University of Cambridge

UKRI Gateway to Research · FY 2025 · 2025-11

The past decade has seen an exponential increase in AI engagement across scientific disciplines, notably in the life sciences, where it is used for complex, data-intensive tasks including the identification of disease genes, the prediction of protein folding and protein-drug interactions and the design of molecular tools. Originally a niche field of computer science, AI has diffused out into the wider research landscape and is reshaping the way in which science is conducted. For AI to have a positive impact on science and society, development of machine intelligence must be informed by cross-disciplinary insights from different research fields, as well as by other facets of human knowledge and experience: AI that is both led by humans, and that can serve real-world science needs. This project aims to explore the roles of humans in AI for life sciences research, defining how AI model training and development is guided by researchers, how humans interpret and validate knowledge generated by computers, and how computer scientists interact with other scientific researchers to transfer knowledge between different disciplines. Gathering evidence and developing understanding of these issues is critical both to the design of new AI techniques that serve the needs of science, and to the establishment of trust in AI by researchers and the general public.   AI methodology is commonly underpinned by machine learning algorithms that are trained on datasets. In life sciences research, these can include both quantitative data, DNA sequences, RNA and protein expression patterns, images and text. AI can be used to identify patterns in unlabelled data, termed ‘unsupervised’ learning, or be trained using human- or machine-labelled datasets, termed ‘supervised’ learning. AI can also be trained using reinforcement methods, in which a machine makes initially random decisions that are then corrected by humans to progressively improve task performance. Interactions between humans and machine learning algorithms enable the transfer of human knowledge to computer models, not only hard data, but the fine nuances of human experience. For AI to be both demonstrably free from bias and trustworthy, its knowledge outputs must also be 'explainable' to the human researcher: the route by which they are generated must be decipherable and transparent. Maximising the potential of AI to tackle complex research questions is critically dependent on cross-disciplinary collaboration between computer scientists, who typically build AI models, and other scientific researchers, who can provide domain-specific expertise to guide their training and harness their outputs to accelerate scientific discovery.   This project will carry out quantitative reviews of relevant academic and grey literature, and in-person and questionnaire-based interviews with life science researchers who employ AI techniques in their work. I aim to answer the following questions: In which ways do human researchers interact with machine learning algorithms to train AI models? What steps are taken to ensure that the outputs of AI models are explainable? What motivates life sciences to make choices about AI methodology and how do they work together with computer scientists?  By answering these questions, I will generate the first comprehensive analysis of the ways in which humans and computer AI models co-create knowledge for life sciences research. These findings can both help shape the evolution of useful and trustworthy human-inspired AI to address the research questions of the future, and inform the evaluation of transparency and explainability required for AI assurance regulatory frameworks.

UKRI Gateway to Research · FY 2025 · 2025-11

Schizophrenia is a devastating psychiatric disorder for which there is no cure.  Clinically, it is associated with three types of symptoms: psychotic symptoms that are fairly well treated with antipsychotic drugs, and alterations in emotional and cognitive processes that are harder to treat, and profoundly impact quality of life. Brain imaging studies in patients with schizophrenia and rodent models of the disorder have identified problems in the connectivity between regions of the brain called the anterior hippocampus (aHipp), orbitofrontal cortex (OFC) and dorsolateral prefrontal cortex (dlPFC) that contribute to these symptoms. Unfortunately, differences in the structure and complexity of rodent and human brains mean that we lack a fundamental understanding of how these alterations in brain connectivity contribute to these cognitive impairments. This limits our insight into the brain mechanisms underlying these important symptoms and restricts our ability to target existing treatments appropriately, refine treatment strategies, and develop novel, more effective treatments. To address this challenge, we have developed and validated a primate-based approach for the study of schizophrenia symptoms - marmoset aHipp perineuronal net degradation.  Crucially, the use of a marmoset, a small New World monkey with a brain structure closer to humans, permits the study of aHipp-OFC/dlPFC connectivity and its role in schizophrenia symptoms. We now aim to capitalize on this approach to identify the neurochemical and anatomical basis of defined cognitive abilities known to be disrupted in schizophrenia. We will apply a repertoire of techniques that are rare in primates and include direct pharmacological manipulations of the brain, magnetic resonance and positron emission tomographic brain imaging (MRI and PET), and sophisticated, unrestrained behavioural testing using both well-validated and novel tasks. Specifically, we will: Characterize the functional impact of aHipp degradation on different aspects of OFC- and dlPFC-dependent schizophrenia-relevant cognition (goal-directed learning processes, working memory and aberrant salience). Utilize the changes in brain chemicals that we previously identified in the OFC and dlPFC to target these cognitive abilities pharmacologically, and ameliorate any cognitive impairments with both receptor specific and putative antipsychotic compounds. Extend this approach into adolescent marmosets to characterize the impact of compromised aHipp-OFC/dlPFC connectivity during development on their cognitive abilities in adulthood. Consequently, this proposal will enhance our understanding of the brain mechanisms underlying these debilitating symptoms, and reveal how abnormal development of these brain connections contribute to cognitive dysfunction. In doing so, this proposal also aims to provide insight into strategies for the prevention and symptom-specific (rather than disorder-specific) targeting of potential treatments for use by researchers, and ultimately to benefit patients.

UKRI Gateway to Research · FY 2025 · 2025-11

Disease prioritisation frameworks inform national approaches to health and disease. They are policy tools to support lower- and middle-income countries (LMICs) in ranking diseases in order of importance. But outcomes generally over-reflect Global North agendas, with overwhelming focus directed towards diseases that have potential to pose a pandemic, biosecurity, or global trade risk. This emphasis on threats has meant that important common diseases are often ignored, and what matters to the wellbeing and health of marginalised communities is frequently disregarded in the prioritisation of resources. This Fellowship aims to bridge the gap between geopolitical concerns and the priorities of marginalised communities in LMICs who are disproportionately affected by common, “endemic” human and livestock diseases. Through social science analysis and engagement focused on a setting in Kenya, it seeks to bring local understandings of the causes and consequence of disease into national policy and disease control approaches, generating tools and lessons for broader application. The Fellowship will support me in consolidating my PhD which addressed issues of equity and inclusion in the prioritisation, surveillance, and burden of human and livestock diseases, including zoonoses – diseases that transmit from animals to people. Through ethnographic and participatory research with Kenyan Maasai - pastoral communities where cattle are embedded in sociocultural domains, power, and livelihoods - I explored how lived experiences, social inequities and histories, and the centrality of cattle, collectively shape priorities, conceptualisations of risk, and indigenous (Maa) language disease ontologies. As a form of knowledge management, ontologies represent a shared understanding and philosophy, supported by an agreed vocabulary. The Fellowship will enable me to conduct minimal additional participatory validation activities with original study communities to enhance rigour and validity of an indigenous language cattle disease ontology framework developed during my PhD. Such a framework will offer avenues to integrate local priorities in disease policies, including surveillance and prioritisation, providing an innovative approach to facilitate knowledge co-creation between communities, scientists, and policymakers. Publications arising from this work will complement my critical analysis of the primary zoonotic diseases prioritisation tool which found significant methodological gaps. The tool, adopted by policymakers in over two thirds of African nations, including Kenya, lacks sufficient frameworks for ensuring transparency. This impedes capacity to validate and justify outcomes, raising alarming questions of equity and inclusion. My analysis further interrogated top-down approaches to disease surveillance and control in remote rural settings where community members are often treated as passive data providers, recruited to report specific events to authorities. Surveillance is a key priority for economic and political agendas, and has potential to generate critical data for disease prioritisation. But such instrumentalist approaches to involving communities disregards the value of their knowledge; it positions people as tools, and ignores the interests and needs of those living with disease. One of several planned publications, my manuscript will offer recommendations, informed by decision theory and anthropology, to improve prioritisation and ensure transparent inclusion of local priorities in national policies. All findings will be shared in accessible formats with study communities, ensuring transparency and collective benefit. Abstracts will also be submitted to key conferences, and findings will be presented and shared with national and regional stakeholders in Kenya. Overall, this Fellowship will offer pivotal career development opportunities, enabling me to contribute to academia and society, while building my network and applying for further funding.

UKRI Gateway to Research · FY 2025 · 2025-11

Evolution by natural selection can occur rapidly and over short timescales, but the degree to which such short-term evolution is predictable and repeatable between populations and species remains unclear. Recent analytical advances offer the ability to address hypotheses over recent timescales from genomic data, but tracing the repeatability of selection will also require fine scale spatial and temporal sampling across multiple species. Here we explore signatures of demography and selection in a guild of species critical to global food security: the lepidopteran soybean pests of Brazil. Taking advantage of an established international collaboration with Brazilian scientists, we will study a unique collection of eight soybean pest species collected from 800 sites across Brazil over six years. The project has the following goals: Reference genome assembly for a pest guild: First, we will build reference genomes for five species, such that high quality chromosome level reference genomes are available for the entire guild of pests (three species are already sequenced). Population genomics of expanding crop pests: Next, using whole genome re-sequencing we will study the recent population history of the 8 species, to explore signatures of variation in the genome across an entire guild of species found in the same agricultural environments. These species have contrasting recent histories of expansion and contraction in response to changes in control measures, offering a unique opportunity to compare census and genetic estimates of population size across species. We will then apply novel cutting edge methods developed for humans to explore movement across the landscape, identifying connectivity and barriers. Identify the genetic basis for recent selection: We will test how often the same regions of the genome are implicated in climate and crop adaptation across species subjected to the same selection pressures. We will conduct genome wide association studies to identify genetic variants associated with climatic variables, and with transgenic crop type. This will be complimented by genome-wide selection scans, drawing a link between genotype and selection pressure. We will also take advantage of our temporal sampling to look for consistent changes in allele frequency through time to test whether allele frequency changes are repeatable across geographic space and between species. Develop an amplicon panel for cost effective genomic monitoring of pest species and insecticide resistance: Finally, we will use the genomic data acquired here to develop an amplicon panel for rapid monitoring of lepidopteran pests and their resistance to control measures. This will allow rapid acquisition of genome-scale information on pest outbreaks as they occur, greatly facilitating pest monitoring. It will also allow provide detailed temporal data for much larger sample sizes, to further test our hypotheses regarding the action of selection. Training workshop: We will run a genomics training workshop in the UK for Brazilian and UK postgraduate students. The project will explore fundamental questions about the repeatability of evolution over short timescales, as well as generating detailed knowledge of pest movement and demography, identifying genes associated with Bt resistance, and developing a tool for rapid pest monitoring. The genomic resources generated will serve as valuable tools for future research in pest biology and resistance. This project is highly relevant to BBSRC’s long-term research and innovation priorities, particularly in sustainable agriculture and crop protection and fits the BBSRC research priority “Understanding the rules of life” and strategic impact priority “Sustainable agriculture and food”.

UKRI Gateway to Research · FY 2025 · 2025-11

This project will produce the first comprehensive edition and analysis of the principal corpus of primary documentary evidence for the history of Wales during the early medieval period (c. 600–1100). Approximately 180 documents survive from Wales in this period, deriving from four ecclesiastical archives located in different parts of Wales: Llandeilo Fawr in Carmarthenshire, Llancarfan and Llandaf in the south-east, and Clynnog Fawr in Gwynedd. They preserve precious evidence for early political and social organisation in Wales, a place not otherwise well represented in primary sources, and collectively form the single most substantial source for the earliest stage of the Welsh language, known as ‘Old Welsh’. Although the bare texts of these documents have been published before, chiefly in nineteenth-century editions, they all still lack reliable and scholarly modern editions that could form a secure basis for using them. One aim of this project is thus to create the first comprehensive academic edition of the early Welsh charters dating to the period 600–1100. This would provide a valuable and enduring resource for scholars interested in a variety of topics, including the history of Wales, the development of the Welsh language, Welsh place-names and topography, and the development of documentary culture in medieval Britain. A remarkable feature of these documents, which distinguishes them from most similar documents across Europe outside England, is that they contain approximately 118 detailed descriptions of the boundaries pertaining to the estates that are granted in them. Most of these are written in Old Welsh. Altogether, this forms the earliest detailed written record of the Welsh landscape in relation to its usage and its residents. It can be highly challenging to relate these boundary descriptions to the modern map: place-names can change, some regions of Wales have subsequently been Anglicised, and even the physical morphology of the landscape has shifted over time. Nonetheless, it is possible to make substantial progress in our understanding of these records through a focused programme of research. Hitherto, most early boundary descriptions have been compared only with published sources, such as nineteenth-century OS maps. By contrast, little use has been made of estate and enclosure maps from earlier periods, despite the fact that these maps preserve a greater proportion of the early local toponomy than the later published sources. It is the intention of this project to make a systematic comparison of the early boundary descriptions with surviving estate and enclosure maps, alongside other estate records such as the sixteenth-century records of the Court of Augmentations, since this will substantially enhance our understanding of the boundary descriptions and generate new knowledge about the historical development of the landscape over time. The facilitation of access to this record would be of wide interest and benefit others such as archaeologists, the heritage sector, and local Welsh communities. A second key output of this project will therefore be a freely accessible online historical atlas, where the new research into these boundary descriptions can be approached by means of a layered 3D digital map.

UKRI Gateway to Research · FY 2025 · 2025-11

Context The discovery of high-temperature superconducting magnets has allowed the design for fusion devices to shrink considerably. Whilst this will result in large economic benefits, operating components in such a proximity to the reactor core only pushes them closer to the point of failure: containing a Sun in a box is no mean feat. “Saving Icarus” aims to increase the operating temperature of reduced-activation fusion steel using additive manufacture (AM) to design and engineer a microstructure that is stable at elevated temperatures. The connection enabled by this project This collaborative project brings together experts on AM and alloy design at the University of Cambridge (UoC) with the Materials and Fusion Technology divisions at the UKAEA. The alloy design will revolve around a spatially engineered microstructure concept, which is pioneered by the group at UoC and is enabled by AM. The goal of the project is twofold. First it will demonstrate the viability of using AM technology to improve performance and lower the cost of fusion applications. Second, it will showcase the benefits brought about by materials with spatially varying microstructure, which may have implications for different engineering problems. The challenge addressed Current reduced-activation ferritic-martensitic (RAFM) steel alloys proposed for use in plasma-facing components in the reactor core—such as breeder blankets—cannot operate at temperatures exceeding 550°C. Beyond this baseline, creep, thermal cycling, and radiation damage accumulation will cause failure and limit the lifetime of the reactor significantly. The UKAEA has identified a class of high-strength RAFM steels with finely dispersed nano-precipitates as a possible material solution to raise the operating temperature to 650°C. However, these materials are difficult to manufacture and assemble into large components. As a result, making breeder blankets out of these materials is costly and would require multiple weld joins, which irremediably compromise the alloy’s unique microstructure and introduce possible failure points. Aims and objectives This project will address the above challenges by enabling net-shape manufacturing of these advanced steels with spatially controlled microstructure using AM technology. The part design consolidation offered by AM will allow reducing the number of joints required to make large scale parts, lowering the production cost and ensuring safer operations. Moreover, site-specific ‘tuning’ of the alloy microstructure will be used to make parts with graded precipitate density; high in the hot, plasma-facing regions and absent in colder ones, which may be safely welded to other subcomponents. The objectives of this project are thus two: 1) demonstrating the printability of these high strength alloys with tuneable density of precipitates and 2) producing a demonstrator breeder blanket subcomponent with optimized microstructural gradient. Potential applications and benefits The adoption of advanced, near-net shape manufacturing technologies is a crucial step to realising commercially-viable power generating nuclear fusion reactor designs. As such, this manufacturing development will be of interest to a range of public and private organisations which are currently engaged in these designs. This represents an exciting opportunity for the UK to lead the energy revolution. As an indication of scale, the Fusion Industry Association reported that in 2023 the fusion sector global invested $1.4B, of which private sector operators raised $271M. Translation projects, such as Saving Icarus, are ideally positioned to feed into and leverage off this growing industrial opportunity.

UKRI Gateway to Research · FY 2025 · 2025-11

Building on my previous research and engagement with education stakeholders, my postdoctoral project focuses on strengthening how Nigeria develops and implements its language of instruction (LOI) policies in primary schools. With over 500 languages spoken across the country, many children are taught in languages they don’t understand, undermining their learning from the very start. While Nigeria’s national policy encourages teaching in mother tongues during the early years of schooling, implementation remains inconsistent and poorly supported in many areas. This project aims to bridge that gap by combining data analysis with practical policy engagement. A core part of the project involves publishing one remaining paper from my PhD. The first paper explores how school type - public versus private - shapes student learning outcomes in Nigeria. Alongside the research, I will lead a training programme for data analysts and education officers at Nigeria’s Federal Ministry of Education. This training will build their capacity to use national datasets to identify trends in areas like student performance, teacher qualifications, and resource distribution. The aim is to support Nigeria’s efforts to strengthen its Education Management Information System (EMIS) and make better use of data in shaping and monitoring LOI policies. Another key strand of the project is the development of a practical toolkit to guide the implementation of language policies in schools. I produced a draft version of this toolkit during a previous Knowledge Exchange project, drawing on insights from my PhD and consultations with education stakeholders. During the fellowship, I will revise and expand the toolkit based on new findings from my updated research. I will also work closely with policymakers, teachers, and officials to test and improve the toolkit through structured pilot sessions, ensuring it responds to the realities they face. Finally, I will partner with government agencies, NGOs, and education networks to share the final version and support its uptake in policy and practice. This project addresses a key challenge in education systems across multilingual countries: how to design and implement language policies that genuinely support children’s learning. By producing new evidence, offering practical tools, and working directly with education stakeholders, I hope to contribute to more effective and inclusive education policy in Nigeria. The fellowship will also allow me to grow as a researcher and practitioner, deepening my experience in policy engagement, capacity building, and research communication, and helping ensure that evidence plays a central role in education reform efforts.

UKRI Gateway to Research · FY 2025 · 2025-10

Electricity demand in the UK varies from a low of 1 TWh/day to a peak of up to 4 TWh/day in the winter. The difference is currently met mostly by natural gas supplies, and represents about 100 TWh/year. A zero-carbon scenario requires that the balance comes from either large installed capacity or storage.  This cannot be met by batteries, as the largest facilities are smaller than 4 GWh, so other means of storage are necessary. Hydrogen is considered a key energy storage vector for seasonal applications in a fully renewable energy system. Key to the successful utilisation of hydrogen as a seasonal energy vector are high efficiencies in the round-trip generation via electrolysis (typ. 60-70%) and equally efficient conversion back into electricity. Importantly, it should also generate zero NOx emissions, which are produced in combustion processes with air. The use of pure hydrogen and oxygen instead of air would produce very high temperatures incompatible with normal materials. Liquid water offers the ideal combination of high heat of vaporisation to lower the temperature, high availability and zero environmental impact. We propose to investigate a closed-loop, zero-emissions (CloZe) energy conversion system based on Hydrogen-Oxygen combustion diluted by Water injection as Liquid (HOWL). The liquid is used first for cooling the combustor walls, then sprayed and vaporised as a diluent. The generated steam is expanded to ambient pressures and condensed to ambient temperatures as in a conventional steam cycle, either in one stage or via reheat. The remaining water vapour is condensed, and brought back to the system via a liquid pump. The expected power cycle efficiencies are of the order of 50-70% depending primarily on the combustor pressure. The price to be paid is the compression and storage of both hydrogen and oxygen, consuming a few percent of the total energy available. The challenges in the HOWL cycle are associated with the effective design of water-based evaporative cooling systems and spray delivery leading to complete combustion and uniform temperatures,  primarily to ensure the safe and efficient operation at stoichiometric conditions at maximum performance. The work in this project will develop the tools for design, validation and testing of the liquid water injection, mixing, and cooling in a HOWL combustor,  allowing de-risking of the detailed design and deployment of such systems in the future. Advanced laser based imaging for measuring instantaneous local species and temperatures will be used to acquire scalar, velocity and spray data. High performance numerical methods will be deployed to validate and interpret the behaviour of these systems at pressure, creating models for use in the design of new generation high efficiency, zero-emissions closed-cycle energy production systems.

UKRI Gateway to Research · FY 2025 · 2025-10

This proposal puts forward a combined experimental and computational study to investigate and precisely assess the wall similarity hypothesis for a broad class of non-equilibrium rough-wall turbulent boundary layers. This issue is crucial to the application of RANS CFD to a vast array of practically relevant flows and to the prediction of separation, drag, performance, flow-induced vibration and noise. The work will combine state of the art experimental capabilities and experience at Virginia Tech, with leading edge computational expertise at the University of Cambridge. In addition to conclusively resolving key scientific issues and bringing new insight into the physics involved, the work will engage and train researchers at the postdoctoral, PhD, undergraduate and high-school levels, enable cross-cultural and interdisciplinary international exchanges, and provide unique research experiences for hundreds of undergraduate engineers.

UKRI Gateway to Research · FY 2025 · 2025-09

Monkeypox virus (MPXV) clade 2b has caused a global outbreak since 2022, affecting 88,000 people across >100 countries. A further outbreak of MPXV clade 1b started in the Democratic Republic of Congo in September 2023, causing ~20,000 cases and 1,300 deaths so far. MPXV causes a smallpox-like illness, and can cause life-threatening infection in immunocompromised individuals, children and pregnant women. Children under the age of 5 have accounted for 62% of the deaths from the most recent outbreak. MPXV was recently declared a public health emergency of international concern by the WHO, the category used in the past for Ebola outbreaks and COVID-19. MPXV has emerged and re-emerged over five decades yet basic aspects of its biology still remain to be discovered. Furthermore, there are only two antiviral drugs, with evidence already for drug resistance. New treatments based on a comprehensive understanding of how the virus interacts with the host are vital.   One of the first lines of defence against MPXV and other viruses are ‘cell death pathways’, by which infected cells die to prevent viral spread. To counteract this defence and promote their successful replication, some viruses including MPXV inhibit these cellular pathways.   We aim to understand how MPXV prevents cell death. We have made the crucial discovery that a viral protein called MPXV4 inhibits a key cell death pathway called pyroptosis. Furthermore, our initial data suggests the existence of other, as yet undiscovered MPXV inhibitors of cell death. Critically, a detailed understanding of how MPXV4 and other death inhibitors function will enable us to develop new antiviral treatments that restore cell death as a vital defence against infection.   We will (1) identify and characterise new ways MPXV inhibits cell death (2) determine how MPXV targets cell death pathway components for destruction; (3) gain a structural understanding of how each viral death inhibitor interacts with its cellular protein target. To achieve these aims, we will study skin cells and immune sensing cells, which both play vital yet distinct roles in MPXV infection.   Understanding how MPXV and other viruses subvert cell death pathways will eventually allow us to develop vital new treatments to prevent diseases caused by MPXV. Crucially, this knowledge will also improve our understanding of cell death in general, which will benefit multiple lines of research including into sepsis, neurodegenerative disease and cancer.

UKRI Gateway to Research · FY 2025 · 2025-09

Huntington's disease is caused by a genetically expanded CAG repeat encoding a poly-glutamine tract in exon 1 of the Huntington protein (HTT). The disease is dominantly inherited and is characterised histopathologically by aggregation of mutant HTT. There remains no cure and lingering uncertainty as to the molecular features that drive pathology. New methods are urgently required to enable dissection of the molecular pathogenesis and provide new routes to therapeutics. We have demonstrated the existence of intracellular innate immune pathways present in all cell types that can be leveraged for the degradation of intracellular protein aggregates. Driven by the intracellular antibody receptor and E3 ligase TRIM21, these pathways can destroy large aggregates of the neuronal protein Tau over the course of a few hours. As activation of TRIM21 is driven by clustering of its RING E3 ligase domain, this activity can be leveraged to provide selectivity for aggregates, leaving soluble monomeric protein untouched. Based on these findings in Tau, we believe there is an opportunity to develop HTT expansion-selective degraders (ie that specifically degrade proteins encoded by the mutant expanded allele, leaving the wild type proteins alone) as well as aggregate-selective selective degraders. Supported by data showing that TRIM21 is in principle capable of performing both these degradation modalities, we will develop a suite of genetically-encoded HTT-directed degraders. By targeting different epitopes on the HTT protein that are predicted to elicit TRIM21 activation when either expanded or aggregated, we expect to define a panel of degraders with diverse degradation characteristics. The panel will be extensively characterised in cellular models of HTT protein expansion and aggregation. As selective protein-level knockdown tools, the degraders will be exploited in a range of cellular models including iPSC derived neurons to assess the extent to which expansion and aggregation contribute to toxicity. Finally, we will test the ability of our degraders to elicit selective protein knockdown in a mouse model of Huntington's disease. The tools and data generated will provide new methods for the selective depletion of HTT protein and its aggregates. These are expected to be of high value to the research community in helping address the fundamental nature of which protein species contribute to disease progression and thus should be targeted therapeutically. The work will leave the team in an excellent position to extend the studies to address further research questions and assess the suitability of degraders for an AAV gene therapy approach.

UKRI Gateway to Research · FY 2025 · 2025-09

Most animal tissues are composed of sheets of epithelial cells that are polarised along their apical-basal axes by conserved polarity factors that define their apical, junctional and lateral domains. Coordinated cell shape changes in epithelial sheets drive morphogenesis to form more complex structures. For example, apical constriction bends epithelial sheets to drive to tube formation. Epithelial morphogenesis therefore requires changes to the relative sizes of the cells' apical, lateral and basal domains, but how polarity factors regulate and are regulated by these changes is unknown. We discovered that the substrates of the key effector of apical domain identity, atypical protein kinase C (aPKC) differ 500-fold in their sensitivity to aPKC inhibition. Thus, like the growth regulator TORC1 and the cell cycle kinase Cdk1, aPKC functions as a rheostat that phosphorylates fewer substrates as its activity decreases, a property that is evolutionary conserved. We found that a small reduction in aPKC activity blocks only the phosphorylation of its lowest affinity substrate Yurt (EPB41L5/Lulu1 in mammals), leading to apical Yurt localisation and apical constriction, the first example of a morphogenetic process driven by a polarity protein. Mild aPKC inhibition also induces endocytosis of the apical determinant Crumbs, which is an early step in epithelial to mesenchymal transitions (EMT).  Thus, aPKC modulation provides an attractive mechanism to link the polarity system to morphogenesis. This proposal sets out to determine how aPKC regulates Yurt and Crumbs and the role of this pathway in Drosophila development. 1) We will  investigate the mechanism of Yurt-mediated apical constriction, as identifying the components of this novel myosin activation pathway will provide clues about where it functions. 2) We will identify the aPKC substrate that regulates Crumbs endocytosis and map the aPKC phosphorylation sites in it and Yurt. 3) The most rigorous test of aPKC's function as a rheostat is to turn its low affinity substrates into high affinity substrates, so they are still phosphorylated when aPKC is less active. We will therefore change the relevant sites in Yurt  into high affinity sites and examine the phenotypes. As an alternative strategy, we will prevent the apical recruitment of Yurt by Crumbs by mutating the Yurt-binding site. We will then use these tools test the following hypotheses: i) This pathway could function as a homeostatic mechanism to maintain apical domain size in response to stretching, as stretching should dilute apical aPKC activity and induce constriction. We will test this in collaboration with Yanlan Mao (UCL) by stretching wing imaginal discs and examining Yurt localisation. ii) aPKC activity could be developmentally down-regulated to promote apical constriction. We will test this in the salivary placode, which is an excellent candidate for such a mechanism because it has lower levels of aPKC along its external periphery, where a contractile myosin cable forms. iii) Cells undergoing EMT apically constrict and endocytose Crumbs, both hallmarks of mildly reduced aPKC activity. We will test in delaminating neuroblasts whether EMT is coordinated by reducing aPKC activity. This project investigates a new, conserved pathway that controls epithelial morphogenesis and links the polarity system to cell shape control. It will therefore inform research in many areas of invertebrate and vertebrate development. It may also be relevant to medical research, since EMT contributes to cancer metastasis. It  falls within the BBSRC's strategic objective of "understanding the fundamental rules of life".

UKRI Gateway to Research · FY 2025 · 2025-09

Autistic people (diagnosed with autism spectrum disorder according to diagnostic criteria) number at least 80 million worldwide.  In the last decade research has clearly reported that autistic people are more likely to think about, attempt and die by suicide than people who are not autistic.  In 2023, the UK Government identified autistic people as a priority group for suicide prevention for the first time.  Population data in the UK reports that autistic children and young people are twice as likely to die by suicide than their non-autistic peers, however, most research to date has been undertaken with autistic adults.  One limiting factor in designing interventions is that the way that we think about, conceptualise and understand suicide in non-autistic people is not necessarily meaningful for autistic people. Suicide models designed in non-autistic people are less accurate to describe the experiences of autistic people.  Important factors driving suicide in autistic young people remain unidentified, which means we have a weak evidence base to design interventions and support. This programme of work will start with the lived experience of autistic young people in recovery from suicidal thoughts and feelings.  Using a co-design approach will build high level research skills, practitioner and international networks and prepare for research that can create a theory of suicide in autistic children and young people that is grounded in clinical practice.  Such a theory can ensure that, for the first time, the way that we identify those most at risk, formulate support and design suicide prevention interventions can be meaningful and effective for autistic people.  Outputs of this fellowship prepare the ground for high impact research applying cutting edge statistical and qualitative methods.  These include publications in the highest ranked journals, such as Nature Mental Health, a multi-disciplinary Special Interest Group at the International Association for Suicide Prevention and a prestigious symposium presentation at European Symposium on Suicide and Suicidal Behaviour on novel approaches to suicide prevention in autistic children and young people.  In summary, this programme lays the groundwork for future translational research that can make a real difference to autistic children and young people who experience these difficulties and those who support them.

UKRI Gateway to Research · FY 2025 · 2025-09

In Newtonian physics, matter produces gravity. In General Relativity, gravity is replaced by curvature: Einstein’s equations tell us that matter on a spacetime causes it to curve. Surprisingly, they also tell us that gravitational energy itself can interact to form nontrivially curved geometries, even in the absence of any matter! One class of examples are black holes, strongly curved spacetimes characterized by having a region which is causally disconnected from its complement. The strong curvature, or “gravitational pull,” associated to black holes suggests that we are fated to end up in one. In mathematics, this expectation goes by the name of final state conjecture: slightly more precisely, it asserts that (the exterior regions of) vacuum stationary black holes are the endstate of a generic initial configuration for Einstein’s equations. All vacuum stationary black holes are conjecturally members of a single two-parameter family, the Kerr family (a,M) with |a|=M. Therefore, a basic test of the final state conjecture is to understand if it holds for initial configurations which are already close to Kerr values. In other words, are Kerr black holes stable? This question is fundamentally interdisciplinary in nature: it lies at the intersection of Physics (it concerns a physical theory), Geometry (the object of study is spacetime), and Analysis (stability is best understood in the language of differential equations). In this project, mainly relying on techniques from Geometry and Mathematical Analysis developed in the last 3 decades, we seek to understand the stability properties of Kerr black holes under the linearization of the Einstein vacuum equations, up to and including the extremal case |a|=M. In the subextremal case |a|

UKRI Gateway to Research · FY 2025 · 2025-09

Despite being the epitome of strength, the solid rocks below Earth’s surface can flow surprisingly rapidly over human timescales, impacting processes of societal relevance. This project aims to deliver new equations describing this flow based on the underlying processes operating in the rocks. Major earthquakes and the melting of ice sheets cause deflections of Earth’s surface that are facilitated by viscous flow of the hot rocks below. This deformation creates important feedbacks. During the seismic cycle, earthquakes induce viscous flow of rocks beneath the fault zone that impacts the spatial and temporal distribution of future earthquakes. During the glacial cycle, viscous flow of rocks beneath melting ice sheets causes ground uplift that impacts sea-level change. Therefore, modelling these systems requires knowledge of the viscosity of rocks in Earth’s lower crust and upper mantle. During the first phase of this project, experimental data and observations of the microstructures of deformed rocks provided the basis for a new framework of equations describing how the viscosity of rocks evolves as they flow. However, this work also highlighted important knowledge gaps regarding the fundamental microphysics of flow and how key processes should be mathematically described. At a time when populations exposed to seismic risk are rapidly expanding and when the modelling of ice-sheet dynamics is of unprecedented importance, it is critical to delve deeper into the microscopic processes of viscosity evolution in the rocks that underpin these systems. Deciphering the microphysical processes that control the viscosity evolution of rocks requires an ambitious multidisciplinary approach. Each element of the research will be centred on the novel adaptation of techniques from the forefront of the materials sciences to analyse key geological minerals. Experiments will be conducted at temperatures up to 1600 degrees Celsius and will induce viscosity evolution by imposing instantaneous changes in the applied forces, analogous to those imposed by earthquakes. At the same time, we will monitor sound waves emitted by defects in the crystals to characterise the fundamentals of their behaviour during flow. Using a new approach pioneered in the first phase of the project, a subset of the experiments will be performed inside a scanning electron microscope allowing the samples to be directly imaged during the tests. The microstructures of the samples will be analysed using state-of-the-art microscopy techniques, pioneered by our group, to measure distortions of the crystal lattices and the forces trapped within them. The combined mechanical data and microstructural observations will provide the new insights necessary to determine what controls key effects, such as the rate of viscosity evolution. Using the refined equations describing viscosity evolution, we will begin to explore the impacts of our work for the behaviour of fault zones over the earthquake cycle and rebound of underlying rocks as ice sheets melt. To build understanding of how the relevant materials and systems behave, we will take a multilevel modelling approach. First, we will analyse simplified scenarios designed to capture the key aspects of the flow of deep, hot rocks in the aftermath of major earthquakes or melting ice sheets to gain intuition of the most important effects. Second, we will integrate our new equations into three-dimensional models of Earth’s crust and mantle to simulate specific earthquakes and melting ice sheets to understand how these systems are likely to behave into the future.

UKRI Gateway to Research · FY 2025 · 2025-09

The Cambridge High Energy Physics Group focuses its research activities on experiments at high-energy accelerators, currently the Large Hadron Collider and the ATLAS and LHCb experiments at CERN, the neutrino experiment MicroBooNE, and the long-baseline neutrino experiment DUNE at Fermilab, and future collider facilities such as the FCC. The goal is to understand the fundamental particles of nature and their interactions, in particular, to discover physics beyond our current understanding, to understand why the Universe is made only of matter and not antimatter and to reveal the identity of dark matter. The Group is also central to the multi-disciplinary Quantum Technologies for Fundamental Physics projects, AION and MAGIS, which use novel atom interferometry to detect and identify sources of dark matter and gravitational waves in the Universe. This grant will enable the group to fully exploit the physics of the LHC, to deliver our commitments to the current upgrades of the ATLAS and LHCb experiments, to prepare for the future upgrades of ATLAS and LHCb, to consolidate our strong participation in our neutrino programme, to deliver our commitments and exploit the first physics from the AION project and MAGIS experiment, and to undertake generic hardware research and development. The opportunities offered by this exciting physics programme will not only drive the forefront of discovery, but also provide substantial impact to local enterprises and on public engagement. The beneficiaries of this research are the >50 members (academics, post-docs, engineers, technicians and PhD/MPhil students) of the Cambridge High Energy Physics group, all members of the many collaborating institutes in the UK and world-wide, CERN, the world-wide HEP theory community, STFC, our other funders, our collaborators, our undergraduate students, school children, teachers and the general public.

UKRI Gateway to Research · FY 2025 · 2025-09

Challenge Liver disease is the most rapidly increasing cause of death in the UK. Transplantation remains the only treatment for end-stage disease, but it is limited by organ supply. This challenge becomes more pronounced for diseases with no other treatment options, such as disorders of the bile ducts in the liver. The bile ducts form a network of tubes that transfer toxic bile. When they break down, bile damages the surrounding tissue, causing liver failure. Biliary diseases are the leading cause for liver transplantation in children, a major indication for transplantation in adults and a cause of liver failure in ~30% of transplanted livers. Context I have been working on addressing this challenge since 2017. I generated lab-grown (bioengineered) bile ducts and bile duct cells and used them to repair damaged ducts in mouse models and in human livers (cell therapy). These livers were not used for transplantation but kept alive outside the body using a method called machine perfusion, which uses pumps to maintain blood through the organs.   During the first part of my fellowship, I collaborated with industry (Bilitech LTD) and the UK Cell and Gene Therapy Catapult (CGTC), ensured that the cells met safety and quality standards for transplantation in humans, and upscaled my lab-grown ducts to human size. I tested the efficacy of lab-grown, human-sized duct prototypes with pilot pig experiments and completed successful preclinical testing of cell therapy for acute bile duct diseases (where injury stops after the damage has occurred). This technology is now ripe for clinical translation. In parallel, I tested cell therapy in animal models of chronic disease, where injury persists even after the ducts are destroyed. Transplanted cells could not survive in this toxic environment, but I discovered that using a drug called rapamycin could moderate injury and make the tissue more receptive to cell therapy. Furthermore, I discovered that the hostile environment changes the cells so that they lose their healing capacity (reprogramming), but this can be prevented using a cutting-edge technique called epigenetic CRISPR editing. My renewal proposal is the natural continuation of this work. Aims Advance lab-grown ducts and cell therapy for acute bile duct diseases to first-in-human studies. Optimise the efficacy of cell therapy for chronic disease, using the knowledge from the first part of my fellowship. Objectives Pursue regulatory approval for first-in-human studies for acute biliary diseases, supported by Bilitech and CGTC. Develop drugs enhancing cell therapy, in chronic biliary diseases. I will start with testing the efficacy of rapamycin in mice and machine-perfused human livers. Prevent cell changes after transplantation, with epigenetic CRISPR editing to prevent loss of their healing capacity. I will test these cells in mice and machine-perfused human livers. Potential applications and benefits This work will provide the first alternative to liver transplantation for patients with biliary disease. Repairing liver grafts with damaged ducts with cell therapy will increase organ supply and shift the paradigm for transplantation medicine. The transferrable technology generated will be applicable to multiple organs/cell types and advance the field to next-generation cell therapies with epigenetically-modified cells and treatment-enhancing drugs. Pursuing approval for first-in-human studies will map the regulatory landscape and set a point-of-reference for future cell therapies. Industry involvement will reinforce the UK’s leading position in cell therapy manufacturing, and promote economic growth.

UKRI Gateway to Research · FY 2025 · 2025-09

The last decade has seen an explosion of AI with spectacular advances in recent years that have brought AI and its use to the everyday life of many. Its methodologies are advancing fast and AI tools are becoming more and more sophisticated. Yet, there are many problems that AI could help solve but where the communities of AI and domain specialists have not yet met to explore and scope the possibilities and a wide range of potential users who have had little experience of machine learning and other AI tools.   The primary goal of our proposed programme of activities under the banner “AI and the Mathematical Sciences” will foster the interaction, collaboration and exchange of knowledge between the AI community and non-AI communities with the goal to encourage wider use of new AI capabilities both within the mathematical sciences and beyond. Mathematics and statistics form strong pillars of data science and AI. From that point of view, AI is an extension of the mathematical sciences. On the other hand, AI has the power to support with mathematical science research.  As tools become ever more powerful, they can help generate conjectures, optimise code, reduce computational complexity, and even suggest proofs. The activities in our programme will thus “export” AI out from the mathematical sciences to other domains such as medical sciences, social sciences, humanities, and to business, industry and government (BIG).  Or equally, activities may be directed at communities of mathematicians to tackle their pressing problems, and AI is thus “imported”. With all these interactions, scientific discoveries in the domain areas will be accelerated with the use of new AI tools. They will also foster strong inter-(and intra-)disciplinary partnerships by bringing together AI and non-AI communities.   The mathematical sciences also play an important role in the development of the AI tools themselves with more subject areas being drawn in to improve and control AI systems. As well as statisticians and numerical analysts, more theoretical areas such as algebra, geometry and topology are increasingly being employed to finetune AI pipelines. To foster these interactions and to draw in more mathematical scientists to apply their knowledge and expertise to AI challenges is a further goal of “AI and the Mathematical Sciences”.   Co-organised by the International Centre (ICMS) in Edinburgh, the Isaac Newton Institute (INI) in Cambridge, and the UK Knowledge Exchange Hub for the Mathematical Sciences (KE Hub) operating virtually, our programme of activities will draw on established UK-wide networks of mathematical scientists supported by professional research and innovation enablers.   In this first phase, a portfolio of activities ranging from workshops, schools, hackathons, summits, and challenge meetings are planned. These activities will increase adaptation of AI in a number of non-AI science communities including economics, finance, engineering, social sciences and biomedical sciences. In addition, we will deliver training, establish a new virtual Working Group and some “How to use AI” guides, and develop and provide access to pump-priming project funding that should enhance the take up of AI by academics in the mathematical sciences in their KE activities. Ultimately, we envisage a step change in the integration of AI and the mathematical sciences for the benefit of scientific research and UK PLC.    

UKRI Gateway to Research · FY 2025 · 2025-09

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 2025 · 2025-09

This project aims to explore wider stories and connections within the British Museum collection by conducting the first detailed technological study of some of Egypt’s earliest metal objects found in funerary contexts. Using advanced non-invasive analytical techniques, the research will evaluate manufacturing methods, technological choices, and material selection behind metal vessels and (model) tools, as well as their role in funerary practices. Representing some of early Egypt’s most significant material culture, these assemblages remain poorly exploited from a museological perspective. Their holistic examination and interpretation through the lense of ‘object itineraries’ affords tremendous potential to understand their makers and owners, thus developing engaging narratives beyond their artistic appeal. Furthermore, this opens novel possibilities for museum-based research to examine interactions between early civilisations in the region through technological exchange. As a pilot study, metal objects from the mid-third millennium BCE Royal Cemetery of Ur, Mesopotamia, will be compared. This will support future museum exhibitions and collaborations telling new stories about these under-researched objects in the collection. The research will provide unprecedented insights into the evolution of metal craft traditions and their integration into burial assemblages, helping to reframe traditional understandings of Egyptian funerary archaeology largely focused on beliefs about the afterlife. By creating detailed digital models of the objects, the project will make these artifacts accessible for global audiences. It will establish a new methodological framework for ancient metal studies, contributing to a comprehensive database and offering innovative pathways for research and outreach in Egyptology and archaeometallurgy

UKRI Gateway to Research · FY 2025 · 2025-09

The history and heritage of the discovery of environmental change and the interpretation of place in the East of England aims to show how local and global understandings of climate and the environment have been created in the east of England, by exploring the sites, museum collections and academic research groups that have delivered new understandings of place and changing climate in this region, since the early twentieth century. It takes advantage of several archival and museum collections of documents, instruments, specimens and sites, to invite innovative research that investigates how deeper understandings of place in the east of England were developed over the last one hundred years. The project will offer the student the opportunity to work across two or three areas of focus, including: 1) archival research on scientific studies of long-term environmental and climatic change 2) fieldwork drawing on approaches from the humanities including historical geography to establish a study of climate in place, examining one or more archaeological sites and communities in the east of England to explore how academic researchers changed understandings of place and worked with local communities at long-term research sites to relate different elements of climate, agriculture and landscape 3) the treatment of climate through geological specimens, scientific instruments, and archaeological research and displays in museums, exploring how collections have been assembled, used, curated and interpreted to establish changing perspectives on place and time, and how climate and place have been represented. Its outcome will be a pioneering study of how long-term global environmental change relates to the region.

UKRI Gateway to Research · FY 2025 · 2025-09

Sustainability is the great challenge of our generation. We produce energy in an unsustainable manner, with green energy sources still in the minority. Once this energy is produced, most of it is wasted due to inefficient use, something everyone has experienced when their laptop heats their lap rather than harnessing all available energy to run faster. The only way to maintain our standards of living while making sure that we do not create cataclismic changes to Earth's climate and environment, is to provide a science and technology-driven solution to the energy challenge. Some say that we live in the silicon-age, the material that powers computers and solar cells, and humanity has lived through multiple other "material ages", such as the stone or iron ages, that powered earlier human technological developments. This project asks: what materials will power the next sustainable age for humanity? We know of exotic materials, called superconductors, that can carry currents without energy losses. These materials could dramatically reduce energy waste. What is the challenge? The currently known superconductors only exist at extremely cold temperatures or extremely high pressures, precluding applications. We also know of materials, called organic semiconductors, that could be used to dramatically improve the efficiency and reduce the cost of solar cells and light emitting diodes compared to conventional materials like silicon. What is the challenge? We are yet to identify optimal organic semiconductors that can be properly integrated in solar cell or lighting devices. In this project we propose to discover the "sustainable age materials" for the next stage of human development. The experimental discovery of materials is a slow, costly, and often serendipitous process. Instead, we propose to discover new materials in a virtual laboratory, powered by the solution of the equations of quantum mechanics, which describe the fundamental microscopic behaviour of matter. The computational design of materials provides microscopic insights at small cost and with fast turnover, making materials discovery a predictive, rather than a lucky, process. As quantum mechanics is a theory that describes all of visible matter, from a single hydrogen atom, to a strand of DNA, to a complex material, the computational tools we develop for materials discovery are applicabable to all sorts of materials science problems. In the first stage of the Future Leaders Fellowship, we have discovered several record-breaking materials for energy applications, as well as the best X-ray detector material to date, which could help minimise the negative side effects of CT scans in hospitals. During the Fellowship Renewal, we propose to extend our work to other energy materials, highlighting superconductors for low-power electronics applications and organic semiconductors for solar cells and light emitting diodes. These developments will help accelerate the transition to the new sustainable age.

UKRI Gateway to Research · FY 2025 · 2025-09

Between the 17th and mid 19th-century, the Maratha-ruled court of Thanjavur, the last great dynasty of Sanskrit patrons before the establishment of British rule in India, richly contributed to the flourishing of Sanskritic intellectual culture and fine arts. Recently unearthed evidence suggests that most of the Sanskrit works produced under their patronage were composed in the nexus of brahman settlements (agrahara) and monasteries (ma?ha) located in the Kaveri river delta, a fertile region of southern India hosting, among others, large communities of erudite brahman scholars writing in Sanskrit. However, due to the still prevalent narrative according to which traditional Sanskrit scholarship ‘died out’ on the eve of the modern era, Indological research has largely neglected the key role of these peripheral institutions as stand-alone hubs of a sophisticated Sanskrit intellectual life in the Tamil region. This project brings together historians and philologists with expertise in early modern India to fill this important gap and conduct the first large-scale investigation of how these institutions and their networks of innovative scholars interacted and cooperated in the production of Sanskrit expert knowledge (philosophy, theology, devotional literature, belles-lettres, etc.) in the long eighteenth century. Our team will produce the first extensive survey of brahman settlements and monasteries in the Kaveri delta in the prolific period 1650-1800 based on manuscript collections, library catalogues, and epigraphical records. We will make use of data analysis, prosopography, and collaborative specialist readings to: a) understand how these institutions functioned as intellectual communities, both internally and in relation to the court and the several Tamil-speaking centres of learning and religious life in Tamilnadu; b) shed light on the lineages of families, teachers, pupils, and patrons that created the complex networks of Sanskrit expert knowledge in the region; and c) answer key questions about prominent Sanskrit authors active in these communities clarifying their disciplinary affiliations, intellectual practices, and most influential works. By pooling expertise and knowledge of different disciplinary areas and languages, our international team will gain a fuller picture of Sanskrit as a literary language in the Tamil-speaking region of the Kaveri delta. The project will also highlight the still poorly understood role played by Sanskrit expert scholars in the production, transmission, and dissemination of works and ideas in non-courtly settings. Our work will yield important insights into the social history of Sanskrit intellectual cultures and highlight the dynamism of India’s intellectual history in the century leading into the age of British colonialism. The project will also directly feed into the study of modern and contemporary Indian history as many of the institutions, lineages, and scholarly traditions studied in this project survive to the present day. Based at the Faculty of Asian and Middle Eastern Studies at the University of Cambridge, the project will produce a shareable database of works and authors, one co-edited volume, one special issue, articles in peer-reviewed journals and popular media, a website, and public talks in interactive spaces.      

UKRI Gateway to Research · FY 2025 · 2025-09

The Problem Language is the foundation for learning most other skills. To learn from spoken language, children must understand speech, which requires both sensory (hearing) and cognitive (language) abilities. Understanding speech is a challenge for many children for multiple reasons, and the resulting impact on their learning is not fully recognised or understood. A typical primary school class will contain children with reduced access to auditory information. Many of these children will not have been identified: newborn hearing screening does not detect mild or transient hearing loss, and hearing screening at school entry is no longer routine. Previous research has been inconclusive about whether mild/transient hearing loss affects children's language development. However, teachers report that children with mild-to-moderate hearing loss find it challenging to listen in noisy environments. They also suggest that the impact of mild hearing loss on speech, language and literacy development is often underestimated. Recent estimates suggest one in fifteen children start school with language difficulties that are unexplained by other biomedical conditions (such as diagnosed deafness/hearing loss or autism spectrum disorder). Difficulties with speech perception (hearing and recognising speech sounds) are often proposed as a potential cause of difficulties with learning language. However, there is limited systematic evidence concerning the relationships between mild/transient hearing loss, speech processing (converting speech sounds into language), spoken language learning and educational outcomes, highlighting the need for objective investigation in the wider primary school population. Our Solution This project takes a large-scale approach to this problem: assessing the hearing and speech processing abilities of whole classes of children, rather than targeting those with pre-existing diagnoses. This will allow us to establish the prevalence and co-occurrence of mild/transient hearing loss and speech processing difficulties at scale; and to assess the longer-term impact of these conditions on language outcomes, literacy and educational attainment. It will go beyond traditional measures (e.g. vocabulary) to assess the speed with which they recognise words, which is essential for day-to-day conversations and accessing education. In addition, we will measure how much children benefit from seeing a speaker's lip movements when listening, and consider whether these benefits support language development. What we will do We propose to administer computerised tests of hearing and speech listening to whole classrooms of children (~2400 children overall). Children will complete these assessments during engaging science education sessions, using tablets and headphones. We will also measure children's language and reading skills (e.g. their vocabulary knowledge), other cognitive abilities (e.g. paying attention) and then follow these children over two school years to determine how hearing and spoken language skills relate to standardised classroom outcomes (e.g. phonics check scores). How this will help The proposed project will help us gain a better understanding of the prevalence and impact of mild/transient hearing loss on children's spoken language skills, including speed of word processing. Our findings will help determine the support needs of children at risk of hearing and language difficulties, with a view to impacting clinical and educational policies to support children to reach their maximum potential. During the project, participating children will directly benefit from our science education sessions. We will also provide teacher training and data to help the schools we visit to identify and support individuals with hearing or language difficulties.

UKRI Gateway to Research · FY 2025 · 2025-09

Lactation is a cornerstone of mammalian life, playing a pivotal role in the growth and development of offspring. Breastfeeding offers a wealth of benefits for mothers and infants. For mothers, it reduces the risks of breast and ovarian cancer, lowers the likelihood of postpartum depression, and strengthens the bond with their infants. For babies, breastmilk provides tailored nutrition and immune protection, reducing the risk of infectious diseases and fostering healthy development. In the long term, breastfed infants have a reduced risk for diabetes and obesity. The successful establishment of breastfeeding depends on the accurate and timely development of the mammary gland, a process driven by complex hormonal and transcriptional signals. Despite its importance, much remains unknown about the mechanisms underlying lactation, particularly the links between early postnatal nutrition and the origins of health and disease. This knowledge gap is particularly concerning given the increasing incidence of these conditions in an ageing global population. Breastfeeding is vital not only physiologically, but also culturally and evolutionarily across all mammals. Disparities in breastfeeding rates between developed and developing countries, and across socioeconomic groups, create inequalities for mothers and babies. Breastmilk is economically and environmentally advantageous compared to formula. It offers sustainability and lower health risks, yet breastfeeding is often overlooked in global health policies. Climate change further threatens maternal and infant nutrition, especially during disasters, when safe formula feeding becomes challenging due to disruptions in water, electricity and supply chains. This highlights the need to enhance our understanding of lactation biology to safeguard maternal and infant health in a changing world. The overarching aim of my research is to expand our knowledge of early postnatal nutrition and the biological mechanisms that govern lactation. Unlike traditional studies, my approach explores the mother, offspring, and milk as an integrated system, providing a holistic view of lactation biology. A significant focus of this work is on imprinted genes, which are crucial for embryonic and placental development but remain largely unexplored in relation to mammary gland function. Another novel aspect of this study is exploring inter-organ communication involving the mammary gland, both sending and receiving signals. Specifically, my objectives are: Investigate the function of candidate imprinted genes on mammary gland development, lactation and offspring growth. Study imprinted gene protein products in human breastmilk. Explore maternal inter-organ communication between the mammary gland and other maternal organs, to understand how these signals influence lactation and maternal health. By uncovering the fundamental processes that regulate lactation, this research has the potential to revolutionise our understanding of early postnatal nutrition, improve formula for infants, identify genetic factors that enhance milk supply, and shape public health strategies. Leveraging advanced genetic and molecular tools and integrating data from both mouse models and human breastmilk, my pioneering approach could uncover new pathways that drive infant growth. Ultimately, these discoveries have the potential to transform the lives of pre-term infants, those facing feeding challenges, and mothers unable to breastfeed, addressing critical global health issues and advancing the field of lactation science.