerbating neurodegeneration in LSDs. A major advance of the past decade is the understanding that immune system plays a fundamental role in brain function in health and disease. At the cutting-edge of this research is understanding how the brain's borders, which are hubs of immune activity, drive brain disease. The specific aims of this research are to: 1) Experimentally target the brain's borders, called the meninges, to improve brain function in a model of LSDs. 2) Test whether novel anti-inflammatory molecules can protect from ongoing brain damage in models of LSDs. 3) Investigate biomarkers of CNS disease progression and treatment efficacy in a rare cohort of patients participating in an open label Phase I-II clinical trial. The potential applications and benefits are both specific and broad. This research programme has the potential to reveal new targetable pathways, understand underlying neurodegenerative mechanisms (not limited to LSDs), provide novel biomarkers to assess treatment efficacy and, crucially, enable experimental treatments in patients either in future or current clinical trials.

UKRI Gateway to Research · FY 2025 · 2025-09

Context: Metal-ligand multiple-bonding is a cornerstone of chemistry that underpins structure, bonding, reactivity, and catalysis. Isolated metal-ligand multiple bonds have been studied up to uranium, but transuranium-ligand multiple bonding is embryonic and dominated by actinyls, MO2n+ (M = uranium, neptunium, plutonium), and a single neptunium-bis(imido) actinyl analogue. Thus, it has not been possible to study transuranium-ligand multiple bonds in isolation, free of the strong inverse-trans-influence effects that dominate actinyls, but this is vital to do to assess actinide periodicity and answer enduring basic questions about actinide bond covalency.   Challenge Addressed: Historically, the paucity of experimental data has held the area back because computational predictions are very difficult to be sure of in a relativistic regime and conducting experimental research in this area requires access to specialist facilities. This project seeks to build on our preliminary result, joint with the European Commission Joint Research Centre at Karlsruhe (JRC), of a neptunium-mono(oxo) complex (Nature Chemistry, 2022, 14, 342-349). That study demonstrated that our approach works, and contrary to expectations, based on the commonly accepted picture of actinide bonding, this neptunium complex was found to be more covalent than the analogous uranium-mono(oxo) complex. This provides a tantalising hint that neptunium chemistry may prove to be even more diverse than the already rich uranium-chemistry and an opportunity to make a long overdue step-change in the area.   Aims and Objectives: Our hypothesis is that our preliminary result shows that the area can at last undergo a long overdue expansion, and that through our combination of people, facilities, approach, and ambition we can take the necessary step-change to sustainably elaborate transuranium science. Thus, our aim is to extend out, to realise new high-value transuranium-ligand multiple bonds and in-depth analyses to transform our understanding of actinide periodic trends and hence redefine the state-of-the-art. This will be achieved by delivering the following objectives with verifiable deliverables and milestones: Prepare a range of neptunium-group 16 multiple bonds. Prepare a range of neptunium-nitrogen multiple bonds. Conduct in-depth structural, spectroscopic, magnetic, and computational characterisation.   Benefits: This work will make use of the world-leading JRC and KIT Light Source facilities to give unprecedented insight into transuranium electronic structure, bonding, and periodic trend data, which will transform our understanding of these elements and their chemical bonding. It is widely accepted that advances in separations science requires a better understanding of chemical bonding as extractant selectivity originates from covalency differences. Hence, in time the framework of understanding that this work generates might find use in generating new ideas to addressing future separations, e.g. waste clean-up. This project benefits from having a Senior Experimental Officer at the UoM who is a transuranium specialist. His placement at the JRC will promote mobility, putting a member of technical staff at the heart of delivering internationally leading science, thus developing his career in-line with the progressive UKRI agenda to realise greater research prominence and recognition for UKHE technical staff. He will bring best practice from the JRC back to the UK, enhancing the UK’s skills and knowledge for handling radionuclides and glove box techniques, addressing a looming, recognised skills-shortage in this area by disseminating that know-how to new generations of nuclear workers through our Centre for Radiochemistry Research (see LoS). This will benefit UK science and key nuclear sector stakeholders against fierce international competition.

UKRI Gateway to Research · FY 2025 · 2025-09

My PhD explored the complexities of everyday migrant family life, through a critical intercultural lens. In doing so, I provided an important contribution to knowledge by presenting a deeper understanding of the intercultural intergenerational complexities within migrant families. Although focusing on the case of Chinese families in the UK, my findings have value beyond the UK-Chinese communities and can contribute to understandings of migrant families in general. This fellowship will provide me with the means to publish my findings which will allow me to make a contribution to the fields of intercultural communication, migration and family, within the broader field of education. I will be consolidating my PhD research and establishing my career as a researcher on migration and family within the fields of intercultural communication and education. I will spend half of my time working on the dissemination of my findings through publication of written work. I plan to work on two journal articles and one book chapter. The two journal articles will highlight the conceptual and empirical contributions of my PhD, and the book chapter will highlight some implications for practitioners who are supporting migrant learners and their families. By the end of the fellowship, I aim to have had one article accepted, and one article submitted. I also will have submitted my book chapter. I will spend most of my remaining time on other forms of dissemination and networking activities. I will attend and present at academic conferences and events to discuss the findings from my PhD. Through these events, I will be engaging with researchers within my field, and making an impact by sharing my findings and conceptual contributions. Through these events, I will also be able to develop my networks and open doors for possible future collaborations. Apart from academic networks, I will also be disseminating my findings with local Chinese communities which were the focus of my PhD. These dissemination activities through workshops with families, and talks with community groups, will be done through community languages. This will allow for impact with marginalised communities who otherwise would not have access to academic research. These community talks aim to support migrant families who may be dealing with intergenerational communication challenges. I will also be building networks with local community groups which are supporting new Hong Kong migrants who have arrived in the UK over the past four years. Since 2021, over 130,000 Hong Kong residents have migrated to the UK through a humanitarian visa route. Through my engagement with this community, I have become aware of their needs, which are similar to that of my PhD participants when they first arrived in the UK. I will share my work with these community groups with the aim of supporting new migrant families which will create immediate social impact. Lastly, I will be working on a larger funding proposal to further continue my work on migrant family issues, which will further establish my career as a researcher. The networks I make with Hong Kong community groups, in addition to a trip to Hong Kong to understand the context, will support my writing of a larger proposal on the settlement experiences of Hong Kong BNO migrants to the UK. This will be submitted by the end of the fellowship.

UKRI Gateway to Research · FY 2025 · 2025-09

The National Materials Innovation Strategy has highlighted developing a digital thread through materials discovery, manufacturing, in-service performance and (re)use – aka Materials 4.0 - as the highest priority to realise accelerated scientific and economic benefit across the UK materials supply chain.  This short proposal will produce three case studies to underpin future programmes and investment for delivering Materials 4.0, empowered by AI, to ensure innovative global leadership for the UK in this vital area. AI is key tool in delivering Material 4.0. The widespread adoption of emergent detailed data capture and control capability, alongside AI tools and techniques, will revolutionise the pace and impact of materials’ discovery, optimisation and automation across many industries from national infrastructure to defence. To achieve this, the AI needs include relevant data access (historic and future), applying materials-informed machine-learning and language models, to forecast emerging materials innovation. This is underpinned by automated data capture, storage and analytics that include the AI-driven characterisation of materials and properties, and identify structure-property relationships that can be exploited. A UK transition to Materials 4.0, extracting the transformational power of AI, must be cohesive for maximum impact, facilitating the integration of digital tools and data development across diverse industries and sectors. The Henry Royce Institute (Royce), the EPSRC’s national materials institute, aims to work with the materials community to establish the framework for delivering the necessary skills, best practices and infrastructure. This  includes consideration of a national capability (e.g. a UK Materials Informatic Centre) to drive cross-sector change and draws on inspiration from other sciences (e.g. European Bioinformatics Institute) and countries.  Our initial focus will be on automating materials data capture, storage and analytics and integrating this into an exemplar ‘design-to-device’ supply-chain for data-driven materials discovery and performance. This includes the exploitation of open-source materials datasets and materials-domain-specific language models that Royce has collated for the materials community via its new Digital Materials Foundry (launched 16 May 2025: https://www.royce.ac.uk/programmes/digital-materials-foundry/). This aligns with §1.2 of the UK government’s AI Opportunities Action Plan. We will exploit materials-informed machine-learning and big-data analytics for materials and property prediction. This will be done through incorporating AI enabled surrogate model approaches to bridge numerical and analytical models that cover multiple length scales up to component/device level; this includes their interface into manufacturing needs where our centre will ultimately connect into wider programmes and challenge-led activities such as Made Smarter. Royce has commissioned work to develop a framework and implementation strategy for a national, connected framework that will accelerate the widespread adoption and integration of Materials 4.0 across the UK’s materials innovation ecosystem and industrial supply chain.  This proposal will provide three underpinning case studies to understand the architecture needed for Materials 4.0.  These cases will focus on (1) AI driven automation of data collection and analysis for facilities, (2) development of FAIR data infrastructure for autonomous energy materials discovery, and (3) optimising a factory production line’s efficiency using AI analysis of historical data.

UKRI Gateway to Research · FY 2025 · 2025-09

Chiral NanoGraphene for multifled Semiconductor Security - ChiNGS   This project aims to pioneer a new frontier in semiconductor device security by harnessing the power of chiral nanographenes—specially engineered, twisted carbon molecules with unique electronic and optical properties. While today’s hardware security often relies on complex software or circuit design, our approach seeks to embed protection into the very materials that form electronic devices, making them inherently resistant to tampering, counterfeiting, and hacking. Led by researchers at the University of Manchester, UK, in partnership with the University of Cologne, Germany, our collaborative team will design, synthesize, and test chiral nanographenes as advanced security elements. By integrating these molecules onto atomically thin platforms—such as graphene and hexagonal boron nitride—we aim to produce prototype devices whose electrical and optical “fingerprints” are impossible to clone or forge. These fingerprints can be used as physical unclonable functions (PUFs), providing robust means to verify authenticity and detect intrusion directly at the hardware level. Cutting-edge fabrication techniques, including thermal scanning probe lithography, will allow precise placement and manipulation of these molecules, while advanced characterization tools will assess their performance under real-world electronic conditions. This multidisciplinary effort will also facilitate training for young researchers, knowledge exchange across borders, and engagement with industry and the wider public through workshops and outreach. Our vision is to lay the scientific and technological foundation for a new generation of secure-by-design electronics—where materials science and device engineering converge to deliver tamper-proof, resilient hardware. The outcomes will not only deepen our understanding of chiral nanographenes and their remarkable properties but also open crucial pathways for enhancing national security, digital trust, and the safety of future digital infrastructure.

UKRI Gateway to Research · FY 2025 · 2025-09

This UKRI Fellowship renewal will continue to support my development of new scientific expertise at Keele University which interfaces chemistry and biology. The overarching goal of the research is to establish efficient technologies to provide biologically important carbohydrates. Such biomolecules are positioned to modulate or mediate a huge variety of biological processes and as a result there is a sustained interest from the scientific community around the synthesis of carbohydrate structures. I will harness flow biocatalysis to enable controlled and reproducible production of the building blocks essential to carbohydrate biosynthesis, sugar nucleotides. Secondly, I seek to expand the frontier of glycoconjugate chemical biology through exploration of a novel prodrug approach, combining sugar nucleotide donors and nucleoside analogues. In undertaking this research, I will adopt a multidisciplinary approach consisting of a fusion between traditional organic chemistry, biocatalysis, the evolving field of synthesis automation, and the innovative field of chemoenzymatic synthesis. This combination will facilitate the development of a faster and greener approach to explore biologically relevant carbohydrates. This is a rapidly evolving worldwide field which is currently underrepresented in UK science. The important materials provided by the technology and knowledge developed during this Fellowship renewal will be used to probe underpinning carbohydrate biology connected to disease and aid in the design and development of new therapeutic strategies.

UKRI Gateway to Research · FY 2025 · 2025-09

Overview: Deuterose is a new biotechnology for the clean manufacture of speciality isotopically labelled sugars. These sugars are essential for a range of research and medical applications, but their high cost makes them prohibitively expensive. This new technology will supply isotopically labelled sugars for an order of magnitude reduced cost, thereby enabling a diverse array of frontier bioscience and new diagnostic techniques to be developed. Ultimately this will accelerate life science research and lead to breakthroughs in diseases such as Alzheimer’s and cancer more quickly. The project is highly commercialisable, and will lead to economic benefits for the North West, and further afield. Furthermore, the technology is more sustainable than current methods and presents scope for developing a large portfolio of green isotopically labelled compounds to meet growing demand. Aims: The aim of this BBSRC FoF application is to progress Deuterose from Technology Readiness Level (TRL) 3-4 to TRL6. By Month 24, Deuterose will have been commercialised for the production of a core product (deuterated glucose), or a clear plan will be in place to enable commercialisation of this process soon after. In order to achieve these goals, several technical and commercial milestones must be met. Key to these are: (i) Demonstrating the use of the technology to support the wide community of potential end users. (ii) Scaling-up to a commercially useful scale to meet estimated current market demand (iii) Building a business plan based around market research with the aim to license or spin-out. The end-user engagement represents a major source of added value for this FoF application, as it will enable a number of fundamental life-science research projects to progress immediately, benefitting from the low-cost isotopic materials being made in the project. Approach: Our team has a broad range of expertise to meet the demands of this ambitious project. We have extensive experience of biomanufacturing and enzyme technology, sugar chemistry, and isotopic labelling. Importantly, the lead and co-lead have track records of IP development and translation of novel biotech research. We have also assembled a very wide group of project partners and collaborators – from end-users (such as the STFC-funded ISIS Neutron and Muon Source) to experts in scale-up of enzymatic processes for commercialisation. Our team also has expertise in MRI imaging, as this is an emerging area where our technology could rapidly make a transformative difference. Outcomes: The Deuterose technology is a powerful demonstration of the utility of enzymes for clean manufacturing in the speciality chemicals sector. Based in the thriving biotech innovation community in Manchester, Deuterose will be able to grow rapidly to meet the demands of the UK and international isotope user groups. This will, in turn, lead to job creation in the region, as well as additional benefits through fuelling and enabling front line science. By the end of the project, we aim to establish Deuterose on a clear trajectory for growth as a licensed technology, or spin-out.

UKRI Gateway to Research · FY 2025 · 2025-09

Radiotherapy (RT) is a vital treatment for around half of all cancer patients. RT delivers targeted radiation to the patients’ tumour, and incidentally to surrounding healthy organs, which can cause side-effects. To reduce the risk of these side-effects, treatments are optimised for each patient based on their detailed medical images to maximise the dose to the tumour whilst minimising the dose to surrounding healthy organs, creating intricate spatial ‘dose distributions’. Significant improvements in treatment techniques have resulted on improved patient survival following treatment. However, this also means more patients are experiencing tumour recurrence or new tumours near the original site. The future for these patients can be bleak, with limited treatment option: surgery is often not possible due to frailty, and chemotherapy typically ineffective. Receiving a new course of RT, also known as reirradiation (reRT), is emerging as a promising treatment. However, a major challenge hinders the wider use of reRT: we have a limited understanding of how healthy organs react to multiple rounds of radiation. For example, it is not clear how much total radiation dose organs can tolerate before they cease to function properly, especially as some organs can partially heal from previous radiation. These gaps in knowledge, together with severe side effects seen with older techniques, make doctors cautious about recommending reRT. To enable safe reRT for more patients, it is essential to estimate the total dose that the patient’s anatomy receives. This requires projecting the radiation from previous treatment(s) onto the current patient anatomy, a process called dose mapping.  Dose mapping relies on aligning corresponding anatomical features visible in the medical images using advanced image-matching techniques known as “deformable image registration algorithms”.  However, patient anatomy can change drastically between treatments, due to factors like aging, effects of previous radiotherapy and/or surgeries. Current methods cannot effectively manage these complex changes and they do not consider the different levels of accuracy required to map intricate dose distributions. These shortcomings result in inconsistent dose estimates, making it difficult to understand the total doses organs can handle and how dose affects organ function. Finally, current methods use statistical prediction models that overlook important factors like the location and timing of radiation treatment. These models are not designed to understand cause-and-effect relationships (unlike causal analysis), so their usefulness for decision making and personalising treatment plans is limited. This proposal aims to create advanced methods for reliable dose mapping and to introduce (spatiotemporal) causal analysis techniques. This will help to build knowledge on radiation limits to guide future reRT. The aim will be accomplished by achieving the following objectives: Develop dose mapping algorithms capable of handling significant anatomical changes. Create dose mapping algorithms that incorporate intricate dose characteristics. Adapt and implement spatiotemporal causal analysis techniques for reRT. Generate evidence on acceptable cumulative dose levels below which the risk of developing serious side-effects in the reRT setting is clinically acceptable. The tools developed in this project will ultimately improve safety of reirradiation, enhancing long-term outcomes for many cancer patients by accurately mapping previous doses onto current anatomy and considering the spatial and temporal aspects of reRT within causal analysis. These innovations will reduce the risk of severe side effects and support more effective treatment planning. Furthermore, the generation of high-quality evidence will guide clinical practice, benefiting patients worldwide.

UKRI Gateway to Research · FY 2025 · 2025-09

The generation of mature blood cells and haematopoietic stem cells (HSCs) has been a longstanding goal in stem cell biology, developmental biology, and biotechnology due to their critical roles in clinical applications such as bone marrow transplantation, transfusions, and cellular immunotherapy. A crucial component in blood cell development is the haemogenic endothelium (HE), a rare and transient endothelial cell population found in the embryonic vasculature. During the Endothelial-to-Haematopoietic Transition (EHT), HE cells lose their endothelial characteristics, activate haematopoietic transcriptional programs, and transform into blood cells. This process is essential for haematopoiesis, providing a direct and practical target for generating all blood cell lineages. Pluripotent embryonic stem (ES) cells and induced pluripotent stem cells (iPSCs) offer promising starting points for achieving this goal. However, their differentiation into specific blood cell types remains inefficient, requiring labor-intensive protocols and extensive culture to produce functional cells. These protocols often depend on enriched HE-like populations, where true HE cells are scarce. This scarcity limits our ability to fully understand the EHT process and hampers the development of efficient, scalable protocols for generating therapeutic blood cells. To address these challenges, we successfully established a novel murine HE (mHE) cell line using transient expression of a unique combination of transcription factors. This cell line demonstrates robust expansion capacity and undergoes definitive haematopoiesis upon withdrawal of ectopic gene expression. The mHE cell line generates multi-lineage haematopoietic progenitors and mature blood cells, as demonstrated through flow cytometry, colony-assays, gene expression profiling, and cytospin analysis. This mHE cell line provides an unprecedented opportunity to study EHT with enhanced precision and scalability. Using this system, we plan to perform genome-wide CRISPR screens to identify new master regulators of the EHT process in an unbiased manner. Single-cell RNA and chromatin accessibility multi-omics will enable detailed mapping of the dynamic molecular regulation of EHT, revealing gene regulatory networks (GRNs) that drive the activation of distinct cell fates. Additionally, (phospho)proteomics will provide the first insights into the dynamics of protein expression and signalling pathways underlying EHT. The resulting data will serve as a comprehensive resource for researchers studying blood development. This research will also inform future strategies to manipulate haematopoietic lineage choices, offering a comparative basis for future enhancements of generation of therapeutically relevant blood lineages. Developing similar human HE (hHE) cell lines would be a transformative step in the field, enabling scalable platforms for producing blood cells for therapeutic applications. The work outlined here will serve as a blueprint for the development, characterization, and utilization of novel human HE cell lines. The long-term impact of this research will be the creation of robust human platforms capable of generating modified cells for transplantation, transfusion, and cellular (immuno-) therapies, ultimately paving the way for innovative therapeutic interventions.

UKRI Gateway to Research · FY 2025 · 2025-09

This application from the University of Manchester is to replace an obsolete camera on a BBSRC-funded Glacios cryo-electron microscope with a Falcon4i camera and Selectris energy filter. This will enhance our capabilities and transform usage with higher quality images and more efficient data collection and will make cryo-electron tomography data collection possible. Cryo-Electron Microscopy (Cryo-EM) provides us with details of tissue and cellular structure, as well as directly imaging proteins or multi-protein complexes (e.g. enzymes, biological motors and viruses) too small to be detected by light microscopes. It was the advent of the direct electron detector technology that provided Cryo-EM with the high sensitivity required to image proteins at atomic resolution. Newer detectors, such as the Falcon4i are even more sensitive, to enable imaging of proteins that were previously too small or flexible. Another enabling technology in Cryo-EM, is the development of imaging filters, such as the Selectris energy filter, which improves contrast in the images. At the University of Manchester, Cryo-EM supports a wide portfolio of BBSRC funded projects in addressing their central research questions. Moreover, to understand the function of proteins, or complexes in their native cellular or tissue environment many of these projects are now extending to cryo-electron tomography (Cryo-ET), where a new system is needed to image these thicker samples. Our current microscope, a Thermo Fisher 200 kV Glacios instrument was purchased in 2020 with BBSRC funding. The instrument has been very productive in terms of usage, publications and supported grant applications. We have also produced 20+ high resolution structures from Manchester research groups including fibres/fibrils, molecular machines, viruses and a range of individual proteins. The instrument was designed to be upgraded in a modular fashion, and we are now at a point where the original Falcon 3 camera is incompatible with the newest versions of the software used to operate the microscope and for tomography and thus the detector will soon be obsolete. The Falcon4i-Selectris would continue to enable high-profile research at Manchester using Cryo-EM including: Studying structural matrix proteins involved in inflammation and tissue integrity, (e.g. defective mucosal surfaces in the gut.) Investigation of how enzymes work and then manipulating them for biotechnology or bioremediation applications. Understanding how proteins are made and processed. Some proteins can ‘mis-fold’ and cause disease (e.g. in Alzheimer’s). Investigating how proteins in membranes can sense mechanical pressure and transport ions. Developing new technology based on virus-like particles for new vaccines, Mass Spectrometry for protein separation and Nanobody-based tools for Cryo-EM. The investment in a modernised instrument will amplify these projects and uplift the initial BBSRC investment from 2020. The University of Manchester recognises this by contributing 20% funding towards the upgrade purchase along with associated estates costs to refurbish the Facility with field cancellation hardware and a new control room. Additionally, the University has already funded a high-pressure freezer for preservation of cell and tissue samples, upgraded the University supercomputer with a dedicated GPU bank and provide an expert Research Technology Professional (RTP) to run projects through the instrument within a core facility platform.

UKRI Gateway to Research · FY 2025 · 2025-08

Through a legal review and contextualised case studies from 20th and 21st centuries Britain and France, DeterAge aims to offer the first history of border policing which focuses on how age has become increasingly important to migration processes and experiences. The use of chronological age to categorise populations is one of the key aspects of the modern state (Scott 1999). Its precise determination is essential to a wide array of fields including criminal responsibility and medicine (Schmeling and Black 2010) and has become central to Global North migration regimes. From the French Constitutional Court’s decision in 2019 to validate the use of bone age tests, to the launch of an Assessment Board by the British Home Office in 2023, it is now one of the most pressing issues in British and French public and policy debates around migration and asylum. Advocacy groups and practitioners, from human rights organisations to hospital ethics committees, as well as scholars in disciplines as diverse as social anthropology or radiology have frequently questioned the validity of assessment methods and their impacts on migrant well-being (Alshamrani 2019, Bialas 2023, Paté 2023). These discussions, whilst valuable, often lack a historical dimension that could help better understand the complex situations and processes that shape experiences and responses to displacement. DeterAge will examine why and how age-based border policing was produced by British and French policy makers, implemented by law enforcement and their intermediaries, and experienced by young migrants. Britain and France provide paradigmatic cases to examine how liberal democracies have used age in border policing. They were among the first countries in the world to create age measures that targeted migrants, implemented stricter age control during and after the independence of their colonies, and are now widely using age determination as part of migrant and refugee screening. Building on understandings of the border as an increasingly mobile framework (Shachar 2020), DeterAge will historicise the often-unquestioned age standards that continue to shape laws, humanitarian responses, and migration experiences. After reviewing how age has been included in the main immigration laws from the restrictions of the end of the First World War to the generalisation of biometrics and securitised environment today, this project will focus on three case studies: two historical case studies led by the PL on (i) policing young refugees in the aftermath of World War 2 and (ii) family reunification in the decolonisation era; and one anthropological case study led by the RIA on (iii) age-disputed young migrants and their support networks in Manchester and Marseille today. Bringing together a long-term legal review with three case studies will allow for an approach that encompasses wide-ranging spaces, techniques, and experiences of border policing during key periods of British and French modern migration history. Expanding ongoing collaborations with two key protection actors, Médecins Sans Frontières (MSF) in France and the Greater Manchester Immigration Aid Unit (GMIAU) in Britain, DeterAge will produce wide-ranging publications and outreach activities to inform current debates, including a monograph and three peer-reviewed journal articles, a practitioner-oriented workshop, a policy report, public events, and a guide for young migrants. Its results will be disseminated to a wide audience of scholars and stakeholders that engage with health and well-being in the context of migration and asylum, as well as young migrants themselves and their networks.

UKRI Gateway to Research · FY 2025 · 2025-08

Current trusted research environments (TREs) and their capabilities are designed for secure and efficient handling of real-world structured data. While this often supports rich data analysis, the focus on structured data types restricts the research space and questions we can answer.  For example, often missing from the data landscape is free-text narrative, which is a key data source in healthcare. Valuable clinical information is often recorded only in notes and reports, with some specialties and services almost completely documenting care in text (e.g. mental health). Research in these domains may therefore be limited to an incomplete structured data environment, which in turn may result in lack of understanding and progress, and exasperation of inequities (e.g. patients with certain diseases being less likely to benefit from healthcare data analytics).  A key reason for free-text data not being hosted in TREs is its inherent sensitivity and unexpected risks to patient privacy. Manual text de-identification is impossible to scale to accommodate different settings and numbers needed for most analytics purposes. Several efforts have been invested in automated anonymisation of free text data, but there are still no accepted protocols, techniques or metrics to characterise and quantify privacy preservation of free-text data. The associated, unquantified risk has consequently resulted in real-world free-text data rarely, if ever, being hosted within TREs.  Synthetic text collections are emerging as an alternative and trustworthy solution, where data is generated through an AI process that ensures both task-specific data relevance and privacy. In this pilot we will explore embedding of synthetic healthcare text generation and its use into existing TRE infrastructures developed in DARE UK Phase 2. This will expand the current TRE capabilities with a new modality in healthcare. To ensure fidelity and representativeness of synthetic text, we will use de-identified real-world data from different settings as a guide for federated text generation. Built in this process will be the use of differential privacy to ensure patient confidentiality. A key outcome of the project will be a methodology and prototype that provides a trusted and reliable approach to generation and validation of clinical free-text data. We will co-develop with clinicians, patients and regulators an early technical validation framework consisting of privacy validation, text quality assessment (with reference to a given clinical or cohort specification) and early testing of the usefulness of generated data for analytics tasks. As a demonstrator use case, we will apply the framework to assess the quality and the value of generated text for federated learning for downstream language modelling tasks in the domain of cardiology. We will organise a series of “validatathons” with patients, clinicians, data scientists and regulators to explore the challenges, opportunities and acceptance for synthetic free-text data.  We will use existing, publicly available real-world de-identified datasets to generate different collections of synthetic data. We will then use these collections to train models to optimise patient cardio-workflows and compare the outcomes with the workflows generated from the original dataset. This way, we will use “synthetic data as a risk management approach for testing different analytical capabilities within TREs”, mitigating patient privacy risks. Generated data will be represented using adapted common data models for sensitive data (e.g. OMOP), with RO-Crate used to represent additional meta-data describing the synthetic generation process and data provenance.

UKRI Gateway to Research · FY 2025 · 2025-08

At the start of an outbreak of a respiratory pathogen with pandemic potential, countries typically have plans to run "First Few X" (FFX) studies that capture key epidemiological features of the first X cases detected as well as potentially infectious contacts. Typically the cases involved will number in the hundreds or thousands, although this will depend on factors such as available resources for case ascertainment and policy prioritisation of the outbreak in question. Important answers to obtain from these data include estimation of: overall severity and transmissibility of the pathogen; timescales associated with duration of symptoms and infectiousness; timescales associated with transmission and population-level exponential growth; and specific risk-factors (e.g. age, sex) as well as co-morbidities (e.g. enhanced risk for sufferers from chronic conditions such as diabetes). In well-resourced contexts, particularly larger, richer countries, there will typically be significant computational resources available to run any available algorithm, as well as large teams of analysts from government, academia and industry with highly specialised skills available to create bespoke analysis plans and code. Neither of these can be guaranteed in resource-poor contexts, for example smaller or less wealthy countries. The main aim of this project is to develop a suite of analytical methods, together with suitable documentation, that can provide the required answers in the hands of analysts with generalist epidemiology and / or public health training and without access to significant computational resources. As an additional benefit of developing such methods, it will become easier for all countries to pool data from their respective FFX studies. In general, well-resourced jurisdictions will have their own priorities for analyses to carry out to inform their specific policy objectives, but these are not guaranteed to permit shared analyses. Indeed, even relatively simple meta-analyses such as those of household transmission studies often do not find much consistency in analysis protocols and reporting, making it hard to improve statistical power through combination of studies. Having a standard, quick methods suite will mean that every FFX study can be run through comparable analyses with negligible extra computational and staff cost. We will therefore also provide tools for meta-analysis of FFX studies analysed using the methods developed. The software packages released will be designed to interface naturally with the World Health Organisation’s Go.Data framework for management of complex outbreak data (see https://www.who.int/tools/godata). The open-ness of this framework will enable other data management tools to be developed to interface with the analytical methods. Another important question relates to design and protocols for real-time adaptation of FFX studies, for example the relative balance of serological, swabbing, and symptomatic data collection. This project will contribute to the ongoing process of design and refinement of design of these studies through providing simulation tools and insights from new analyses of existing FFX studies including those from Albania, the UK, and Kazakhstan.

UKRI Gateway to Research · FY 2025 · 2025-08

Industrial policy is back in vogue among policy makers today, encompassing a broader range of goals to address critical  global challenges such as economic decarbonization, territorial inequalities, securing domestic industries, and adapting to  rapid technological advances in AI and digital innovation. These interventions are connected to many of the future global  challenges identified by Policy Horizons Canada. This 'new' industrial policy is a potentially powerful instrument to  reimagine state-government-society relations. This Knowledge Synthesis will analyse academic and policy literature  alongside industrial strategies in order to identify the state of knowledge, strengths and gaps and research data (Objectives 1  and 2). The analysis and findings will inform a co-developed conceptual framework to support knowledge mobilization  (Objective 3). By translating research findings into accessible frameworks, the project will support policymakers,  stakeholders, and researchers in making informed, evidence-based decisions. This framework will serve as a foundational tool for future research and policymaking, essential for crafting impactful and adaptable industrial policies that meet today's  complex needs. By analyzing academic and policy literature and recent industrial strategies from Canada and the UK, the research will assess  whether policy goals align with academic findings. Additionally, the project will examine data collection and analytical  techniques used to support industrial policy, focusing on recent advancements in place-based analysis. Our co-developed  conceptual framework will distill key findings into a cohesive understanding of new industrial policy approaches, governance  mechanisms, and research needs. This knowledge synthesis will assist policymakers and researchers to develop more  inclusive, effective, and future-ready industrial policies. Led by Tamara Krawchenko, an internationally recognised expert in comparative public policy and regional development,  and Philip McCann, a renowned spatial economist, the project benefits from their combined experience advising governments and leading high-impact research across Canada, the UK, and internationally. Their contributions are complemented by  graduate research assistants who will receive hands-on training in literature review, scoping, and knowledge synthesis,  actively participating in the development and presentation of the project's outputs. Knowledge mobilization for this project  will be supported by the Organisation for Economic Co-operation and Development, the Transition Accelerator's Centre for  Net Zero Industrial Policy (Canada) and The Productivity Institute (UK).

UKRI Gateway to Research · FY 2025 · 2025-07

Semiconductor materials underpin all five ‘technologies of tomorrow’: quantum, AI, engineering biology, semiconductors and future telecommunications. For example, the development of mm-wave/terahertz sources for 6G telecommunications relies on III/V compound semiconductors. The quantum computing architecture at the highest maturity level is based on donors in silicon. Today’s most pressing societal challenges, such as net zero, also require semiconductor development. For instance, wind and solar technologies require high-power operation, whereas digital ‘smart’ devices need to improve efficiency to reduce energy consumption. However, performance gains for semiconductor devices are slowing, as transistors reach fundamental molecular/atomic limits. To achieve smaller, faster, smarter, more energy-efficient devices, advanced functional materials, such as graphene, 2D materials, III-V nanowires, are therefore essential. Topological materials form potential building blocks for all 5 technologies.  Examples include topological insulators (TI), which are insulating / semiconducting in the bulk with topologically-protected conductive surface states, and Dirac semi-metals (DSM) that are 3D analogues of graphene. They can therefore host spin-polarised surface currents, which act like a tramline – they travel in one direction set by their spin with less heat and resistance. This makes them promising candidates for low-loss electronics, spintronics and quantum technologies. However, they are still at a low maturity level, requiring further understanding and control of their optoelectronic properties. This proposal aims to address this issue by developing novel terahertz spectroscopy and microscopy techniques to examine the optoelectronic properties of topological insulators for technological applications. When operated in the far-field, terahertz spectroscopy can provide information on the average electrical conductivity, carrier density and carrier mobility in the material on mm-length scales. By utilising this technique, we have extracted the bulk electronic properties of topological insulator thin films and Dirac semi-metal nanowires. We have demonstrated that they can generate THz radiation, making them promising candidates for development of THz sources. By altering the properties of the photoexcitation beam, we can also control the emitted THz radiation, optically-switching between broadband and narrowband operation and tuning the peak emission frequency. This exciting behaviour is directly related to their topological nature, with polarisation control provided by spin-polarised currents at the surface. We will therefore focus on developing controllable THz sources from topological insulator thin films with the following objectives: 1) To examine the local THz photocurrent emission on TI and DSM nanostructures. 2) To control / enhance their THz emission via improved material/device design. 3) To develop a prototype THz source based on TI / DSM NWs for on-chip integration. To optimise these materials, we will measure their electronic and emission properties, as we change key growth parameters, such as doping and growth temperature.  We will also investigate how properties on the nanoscale influence performance, such as defects from growth, changes in crystal structure and localised doping. To achieve this, we have established a national near-field microscopy facility that operates across the visible to terahertz wavelength range. When operating in the THz range, it enables us to map the surface-sensitive electrical conductivity, reflectivity and absorption with <30nm lateral spatial resolution. This will enable us to cross-correlate the emission performance of our topological materials with their local electronic properties and engineer these materials at these nanoscale. Once optimised, we will fabricate prototype THz sources from these materials and assess their performance in real-world applications, such as a communications testbed and imaging setup.    

UKRI Gateway to Research · FY 2025 · 2025-07

The BD FACSDiscover S8 cell sorter with BD CellView Image Technology and BD SpectralFX Technology (hereafter referred to as the Discover S8) is a cutting-edge instrument that combines spectral cytometry and multicolour image-based cell sorting. The Discover S8 is not the only spectral flow cytometer on the market capable of cell sorting; however, by adding image-based sorting capabilities the Discover S8 represents a first-of-its-kind machine. As such the Discover S8 offers researchers the ability to sort and collect well defined cell populations based on cell imaging; enabling researchers to isolate cells by characteristics that were previously impossible to define on a conventional flow cytometer. Equipping globally renowned researchers within the University of Manchester (UoM) with this cutting-edge piece of equipment will drive forward research in priority areas including immunology, neuroscience, developmental biology, microbiology, fungal infection biology, and environmental sciences. The Discover S8 allows UoM researchers to isolate cell populations hitherto impossible to isolate, including cells with defined morphology or cell structures, distinct sub-cellular location of fluorescence, co-localisation of fluorescence signals, and/or cell doublets. These populations will be utilised in a plethora of downstream applications including transcriptomics, proteomics and metabolomics, in vitro cellular assays, and in vivo transfer approaches to provide novel insights in molecular and cellular biology - driving forward research across a broad spectrum of biosciences.   Underpinning this application is a consortia of UoM researchers, from a breadth of research disciplines; this breadth highlighting the step-change in technological advancement offered by the Discover S8. By becoming integrated into a well-supported and managed UoM core facility, acquisition of a Discover S8 will immediately enable consortia members to address, as yet impossible to answer questions. For example the Discover S8 would allow sorting of cells in which fluorescence signal is localised to the nucleus compared to the cytoplasm, enabling interrogation of the consequences of protein function in distinct locations. Alongside this, the Discover S8 will function as a conventional spectral flow cytometry sorter enabling the highly in-demand sorting capabilities of the UoM Flow Cytometry Technology Platform (FCTP). This is vital as a key flow cytometry sorter within the FCTP, a BD Influx, will be decommissioned in January 2025 as it is no longer supported by the manufacturers. Purchase of the Discover S8, in addition to expanding UoM research capabilities, will therefore be essential to support continued provision of sorting capabilities for UoM researchers.   The Discover S8 provides unique integration of imaging technology into a flow cytometer. By awarding funds to purchase a Discover S8, the BBSRC would enable UoM researchers to isolate cells; Based upon distinct cell morphology. Based on specific cell image features including protein and/or particulate cell location, diffusivity, eccentricity, and intensity. As definitive singlets and/or doublets of cells.   Being able to sort populations of cells using image-based parameters will open new avenues for research across a range of research fields, leading to breakthroughs in molecular and cellular biology.

UKRI Gateway to Research · FY 2025 · 2025-07

This project aims to develop new thermal barrier coatings (TBCs) for significantly extending the lifetime of critical high temperature components of aircraft engines under the attack of molten calcia-magnesia-alumina-silicate (CMAS) deposits. The idea is based on a novel core-shell microstructural design in which each building block of the coating will comprise a tough ceramic core and a thin, CMAS-resistant ceramic shell. Our hypothesis is that when the core-shell TBCs are under CMAS attack, the CMAS-resistant shells, which are engineered exclusively to CMAS infiltration pathways, will rapidly react with the infiltrating CMAS melt to generate crystalline products to stop CMAS penetration while the tough ceramic cores will provide high fracture toughness against crack propagation. The core-shell design fully capitalises the CMAS attack mechanisms, creates novel coating microstructural constituents and tailors the spatial distribution of the constituents for a combination of high CMAS resistance and fracture toughness, thereby overcoming the fundamental weaknesses of the state-of-the-art TBCs. The core-shell TBCs will be realised by synthesising core-shell powder and then translating the core-shell structure from powder to coating splats by thermal spray. The project will combine advanced powder processing, thermal spray, testing, characterisations and modelling to achieve the transformational core-shell design and develop fundamental understanding of the performance, failure mechanisms and structure-property relationships of the core-shell TBCs. The idea of the core-shell TBCs is transferable and will open new horizons for designing ceramic coatings for demanding environments.

UKRI Gateway to Research · FY 2025 · 2025-07

Quantitative in situ microanalysis of natural and synthetic materials underpins cutting-edge, high-impact research across the Earth and environmental sciences. Electron probe microanalysis (EPMA) is the gold standard in quantitative electron beam microanalysis. Equipped with an array of electron and X-ray detectors, EPMA measures spatially resolved major, minor and trace element compositions down to ~2 µg/g, at spatial scales down to 1 µg3 or better. EPMA supports research into natural materials that have intricate intergrowths of complex minerals with varying crystallographic orientations and structures. In most analytical sessions, multiple distinct phases are qualitatively mapped and quantitatively analysed at high spatial resolution for >10 elements in major, minor and trace concentrations. The presence and association of these elements provides critical information on the origin and history of the Earth; the evolution of life; the chemistry of the Earth's crust, oceans and atmosphere; and chemical exchanges between engineered materials and the natural environment. We propose to install a JEOL JXA-iHP200F field emission EPMA with integrated extended range soft X-ray emission spectrometer (SXES-ER) in the Department of Earth and Environmental Sciences at the University of Manchester (UoM). This asset will provide unique and transformative capability in quantitative analysis of light elements, transition metals, and heavy elements. It will enable simultaneous characterization of phase chemistry and chemical state (valence), which is challenging and expensive to achieve using existing, over-subscribed, equipment in the UK. Next-generation EPMA+SXES-ER capability will galvanize EPMA-led research aligned with UKRI NERC strategic and discovery science priorities in Frontiers of Understanding, Productive Environment and Resilient Environment, including energy and advanced materials. Examples of newly enabled research at UoM will include: - Tracking magma redox conditions, which control the formation of critical metal deposits, determine volcanic gas compositions, and affect planetary habitability; - Characterizing redox-sensitive mobility of radioisotopes, to underpin the safety case for geological storage of radioactively contaminated materials; - Determining contaminant metal speciation in mineral phases in soils and crops, to assess human exposure and develop remediation strategies. The asset will bring potential for widespread impact and economic benefit to UK research and business including critical metal resources for Net Zero; long-term storage of radioactively contaminated materials; environmental remediation; geofluids, including carbon capture and storage technology and geothermal energy. It will enhance UoM's existing research collaborations with national institutions and a wide range of industry partners, and will provide a platform to build new collaborations. The asset will be made available to external academic and industry users through a web-based application. We will facilitate capacity building by delivering advanced training in electron beam microanalysis for early career researchers, capitalizing on UoM's nationally leading scientific and technical expertise in EPMA and soft X-ray emission spectrometry. The asset will be housed in UoM's Electron Microscopy Centre alongside other internationally leading assets in analytical electron microscopy. UoM will invest £494k to cover procurement costs above the £750k requested from NERC.

UKRI Gateway to Research · FY 2025 · 2025-06

In 2018, an unexpected discovery brought to light the burial of a charioteer who lived through the Roman campaigning period and final conquest of Wales (c. 48-78 CE), catching the imagination of diverse Pembrokeshire communities. The vehicle itself is a challenging mystery: this is the ‘last’ chariot burial from northern Europe with intriguing differences to those of the earlier Iron Age, making it an internationally important discovery. Its decorated chariot-gear belongs to a period of vigorous indigenous Celtic art but other aspects hint at technical knowledge drawn from the Roman world itself. In a collaboration between the University of Manchester (UoM) and Amgueddfa Cymru-Museum Wales (AC-MW) we will use conservation-led archaeological research to analyse the cultural and historical puzzle that this vehicle poses and maximise the academic value and public benefit of this discovery. We will investigate the impact of Roman colonisation by exploring continuity and change in craft skill and technology, art and material culture, as well as beliefs and funerary rites. The project will also examine the power of the chariot as an enchanting heritage icon, with the power to appeal to different horse-loving communities, from buggy racers to carriage drivers, crossing cultural and class boundaries. We will design creative performances with local communities to shape the final story we tell and analyse how the chariot burial has become a literal and metaphorical vehicle of cynefin - the unique Welsh word that conjures how a sense of belonging can be enriched by connections with places and their past. Our four objectives are: To investigate the chariot’s materials, construction and design to examine knowledge exchange and cultural dynamics between Iron Age and Roman worlds. We will build on existing excavation and survey data, to examine this at three new scales: the vehicle, its grave and local landscape context; a regional survey of Conquest-era West Wales; and comparative survey of chariotry and chariot burial in the UK and near Continent. To explore insights from this analysis through experimental archaeology by creating two replica vehicles; one to enable the documentation and field-testing of two endangered British crafts (wagon-making and wheelwrighting) and as an ‘affective object’ to generate emotional engagements with the past, whilst the other will form an eye-catching centrepiece for exhibition. To use heritage workshops and creative arts methods to better understand how cynefin is produced through interactions with archaeological discoveries and the creative production of community stories about finds: developing heritage practice methods to deepen connections with place and care for the historic environment. To disseminate the story of the chariot and charioteers through co-produced performances, publications and exhibitions, diversifying and enriching ownership of Celtic heritage. Through academic partnership with a national museum, local arts organisations and community groups, the project will maximise the value of an unexpected and exceptional discovery. Its legacy lies in transforming these finds into national icons which speak to a wide variety of groups through themes of place, identity, resistance and resilience.

UKRI Gateway to Research · FY 2025 · 2025-06

Understanding the mechanisms of catalytic organic reactions is essential for advancing the design of new catalysts, exploring novel modes of reactivity, and developing greener, more sustainable chemical processes. Mechanistic understanding provides invaluable insights, empowering chemists to enhance chemical systems and discover new reactions in a rational and informed manner. Kinetic analysis lies at the heart of mechanistic investigations, enabling researchers to test their hypotheses directly using experimental data, allowing them to discard inconsistent proposals. However, with a few recent exceptions, current kinetic analysis pipelines rely mostly on techniques developed nearly a century ago and require the derivation of complex rate law equations involving multiple mathematical approximations that limit their applicability. Furthermore, by focusing on "kinetic orders" of reagents and catalysts, these techniques often miss out on much of the rich information present in reaction kinetic profiles. In this work, we aim to harness the power of artificial intelligence to create a more robust and comprehensive approach to kinetic analysis. Specifically, we aim to apply machine learning to the challenge of creating a model capable of processing experimental kinetic data, extracting all kinetic information, and subsequently use this information to automatically propose one or more mechanisms that are compatible with the data. We aim to develop models able to tackle various types of catalytic reactions involving one and two substrates, covering the vast majority of reactions used in academic and industrial organic chemistry laboratories. This work will lead to the development of tools that will benefit scientists in both academia and industry streamlining the development of efficient synthetic methodologies in sectors such as pharmaceuticals, agrochemicals and others that rely on the synthesis of compounds through catalytic processes.

UKRI Gateway to Research · FY 2025 · 2025-06

This grant supports IRIS Federation to deliver compute to its science activities by placing hardware at UMAN-JBCA sites.

UKRI Gateway to Research · FY 2025 · 2025-06

Two major conceptual breakthroughs have revolutionised our understanding of bacterial genome evolution during the past decade. First, genome re-sequencing of Lenski's long-term evolution experiment (LTEE) has revealed the complexity of mutational dynamics driving genome evolution, and that rates of molecular evolution are decoupled from rates of adaption through time, even for a model bacterium inhabiting the simplest of environments. Second, microbial genomics has revealed bacterial genomes to be dynamic battlefields replete with myriad defence systems (DSs) and menageries of mobile genetic elements (MGEs) that collaborate and compete with each other, whilst also spurring evolutionary innovation by driving the exchange of genetic material between lineages (horizontal gene transfer; HGT). These views of bacterial genome evolution are, however, disconnected because, by design, the LTEE used a model bacterium with a relatively simple genome depleted in MGEs and DSs compared to its counterparts in nature. Moreover, MGEs and DSs have only ever been included in short-term evolution experiments and never at levels of diversity seen in nature, meaning that their long-term impacts on bacterial genome evolution are unknown. To deliver a causal understanding of how MGEs and DSs shape long-term bacterial evolution requires that these conceptual breakthroughs be reconciled: augmenting the reductive complexity of LTEEs by integrating into this powerful approach the rich diversity of MGEs and DSs that we now know exists in nature. To achieve this, I will reboot the LTEE framework, using innovative experimental designs to directly test how MGEs and DSs shape the trajectory, tempo, and mode of long-term genome evolution and adaptation in bacteria. Discoveries from this project will transform our causal understanding of long-term bacterial evolution, enhancing our ability to predict the behaviour of natural systems, and forging an eco-evolutionary view of bacterial genomes.

UKRI Gateway to Research · FY 2025 · 2025-05

Cardiovascular disease, including damage to heart muscle, kills more people worldwide than any other illness. The cardiovascular research community aims to solve this by tackling it from multiple angles. Human pluripotent stem cell (hPSC) technology promises to underpin many translational approaches including cardiac regenerative medicine (cell therapy), heart disease modelling including congenital heart disease (CHD), and drug and gene therapy screening platforms. However, a major roadblock holding back medical advances is the uncontrolled and heterogeneous differentiation of hPSCs, which is commonly observed in practice and is partly due to our poor understanding of the gene regulatory mechanisms coordinating development. The progenitors of the heart are known to acquire their identity and lineage assignment early in embryogenesis very soon after the mesoderm starts to form. This research will focus on accurately controlling this early step of hPSC differentiation by understanding the function of the transcription factor HAND1 and its relationship with other transcription factors expressed in mesoderm, particularly the 'cardiac master regulator' MESP1. Using CRISPR-Cas9 screening technology we will also investigate the gene regulatory elements (enhancers and silencers) of HAND1 and discover how its expression is turned on and tuned, obtaining practical knowledge for its better control, and revealing fundamental mechanisms of mesoderm fate determination. Our increasingly detailed molecular profiling of cardiac cell development in our in vitro stem cell model presents a particular opportunity to gain insight on the genetic causes of CHD. With a growing number of DNA variants clinically associated with CHD, the genotype-phenotype relationship is currently beyond our understanding in most cases. Again, drawing on CRISPR-Cas9 screening technology, the final objective of this research is to test how genes implicated in CHD may affect the specification, self-renewal, or differentiation of cardiac progenitors. This information will add additional layers of knowledge to our understanding of the mechanisms behind the cardiac lineage fate map. The testing platform will also be of clinical importance for supporting the genetic diagnosis of CHD and delivering personalised medicine. Combining its overlapping components, in sum this work will deliver a step change in stem cell research for applications in cardiology. It will uncover how the different lineages of cardiac progenitors are programmed and how seemingly linear gradients in transcription factor expression can be transformed into discrete and robust fate choices. It will uncover en masse how mutations associated with CHD impact the cardiac cell development process. These advances will catalyse a range of translational applications in cardiac regenerative medicine and the modelling of CHD to help tackle the global burden of heart disease.

UKRI Gateway to Research · FY 2025 · 2025-05

Perovskite solar cells (PSCs) have emerged as the next-generation photovoltaic (PV) technology that offers high performance and low projected manufacturing costs. However, the current perovskite/charge-transport-layer (CTL) contacts lack the required long-term structural and performance stability, which hinders the market entry of perovskite-based PVs. The instability of perovskite/contact interfaces is a multifaceted challenge that requires a holistic solution to the interfacial defect, charge transfer, chemical stability, and delamination problems. To overcome this challenge, it is imperative to design novel charge-selective molecules that can simultaneously passivate perovskite/contact interface defects, facilitate charge transport, form a stable barrier layer, and preserve the integrity of the contact stack. Therefore, this proposal aims to synthesize a new class of charge-selective molecules and use them to design highly stable perovskite/CTL contacts that will enable the fabrication of high-efficiency and long-term stable PSCs. Unlike existing CTLs, the newly developed charge-selective molecules will be perovskite-specific and incorporate functional linker units, targeting to address all perovskite/contact interface problems simultaneously. Different from the existing literature studies, this project will follow not a specific but a complete set of the International Summit on Organic Photovoltaic Stability protocols to reveal the 'true' reliability of perovskite/contact interfaces. The holistic approach of this project, coupled with extensive characterizations, will generate new knowledge to address the long-lasting stability issue of PSCs, thereby enabling the commercialization of this promising technology. Overall, the advanced device concepts that will be developed could pave the way to the next generation of PV technologies beyond 2030.