University of Cambridge

UKRI Gateway to Research · FY 2027 · 2027-03

Context and Challenge Pancreatic cancer (PDAC) is lethal for most patients, with fewer than 10% surviving more than 5 years. This is largely because the disease is diagnosed late, when it has spread to other organs, a process known as ‘metastasis’. For metastatic patients, treatments are ineffective. Additionally, PDAC is characterised by poorly understood features that promote disease progression and therapy resistance, including non-cancerous cells known as cancer-associated ‘fibroblasts’ (CAFs) that constitute most of the tumour. Our Lab’s goal is to understand how cancer cells and CAFs cooperate to drive PDAC progression, and to apply this knowledge to group patients and develop tailored therapeutics. I previously discovered that CAFs exist in two major states: myofibroblastic (myCAFs) and inflammatory (iCAFs). Over the past three years, my laboratory extended this work, systematically studying processes operating in CAFs and cancer cells, and the crosstalk between these populations. In this manner, we identified new PDAC vulnerabilities, including promotion of metastasis by a subset of myCAFs, and cancer cells’ DNA alterations-dependent signalling that shape CAF composition. These findings are beginning to unravel the complex processes that govern cancer cell-fibroblast signalling in one of the deadliest and enigmatic cancers. However, our knowledge remains largely limited to primary pancreatic tumours rather than metastases, which are the main cause of patients’ death. Therefore, we will build from our work to understand the functional heterogeneity of fibroblasts in metastatic PDAC. This knowledge is required if we are to develop better ways of diagnosing PDAC earlier and treating it more effectively. Objectives and Aims Our knowledge of PDAC biology is largely limited to tumours with two DNA alterations known as Kras-G12D and mutant-p53. However, my work has highlighted how additional alterations shape CAF composition, PDAC progression and therapy response. I will build from this work to understand how distinct DNA alterations impact malignant cell-intrinsic and -extrinsic drivers of PDAC metastasis with the goal to develop therapeutics for groups of patients. To this end, I will combine patient-relevant organoid-derived models with innovative mouse models for depletion of specific fibroblast populations. We will focus on metastases in the liver and lungs, which are most prevalent in patients, and PDACs with combinations of four DNA alterations common in patients: Kras-G12D, mutant-p53, Smad4-loss and Cdkn2a-loss. Objective 1: Identifying tumour-promoting cancer cell-fibroblast interactions in metastatic PDAC. We will analyse matched primary tumours and metastases from organoid-derived mouse models to identify cancer cell-fibroblast drivers of PDAC progression. Candidate targets will be prioritised according to strict criteria, including validation by orthogonal approaches (WP1-WP2), human biology (WP3) and availability of pharmacological inhibitors. Objective 2: Targeting tumour-promoting cancer cell-fibroblast interactions in metastatic PDAC. We found that iCAFs are enriched in Smad4-deleted PDAC. We will thus target cancer cell-iCAF crosstalk leveraging mouse models for iCAF depletion (WP4). This work, together with Objective 1, will guide the design of pharmacological strategies to target tumour/metastasis-promoting cancer cell-fibroblast crosstalk in PDAC (WP5). Applications and Benefits My work will identify biological processes underpinning metastasis and pinpoint new treatment targets for PDAC. Our models and datasets will be made available directly to the global research community, ensuring that they are widely accessible and deployed. As similarities across malignancies exist in terms of fibroblast functions, and metastasis is the primary cause of death of cancer patients, my work could benefit the broader scientific and clinical community.

UKRI Gateway to Research · FY 2026 · 2026-09

This grant aims to advance the frontiers of knowledge in particle physics through several broad initiatives. We will interpret data from colliders to uncover new particles and forces, aiming to address some mysteries of the Standard Model. Our approach will include unprecedented precision in calculating complex quantum processes relevant to particle colliders, using analytical methods, computational techniques, and the latest experimental measurements. Beyond theoretical advancements, this effort will support large-scale experiments at CERN and other locations by providing state-of-the-art theoretical physics calculations. Our key goals include: Enhancing the precision of Standard Model predictions. Improving the parameterisation of proton constituents. One of our techniques involves discretising space-time to simulate quantum processes on supercomputers and, in the future, quantum computers. These calculations necessitate specific theoretical advances, which we will pursue diligently. Quantum field theory, the foundation of known particle interactions, remains rich yet underexplored. There are many aspects whose meaning and foundations are still unclear. We will explore these areas, pushing our understanding of various topics within the theory, including approaches that extend beyond quantum field theory, such as ambitwistor strings. Additionally, we will make strides in the foundational theory of quantum gravity, which has long eluded physicists. Our investigations will encompass cosmology, black holes, and wormholes, since these are theoretical arenas where significant progress can be made.

UKRI Gateway to Research · FY 2026 · 2026-09

Our ability to fight infections relies on the capacity of professional immune cells to defend our body and on the skills of individual cells to defend themselves. The contributions of professional immune cells to innate and acquired immunity have received much attention. Much less is known about the principles of cell-autonomous immunity. Inspired by the ability of unicellular organisms to rely exclusively on cell-autonomous defences, we investigate how mammalian cells protect their interior against bacterial invasion (reviewed in Randow, Science 2013). Our recent work has revealed a novel principle of cell-autonomous immunity. We discovered that mammalian cells convert cytosol-invading bacteria into pro-inflammatory and anti-bacterial signalling platforms through the deposition of host proteins into polyvalent arrays at bacterial surfaces. The deposition of M1-linked ubiquitin chains by the E3 ubiquitin ligase LUBAC induces anti-bacterial autophagy and pro-inflammatory NF-kB signalling (Noad, Nat Microbiol 2017; Ravenhill, Mol Cell 2019), while the deposition of GBPs, a family of interferon-induced GTPases, recruits and activates Caspase-4, resulting in pyroptotic cell death and the release of IL-18 (Wandel, Cell Host Microbe 2017; Wandel, Nat Immunol 2020). The project will focus on the transformation of bacterial surfaces into signalling platforms. Potential projects include the characterization of novel E3 ligases that ubiquitylate bacteria, the investigation how GBPs detect bacteria, and the identification of novel anti-bacterial effector mechanisms triggered by polyvalent protein coats on bacterial surfaces.

UKRI Gateway to Research · FY 2026 · 2026-09

Recent discoveries of numerous sub-structures in protoplanetary discs have dramatically changed our perception of planet formation and protoplanetary disc evolution. An amazing richness of structures revealed to us by ALMA and direct imaging surveys - multiple axisymmetric gaps and rings, spiral arms, non-axisymmetric arcs, etc. – challenged many ideas that we had about these discs earlier. While there are many agents that could be responsible for the production of these features, one of the most exciting (but also most natural) possibilities is that they are ultimately driven by planets, through their gravitational coupling with the disc. This provides a clear motivation to bring the study of disc-planet coupling – a subject with the long history of successful predictions – to a whole new level, to be able to match the intricate details of what we find observationally. One area that has received insufficient attention so far but is very promising for explaining many observations is the gravitational coupling between the planets on non-circular orbits – eccentric and/or inclined – and the disc, and the impact this interaction has on the disc. Unlike the orbital evolution of the planets themselves, this area has not been so well developed for non-circular planets, but holds great promise for explaining many observational puzzles and for making interesting observational predictions. The goal of this proposal is to advance our understanding of the non-circular planet-disc interaction through a series of projects of increasing complexity and involving both large-scale numerical simulations (in 2D and 3D) as well as theory. We will investigate the morphology of the wave perturbations produced by planets on non-circular orbits, and will explore how these waves are excited, propagate through the disc and damp, ultimately driving disc evolution. We will study the process of gap opening and disc warping by eccentric and inclined planets across the range of various relevant physical parameters and for different regimes of disc-planet coupling - both linear and non-linear. In the process, we will make predictions for thermal sub-mm dust emission from discs, kinematic signatures of planets in molecular line emission, and for disc images in scattered light in near-IR, which will be utilized for interpreting protoplanetary disc observations. The success of this project rests on our deep familiarity with the subject and on our extensive experience in the relevant areas, as well as on our robust methodology. Our simulations will be closely accompanied by theory and will be analyzed from the theory perspective, by focusing on key physical processes and deliverables that deepen our understanding of the underlying processes (e.g. re-distribution of the angular momentum between the planet-driven density waves and the disc). This project is novel, ambitious and timely in light of the wealth of data that is provided to us by the facilities such as ALMA, JWST, and other channels through which we study protoplanetary discs and planet formation.

UKRI Gateway to Research · FY 2026 · 2026-08

This project will develop a new methodology to create the first geocoded record linking of all censuses for England and Wales (EW) between 1841 and 1921 and use this unprecedented longitudinal dataset to analyse internal migration, urbanisation, and women's work and demographic outcomes. It combines advances in Machine Learning (ML), Handwritten Text Recognition (HTR), document understanding, geocoding, and both probabilistic and ML record linking. By bringing together the expertise of leading researchers in these fields, The National Archives, and the two largest providers of census data, FindMyPast and Ancestry, we will significantly improve what is currently possible for census linking and offer the first set of high-precision, low-bias links for EW. Data for Scotland is held separately and still undergoing work by Digitising Scotland. If funded, we hope to have more leverage to convince them to share their data so we can include Scotland in our analyses. Our methodological development will create a new class of linking approach altogether – based on token-level probability matching – which has the potential to significantly increase current matching rates and quality. We will also improve the linkage of women by pioneering the inclusion of marriage registers at scale to identify married women across censuses, and we will augment the census by geocoding all individuals to the streets and buildings in which they resided, allowing for even more granular spatial analysis. Our new data will transform the way we study internal migrations. Studies of nineteenth and twentieth-century migratory patterns have primarily relied on the comparison of places of birth and enumeration at each census, which prevents the analysis of individual and time-dynamic components of migrations. Using longitudinal data, we will finally be able to uncover these very fine-grained migratory paths for every decade, allowing us to provide a much fuller account of the economic, lifecycle, and geographic determinants of internal migrations in a period of rapid social change and sustained urbanisation. Longitudinal geocoded data will also transform our understanding of urban growth. We will be able to track residential movements within highly specific urban spaces (down to the building level) on every census date, allowing us to provide a much fuller picture of residential segregation patterns, changing urban systems, urban morphology, and their interactions with transport infrastructure and institutional settings. Finally, we will be able for the first time to reconstruct individual marriage and fertility timelines over long periods on a national scale and at a very high level of spatial disaggregation. Currently, the interaction between women’s work, marriage, and fertility cannot be satisfactorily studied because we cannot observe the occupational and household status of women before marriage and during their childbearing years. We will now be able to identify the precise timing of marriage and dramatically improve our estimates of parity progression to study this phenomenon with unprecedented precision. We will make all the links available to researchers, unlocking an infinite number of future projects and research questions and creating a fundamental new resource for British historians, economic historians, demographers, economists, sociologists, and many more. Our partners, genealogists, and the broader public will benefit from a much-enhanced ability to find data about their ancestors using our linked data. We will also develop with secondary-school teachers ready-for-classroom pedagogical resources and lesson plans using our new data to improve the teaching of history and geography.

UKRI Gateway to Research · FY 2026 · 2026-08

‘Critical’ metals are those which modern society relies upon for economical and technological progress but have inherent supply risks. Many critical metals are facing rising demand due to their use in green energy transition technologies (e.g. wind turbines, electric vehicles), in particular rare earth elements (REEs) and lithium (Li). These metals have become increasingly topical in the past few years as countries seek to diversify and secure their supply chains. In nature, many REE and Li deposits are associated with igneous rock types. For example, alkaline silicate intrusions and associated carbonatites are the world’s major hosts of REEs, whereas granitoids and pegmatites are a major Li source. However, we lack a detailed theoretical understanding of how REE or Li behave in these igneous systems, particularly the magmatic processes that control their enrichment and may subsequently lead to mineralisation. This knowledge is essential to diversify the critical metal supply, support technological progress and, for green energy materials, meet net-zero targets.  My project tackles this timely societal and geological challenge through an ambitious extension of a traditionally metamorphic geology tool (phase equilibria modelling) to an igneous and economic geology problem, creating a process-based understanding of magmatic critical metal deposits, with a particular focus on REEs and Li. My project takes an observation-driven phase equilibria modelling approach to understand the magmatic processing of critical metals. Natural case studies (e.g. Greenland, southwest England and West Africa) provide a crucial reference frame for all modelling. Fieldwork is the starting point to collect rock samples and make observations, followed by detailed geochemical analysis at the whole-rock, thin section and individual mineral scale (using e.g. electron probe microanalysis and laser-ablation trace element mapping). We then integrate phase equilibria modelling, using a new suite of thermodynamic models developed during this project, to understand the observed major and accessory mineral behaviour as a function of a range of physio-chemical variables (e.g. pressure, temperature, oxidation state). This approach allows us to decode the formation conditions of the igneous system of interest. By simultaneously tracking the trace element evolution of all phases via partition coefficients, we have developed a powerful approach to quantify the controls on the ‘sweet-spots’ for magmatic critical metal enrichment in nature. During the renewal of this fellowship, our work will focus on extending our thermodynamic modelling capabilities to include carbonatite and fluorine-bearing melts, developing methods to account for ‘accessory’ minerals (e.g. eudialyte) that can host substantial REEs, and applying our workflow to Li-bearing granites following a focus on REEs in the first years of the project. By understanding the magmatic processes that have led to world-class critical metal deposits such as the REE-rich Ilimaussaq intrusion in Greenland, or the Li-rich Cornwall granites in the UK, we can predict where to locate other similar deposits. To maximise the potential of our research, this project brings together a team of globally-renowned academic and industrial project partners in addition to the research team, providing world leading expertise spanning from the pluton scale down to mineral grains, and from critical metal policy to active industry. The innovative framework pioneered by this fellowship can be generalised to other magmatically-processed critical raw materials, providing a bold long-term program of research that could revolutionise industrial approaches to critical metal exploration in igneous settings.

UKRI Gateway to Research · FY 2026 · 2026-07

The densely populated central and eastern Mediterranean is Europe’s most tectonically active area. Lithospheric subduction and deformation and the interactions of the variable-thickness lithosphere with the underlying asthenosphere give rise to earthquakes, volcanoes and ensuing tsunamis. Understanding the structure and dynamics of the lithosphere and underlying mantle that control the active tectonics, natural hazards and, also, the distribution of the region’s natural resources is an important outstanding challenge. Recently, the area has been instrumented densely by AdriaArray, the largest structural seismology experiment in Europe that comprises over 1000 broadband seismic stations and provides unprecedented data sampling of the region. Project Lead (PL) Lebedev and Project co-Lead (PcL) Rondenay are members of AdriaArray and its Steering Committee, have contributed to its deployment and operation and have full-dataset access (not public at present). The proposed project exploits the synergy of the leading expertise of the PL and PcLs in seismic tomography and receiver-function analysis, the enormous volume of unique new data, and the collaboration with the broader AdriaArray team. The project’s goals are to 1) combine the resolving power of waveform and array tomography, receiver functions and thermodynamic inversion and map with high regional resolution: ·        azimuthally and radially anisotropic seismic-velocity structure of the crust and upper mantle; ·        thermal structure of the lithosphere and underlying mantle; ·        the depth and structure of the lithosphere-asthenosphere boundary (LAB); 2) obtain new insights into the mechanisms of lithospheric extension, collision and subduction in the region; 3) obtain new evidence on how the structure and dynamics of the lithosphere and underlying mantle control ·        seismicity; ·        volcanism; ·        generation and distribution of the mineral  and geothermal energy resources, to help to de-risk resource exploration. In order to capitalise on the unprecedented data sampling, new seismic and thermal imaging methods will be developed. Waveform-tomography and array-tomography methods will be integrated, aiming to maximise the resolution of the imaging beneath the entire array, including its periphery. Regional and teleseismic S-wave traveltime data, measured using an accurate, recently developed automated picker, will further increase the resolution. Thermodynamic inversions of seismic data directly for temperature will use computational petrology and thermodynamic databases and reduce biases due to the non-uniqueness of intermediate seismic-velocity models. Receiver-function measurements from across the region will provide essential complementary information on the depth of the crust-mantle boundary (the Moho) and the depth and fine structure of the LAB, reducing the non-uniqueness and increasing the accuracy of the seismic and thermal models. Lithospheric controls on the uneven distribution of intraplate seismicity will be investigated, aiming to produce useful co-variates for probabilistic seismic hazard models. Lithosphere-scale thermal models will yield maps of crustal temperature for de-risking geothermal energy exploration. The locations of rare-earth and base metal mineral deposits in the region relative to lateral variations in the lithospheric structure will be investigated. The high-resolution mapping of the lithosphere-thickness contrasts will provide tests and refinements for the models of the natural resource generation and distribution. This timely project takes advantage of an important, unique new dataset, collected at no cost to it. It will use the extraordinary data sampling to investigate the basic mechanisms of lithospheric dynamics and, also, deliver societally and economically important inferences on the lithospheric controls on natural hazards and resources.

UKRI Gateway to Research · FY 2026 · 2026-06

Coral reefs support over 25% of all marine species and provide ecosystem services worth over US$2.7 trillion. These reefs exist because corals produce calcium carbonate skeletons, which accumulate to create reef structures. Both coral survival and skeleton formation are threatened by anthropogenic climate change, particularly temperature and ocean acidification. While significant effort focuses on heat stress impacts, a crucial gap remains in understanding if corals will continue to calcify under future ocean acidification. The core challenge this project addresses is our fundamental lack of mechanistic understanding of coral skeleton formation. We lack important knowledge on how corals build their skeletons at a microscopic level, and why some species might be inherently more resilient to ocean acidification than others. This missing mechanistic insight prevents us from systematically identifying corals that might survive future conditions and continue to build the reefs of tomorrow. Our project will fill this major knowledge gap by conducting comprehensive in-vivo measurements of coral calcification processes. Our central aim is to precisely characterise the composition and dynamics of the microscopic fluid compartments where corals build their skeletons – the ‘extracellular calcifying medium’ (ECM). The ECM's full composition has only been characterised once in-vivo, and the dynamics of its regulation have never been observed. Our comprehensive experiments will transform our understanding of this elusive micro-environment, which is responsible for forming the largest living structures on our planet. The specific objectives of our project are: To measure the composition of the ECM in three ecologically important tropical coral species, providing the first comprehensive data on its variability (WP1); To determine the dynamics of how ECM chemistry is controlled in real-time in response to changing environmental conditions (temperature, pH), revealing critical insights into regulatory mechanisms (WP2); To assess whether corals can adapt their ECM control mechanisms to future climate change by studying colonies cultured long-term under altered environmental conditions (WP3). Our approach is based on an innovative combination of inverted confocal microscopy and electrochemical microsensors. Our cutting-edge technology allows us to precisely position sensors and gather high-resolution, multi-parameter data on ECM chemistry and crystal growth within live corals. This technically demanding methodology is uniquely enabled by the world-leading expertise of Dr. Sevilgen (Researcher Co-Lead) and Dr. Dirk de Beer (Project Partner) in microsensor fabrication and application, complemented by the state-of-the-art coral culturing facilities at the University of Cambridge managed by Dr. Branson (Project Lead). Our integration within Dr. Branson's interdisciplinary 'Building Shells' project further ensures robust scientific and translational outcomes. The potential applications and benefits of this research include: Advancing Coral Research: By providing the critical data for next-generation biomineralisation models, our findings will enable more robust predictions of how corals cope with environmental fluctuations, improving the accuracy of future climate change projections for reef ecosystems. Informing Coral Conservation: Understanding the limits and potential for coral adaptation will inform the prioritisation of conservation and restoration strategies, assisting the selection of species with greater intrinsic adaptive potential. Broader Scientific Insights: Beyond corals, this project will yield foundational insights into the fundamental biological processes of biomineralisation, relevant to a wide range of marine calcifying organisms facing environmental change. This project will deliver critical, mechanistic knowledge essential for understanding, predicting, and ultimately safeguarding Earth's invaluable coral reefs in a rapidly changing world.  

UKRI Gateway to Research · FY 2026 · 2026-04

Stone tools were made for over three million years and by at least 15 different hominin (fossil and modern human) species. They were essential to their survival and constitute the most abundant evidence there is concerning the behaviour, culture and evolution of early humans. A single principle, however, underpinned the production of almost every stone tool: their capacity to cut. Indeed, almost every stone tool recovered from the archaeological record was most likely produced so another material could be cut, scraped, pierced or otherwise deformed. This includes the butchery of animals, carving wooden tools, and multiple other tasks where a sharp edge is employed to separate and puncture material. In turn, stone tools aided the survival and global expansion of hominin populations, provided significant adaptive pressure on cognition and culture, and are one of the few behavioural constants over the last 3 million years. In this sense, an understanding of stone tool functional design and the mechanics of their use gets to the heart of the most important debates in human evolutionary research. Given their importance, there would have been strong pressures favouring the design of stone tools that were reliable, durable and energetically efficient. Despite this, there is little research examining whether Stone Age populations actually produced functionally-optimised stone tools. In turn, our ability to discern the extent, nature and cause of any deviations away from functionally-optimised tools – including via widely reported alternative mechanisms, from cognitive evolution through to aesthetic intent – is equally limited. ‘Cutting-edge technology’ (CET) will directly address these gaps in our knowledge by exploiting advanced finite element analysis (FEA) techniques and fracture mechanics theory – regularly used by mechanical engineers to virtually design and test metal cutting technologies – and integrating them with the analysis of 3D-models of African Stone Age artefacts. Something which has never been attempted before within human origins research, despite there being decades of work into the mechanics of how modern metal tools cut. Indeed, function-related explanations for stone tool design choices represent one of the few hypotheses that can be directly and rigorously tested, and yet FEA remains absent from the arsenal of techniques available to prehistoric archaeologists. Two fundamental yet unresolved questions will be addressed by CET: 1) How does the morphology of stone tools influence their functional performance and cutting mechanics? 2) Were African Stone Age artefacts actually mechanically optimised and what influence would these relationships have had within wider behavioural contexts (e.g., cultural variation)? FEA models will virtually simulate the use and cutting-mechanics of Stone Age technologies during wood and meat processing – the two most widely evidenced early tool-use behaviours – using 3D-scans of artefacts from three Stone Age case studies. 1) Early Stone Age handaxes and cleavers from Olduvai Gorge, Tanzania. 2) Levallois flakes technologies from Middle Stone Age sites in East and southern Africa. 3)Middle Stone Age Still Bay projectile points from South Africa. Variation in the form of these artefacts, or comparisons between artefact types, will be aligned with modelled performance data, allowing assessment of design optimisation (or lack thereof) across >1.6 million years of stone tool production and diverse hominin species. Results will provide a fundamental shift in how stone artefact designs are investigated and provide unique insight into the behaviour, culture, evolution and cognitive capabilities of early humans in Africa.

UKRI Gateway to Research · FY 2026 · 2026-04

Summary Primary forests across Sub-Saharan Africa are under critical threat. Biodiversity loss, ecological degradation and climate related impacts are undermining climate resilience and sociocultural resources vital for local lifeways. The solutions to such loss are fraught, as exclusionary conservation models often conflict community-led approaches. These dynamics are starkly evident in Kenya’s Cheragnani Hills, where state-led efforts aiming to restore degraded forests through exclusionary governance models stand in contrast to community activists championing their own histories of environmental stewardship. Both approaches produce visions for the future grounded in simplified readings of the past. Conservation models aim to produce an imagined forested landscape void of human activity, whilst community activists risk basing their land claims on narrow interpretations of ethnic succession. Archaeological remains scattered throughout these hills challenge both of these views, revealing a deeply anthropogenic forest shaped by centuries of shared use. This project – Reimagining Forest Futures through Citizen Science Archaeology (REFFCA) – explores whether archaeology can make a practical difference to these debates. It aims to test how long-term perspectives on land use, settlement and belonging, produced and interpreted in collaboration with local communities, can support more inclusive and historically informed discussions about the forest’s future. To do so, it focuses on two key conservation blocks in the Cherangani Hills, where existing participatory forest management legislation remains ineffective and contested. It brings together archaeologists, citizen scientists, government forest officials and community members to co-produce new knowledge and stimulate policy-facing dialogue. The project has three main objectives: 1.     Co-design a research and training programme with community Citizen Scientists to explore how and if knowledge of the past can better engage with today’s conservation challenges. 2.     Generate new archaeological data on long-term human–forest interaction, including mapping historic and Late Iron Age features, and survey community views on how this heritage informs present and future land use. 3.     Facilitate public and policy dialogue through participatory exhibitions at forest stations and a policy workshop with senior forestry and county officials, using visual materials co-produced with Citizen Scientists. The project pioneers an integrated approach to archaeological and policy-relevant knowledge production by combining landscape surveys with community-led interpretation and feedback processes and public exhibitions. Data is co-constructed through Citizen Scientist engagement, with findings shared in accessible formats that inform academic, policy and public spheres alike, including peer-reviewed articles, a publicly available policy white paper, open-access spatial datasets and community-facing exhibition materials. The project offers a range of interlinked benefits. Participants will gain deeper knowledge of forest heritage, receive skills training and have the opportunity to contribute directly to policy conversations. Policymakers will benefit from historically grounded and socially embedded insights into how communities interpret and mobilise the past in shaping future visions of the forest. The wider public will access this heritage through engaging, visual formats that make the region’s deep history more accessible. For the academic community, the project provides a tested model of citizen-led, policy-relevant archaeology with potential to inform similar approaches in other conservation contexts.

UKRI Gateway to Research · FY 2026 · 2026-03

The human body consists of more than 250 specialised cell types. During embryonic development, this great diversity arises from a small group of equivalent cells known as the epiblast. In humans, the first specialised cell types develop from the epiblast over about 2 weeks, in a specific order and at specific time points. This period of development is critical for embryo formation and remarkably vulnerable as about 60% of pregnancies fail around this stage. Thus, a detailed understanding of this process is essential for both basic and applied research, yet remains limited due to restrictions on human embryo work. Decades of research in developmental biology have identified signalling molecules that instruct epiblast cells to become specialised. Nevertheless, these signals are often present well before the specialised cells emerge in the embryo, suggesting they are insufficient to fully explain how the human body develops. My key question is how cells respond to instructive signals at the right time during embryonic development. To address this, I established an experimental method reproducing early human development using pluripotent stem cells (hPSCs) in a dish. This is a simple and amenable for manipulations model to study human embryogenesis that avoids the use of actual embryos. Using my stem cell model, I discovered that the presence of a signal is insufficient to make them specialised. The stem cells must be prepared to respond to the signal (“competent”), otherwise they do not react or react wrongly. Moreover, they become responsive to different signals only at specific time points during development. Therefore, there must be a molecular mechanism “counting time” in stem cells that instructs them to become responsive at the right moment. I identified a cascade of regulatory proteins (transcription factors) sequentially activating each other with specific timing, acting as an internal timer in the human embryo. I propose that this internal timer instructs the epiblast to become responsive to the right signals at the right time. I hypothesize that the order in which the epiblast becomes responsive to different signals defines the timing when the respective specialised cell types emerge. In my project, I will reconstruct the molecular mechanisms that enable stem cells to respond to specialising signals at the right time. First, I will identify the components of the internal timer that instruct signal responsiveness. Second, I will investigate the instructive mechanism and how its failure leads to known human developmental defects. Finally, I will test how this system enables the stem cells to respond to signals inducing specialisation. Together, these mechanisms form an important developmental programme responsible for the formation of the human body, which has been difficult to study due to the lack of suitable experimental systems. My research will advance our understanding of early human development and developmental disorders. Importantly, knowledge of specialisation mechanisms will facilitate the establishment of efficient methods for generating specialised cells from stem cells in a dish for biomedicine, drug discovery, and disease modelling. Furthermore, my research will reveal the fundamental principles of cell specialisation that govern not only embryo development, but also physiological cell turnover and regeneration. Failures in these processes may contribute to degenerative diseases and age-related decline. Therefore, my work will facilitate the development of novel treatments and regenerative therapies. Ultimately, my research will contribute to fundamental and biomedical research for the benefit of society.

UKRI Gateway to Research · FY 2026 · 2026-03

Globally, about one in four deaths are related to unhealthy diets. Unhealthy diets cause obesity and chronic diseases such as diabetes, cancer and heart disease. Around two-thirds of UK adults and one-third of children live with overweight or obesity. Obesity and chronic diseases are more common in people living in poorer households. Ultraprocessed foods (UPFs) are industrially produced using methods that cannot be replicated at home. On average, UPFs make up at least half of the food people in the UK eat, with people living in poorer households eating more UPFs. About half of UPFs are also high in fat, salt or sugar (HFSS). Most current UK dietary policies support people to eat fewer HFSS foods. Many studies find links between eating UPFs and obesity and chronic diseases, although sometimes only for some types of UPFs. Some countries now tell citizens to avoid UPFs. In the UK, the current scientific evidence is not yet considered strong enough to include UPFs in guidance. This is partly due to uncertainty about the biological mechanisms linking UPFs to diseases. There is a high level of political and public interest in UPFs. If guidance to eat fewer UPFs were to be introduced, we would quickly need to know the best intervention mechanisms to support people to eat less harmful UPFs and more non-UPFs without exacerbating existing inequalities. There is also uncertainty about what these are. To address these uncertainties, we will bring together an interdisciplinary team to study the: ·              biological mechanisms linking UPF consumption to obesity and chronic diseases ·              intervention mechanisms to support everyone to eat less harmful UPFs and more non-UPFs We will start by exploring the overlap between UPFs and other food classifications, such as HFSS, to help determine what, if anything, is unique about UPFs and which types of UPFs are most harmful. We will study how eating different UPFs influences blood chemicals to identify particularly harmful UPFs and biological mechanisms of harm. We will look at how changes in UPF consumption relate to changes in markers of disease such as body weight and blood pressure. Next, we will explore how current approaches to support people to eat less HFSS food influence UPF intake. We will study the UK soft drinks tax, calorie counts on restaurant menus, and restrictions on less healthy food advertising. These operate via intervention mechanisms such as changing price (soft drinks tax), providing information (calorie counts) and reducing prompts to buy (food advertising restrictions). We will consider our results with those of others to create a comprehensive understanding of the best intervention mechanisms to support everyone to eat fewer harmful UPFs. Most approaches to supporting healthy eating focus on restricting less healthy foods by taxing, labelling or restricting advertising. These ‘negative’ interventions can be less acceptable than more ‘positive’ approaches such as subsidising healthier foods. We will use ‘systems thinking’ to work with stakeholders to generate new ideas for interventions to help people eat more non-UPFs. We will estimate impacts on disease and cost-effectiveness. Greater clarity on biological mechanisms linking UPFs to disease will help governments decide whether new guidance is needed. Greater clarity on the most effective mechanisms to help everyone eat less harmful UPFs and more non-UPFs will help governments know how to act. We will share our results with policymakers.

UKRI Gateway to Research · FY 2026 · 2026-03

Lake Kivu is located on the border of Rwanda and the Democratic Republic of Congo, along the western branch of the East African Rift, a region of active volcanism and high seismicity. The lake spans nearly 2400 km2 and contains nearly 60 km3 of methane (CH4) and over 300 km3 of carbon dioxide (CO2), dissolved in the deep and saline lake waters, from 250m- 485m below the surface. Upper waters of the lake are less saline and ventilated by inflow of cold but relatively fresh groundwater at 250-260m, leading to a strong, stable density stratification called the chemocline. The lake's unique stratification, combined with volcanic and tectonic activity, presents a natural risk of overturning known as a limnic eruption. Methane from Lake Kivu is extracted for electricity production in Rwanda by KivuWatt (owned by Contour Global, UK), who produce 26 MW, and Shema Power Lake Kivu (SPLK) (RW) who produce about 37 MW of power, with plans to increase the rate of extraction. This represents a very significant fraction of the energy needed for the 400 MW of power used in Rwanda: at present extraction rates, the lake could continue producing power for over 100 years. Gas is produced by extracting water from a depth of 260-270m. As it decompresses, the CH4 and CO2 come out of solution. The degassed water is then reinjected into the lake, near the chemocline. The CH4 and CO2 are separated by washing the gas in a stream of shallow lake water, extracted from a depth of 60-70m, at a pressure of about 6 atm. This water resorbs the CO2 and some H2S, and is then reinjected at a depth of 70-100m, while the CH4 remains as a gas and is transported to power plants on the lake shore. We plan to develop fundamental new understanding of the fate of the return water, both (A) injected deep in the lake, near the chemocline, to ensure minimal dilution of the methane rich deep water, and also (B) injected much shallower in the lake with the resorbed CO2, to ensure this does not degrade or stress the surface water ecosystem, especially the fish which are an important food resource. The research will involve running small-scale laboratory and theoretical models of the mixing produced by the plumes of reinjected water. This will enable accurate predictions of the evolving stratification and gas concentration in the lake over the next 50-75 years. We will use the models to explore different approaches for reinjection to identify the most effective approach. We will also develop new quantitative understanding of the risks and likelihood of a lake overturn event, leading to a major release of the dissolved gas, perhaps triggered by a fissure eruption of the nearby and active Nyiragongo Volcano. We will work with the University of Rwanda to build a cohort of students in Rwanda with specialist modelling capability on lake mixing; we will run workshops describing the research and demonstrating modelling tools which will emerge from the project, with KivuWatt and SPLK, as well as REMA the government environment agency and REG, which maintains and operates the energy infrastructure in Rwanda. This will help optimise the longevity of the power generation from Lake Kivu, minimise impact on the shallow lake ecosystem; and assess the evolving risks of a limnic eruption.  

UKRI Gateway to Research · FY 2026 · 2026-03

In the UK, almost all deaths and disabilities are caused by chronic diseases like cancer, diabetes and heart disease. These diseases are becoming more common, especially among people living in poorer circumstances, who tend to develop them earlier and experience more severe effects. People who are more physically active and eat healthier diets are less likely to develop chronic diseases. The way we live is influenced by personal choices and the environments in which we make them. For example, a tax-free bike scheme can make it easier to choose to cycle to work. Wealthier people often live in environments that support healthier lifestyles, which is one reason they are more likely to be active and eat well. Traditional ways of preventing chronic diseases focus on identifying people with the least healthy behaviours and helping them make healthier choices. While this does help some people, it is often less effective for people in poorer circumstances because it does nothing to address the root of the problem. To do that, we need to change environments in ways that make healthier choices easier for everyone, especially for those who most need help. There are many ways of changing the economic, physical and social conditions we live in, which makes it hard to know where we should focus our efforts. Our goal is to identify common characteristics of successful strategies that could be applied more widely to prevent chronic diseases related to diet and physical activity. To do this, we will: Revisit existing research. Instead of doing traditional systematic reviews we will examine previous studies through a new lens, focusing on how interventions work and what we can learn about where and for whom they work best. Instead of narrow questions like ‘Does taxing soft drinks reduce sugar consumption?’ we will ask broader questions like ‘Is raising the cost of less healthy foods an effective way to support healthier diets?’ Investigate what causes change. Many studies show a link between environment and behaviour, but they rarely show that one causes the other. For example, people living in neighbourhoods with more takeaway shops tend to eat more takeaway food, but that might be because they like takeaway food and choose to live in those areas. Using data from the UK and around the world, we will explore which environmental changes actually lead to increased physical activity, healthier diets and lower risk of disease over time Assess combinations of changes. We will assess whether certain combinations of environmental changes are more effective than single changes alone. For example, limiting advertising for less healthy foods might work better if healthier foods are also made cheaper. We will also explore the ways in which strategies work better in some places, or for some groups of people, than others. For example, congestion charging might be ineffective or unfair for people who work shifts and live in areas with poor public transport.  Our findings will be valuable to public health policymakers locally, nationally, and internationally. We have well-developed systems for sharing our insights with these decision-makers through written briefings, online platforms and in-person meetings. The methods we develop will also be useful for researching other health topics, so we will share them with experts in those fields and encourage them to develop them further.  

UKRI Gateway to Research · FY 2026 · 2026-03

The DiRAC Facility is submitting this proposal to request bridging funding of £6.1m to support continued Facility operations during FY26/27. This request represents minimal business as usual funding to “keep the lights on” at DiRAC, comprising: (i) technical and user support and electricity costs for the DiRAC compute services; (ii) the DiRAC Training Programme; (iii) the Research Software Engineering (RSE) Programme; (iv) on-going preparations for the DiRAC-4 services required to deliver the STFC Theory Programme beyond 2026; (v) day-to-day professional services support for the Facility. These bridging funds are also needed to enable the DiRAC Senior Management Team to continue their work with STFC and UKRI to define the UKRI Digital Research Infrastructure and establish the appropriate role for DiRAC within it. All current operations grants for the Facility end on 31st March 2026 and the requested funds are required to ensure that DiRAC services can continue to operate un-interrupted beyond this date. While the scale of compute services required to support the STFC Theory Community beyond 2026 is already established based on the DiRAC-4 science case, the timing of any hardware deployments is unknown. This bridging request is therefore based on the current compute services and activities that need to continue until at least March 2027.

UKRI Gateway to Research · FY 2026 · 2026-03

Biological function typically depends on proteins working together in teams. Routes for programming protein assembly should be specific and reliable in the context of many different proteins and cellular environments. Our group has generated a peptide called SpyTag and a protein called SpyCatcher (named after the bacterium S. pyogenes from which these parts were engineered). SpyTag/SpyCatcher technology has proven to be a powerful tool for bringing two proteins together simply, specifically and irreversibly. SpyTag technology has enabled diverse applications including in biomaterials, catalysis, cell therapy, structural biology and vaccines. SpyTag/SpyCatcher has been employed in bacteria, plants, mice, worms, flies, a range of livestock animals, and even in human clinical trials. Linking building-blocks irreversibly brings resilience over time and enhances the ability to monitor interactions in cells. We and others have now generated a set of Tag/Catcher pairs, harnessing the same idea of ligation through spontaneous covalent bond formation. However, these tools have low reaction speed, low ability as fusion partners and it is unknown whether the pairs are mutually specific and applicable in diverse cellular contexts. Here we will engineer a panel of Tag/Catcher pairs where each Tag or Catcher only reacts with its designated partner, ignoring other Tag/Catchers and other components of cells. This Tag/Catcher panel will provide a central underlying resource for the engineering of biology. This work will also establish fundamental insights into the computational design of split proteins for rapid reaction and cellular compatibility. Objective 1: Benchmarking the performance of the existing Tag/Catcher rainbow First we will quantify and compare key criteria for the large set of existing Tag/Catcher pairs, including reaction efficiency and selectivity. This objective will establish which pairs are best suited to take forwards to engineer for efficient building of molecular teams. Objective 2: Computational enhancement of Tag/Catcher pairing. Using a series of computational tools, we will design Tag/Catcher pairs with enhanced stability, reduced non-specific binding, and improved application in diverse cellular contexts. Objective 3: Directed evolution of rapid orthogonal Catcher toolbox. We will harness library selection to accelerate the reactivity, cellular display efficiency and selectivity. This objective will optimise Tag/Catcher pairs for selective and rapid reaction in a cellular context. Objective 4: Deep validation of optimised orthogonal Tag/Catcher pairs. Finally we will perform a complete characterisation of our optimised Tag/Catcher pairs, to demonstrate their applicability for the building of molecular teams in diverse cellular contexts. This objective will provide a thorough benchmarking, so that the Tag/Catcher panel can enable a new level of cellular programming and molecular assembly for the bioscience community. Rapid and selective multi-component coupling by this unique toolbox will have wide impact for both fundamental research and biotechnology. This proposal fits the BBSRC strategic challenge of “bioscience for sustainable agriculture and food”, given the wide use of Tag/Catcher pairs for assembly of vaccine candidates against diseases of farmed animals. This proposal fits BBSRC priorities of “understanding the rules of life” in investigating principles of split protein docking and isopeptide bond formation, and “transformative technologies” in the generation of a rapid and broadly applicable toolbox for molecular assembly.    

UKRI Gateway to Research · FY 2026 · 2026-03

How nervous systems organise and process signals to generate behaviour is a central question in neuroscience. The human brain consists of over 3 billion neurons which communicate via chemical neurotransmitters that turn partner neurons on or off with fast or slow dynamics. Traditionally it has been thought that complex behaviours arise as the size of the brain and number of neurons increases. However, animals with anatomically small networks, like the nematode worm C. elegans, nevertheless perform complex behaviours such as learning and maze navigation. Work by ourselves and others has uncovered a surprising level of complexity in neurotransmission in the worm nervous system which is achieved through an expanded set of neurotransmitter chemicals operating via a vast array of fast and slow receptors. One consequence is that excitatory ‘on’ and inhibitory ‘off’ signalling may be mediated by the same chemical neurotransmitter and even in the same neuron, a phenomenon not seen in mammalian nervous systems. We hypothesise that this expansion of signalling modalities represents a yet uncharacterised evolutionary strategy to generate complex behaviour. To address this hypothesis, we will focus on the use of dopamine in the C. elegans brain, which like in humans, is only released from a small number of neurons but has wide reaching effects on behaviour. However, unlike humans, worms have both fast and slow dopamine receptors and dopamine can act via both excitatory and inhibitory signalling. Making it a smaller more manageable example of this phenomenon of a physically small but complicated nervous system. First, we will build the first truly functional map of dopamine signalling in the worm brain by mapping the distribution of its receptors. This map will not only contain information about which neurons talk to each other but also whether these connections are excitatory or inhibitory, and if they act on fast or slow timescales. Using this map, we will then generate a computer model of the dopamine nervous system and make predictions of what happens to behaviour when we alter or challenge the system. By harnessing the power of this tiny worm, we can also characterise the behavioural importance of all components of the dopamine system as well as test our computer model predictions by carrying out behavioural analyses. By understanding how the small nervous system of the nematode worm can organise and harness opposing and complex signalling modalities we will be contributing to understanding the rules of life, not just those that govern humans but also those that underpin animals more broadly. We will also expand our knowledge of an important class of proteins that are currently used as major drug targets for anti-parasitic medicines, insecticides and for a range of medical applications including anti-psychotics and anaesthetics, which could pave the way for the development of novel therapies in the future. Discoveries made here will have impacts not only for people interested neuroscience and drug discovery, but this alternative strategy of having fewer neurons but doing more with each one could be a blueprint for designing more computationally efficient AI models. These investigations will address the fundamental question of how neurons manage a range of complex signalling patterns and pave the way for understanding these processes in larger animal brains.

UKRI Gateway to Research · FY 2026 · 2026-03

Around 30% of the eukaryotic proteome consists of proteins or protein regions that are disordered, but nevertheless have important functions. In biology, we have become accustomed to linking sequence to structure, and structure to function, but where there is no defined structure, we must think of the protein as adopting a dynamic ensemble of conformations. The paradigm therefore becomes sequence -> ensemble -> function, but studying protein ensembles can be very challenging experimentally, as they are heterogeneous and often invisible by diffraction methods or electron microscopy, and can suffer from severe peak overlap in NMR spectroscopy. Another issue is that the linear sequence of disordered regions is often not as well conserved over evolution as their global, physicochemical properties, making it difficult to track, understand and predict the sequence -> ensemble -> function relationships. Linker histones are abundant nuclear proteins that have a well-established function in the phenomenological sense: they, along with the core histones, bind and compact genomic DNA to make chromatin. Linker histones orchestrate a unique stage of this process: the condensation of the so-called 11nm fibre into a more compact structure, which reduces its transcriptional activity. The extreme endpoint of this process is a thicker, 30nm fibre, which has been observed in transcriptionally insert cells that use specialised linker histones. However, in transcriptionally active cells, the fibre appears more open, flexible and heterogeneous, somewhere in between the 11nm and 30nm fibre states in compaction level, and self-assembling into liquid-like globules. This “top-down” view, from super-resolution imaging, is resonant with our “bottom-up” findings, from NMR and molecular biophysics applied to a minimal in vitro model. Linker histones have a long, disordered C-terminus. We have established that this disorder is preserved when it binds short DNAs, explaining why its structure – termed a “fuzzy complex” ­– has defied the usual structural biology toolkits. We also discovered that these fuzzy complexes tend to coalesce into dense liquid condensates, which may explain how the dynamics of the 11nm fibre are retained in the liquid globules seen by microscopy. Linker histones therefore appear to function like a DNA “liquid glue”, and understanding exactly how the glue works will be an important step forward in chromatin biology.   Our aim is now to answer two overarching questions: Do minimal models of linker histone tails and short DNAs accurately recapitulate the region of interest in the context of full chromatin? What are the factors controlling linker histones in their role as DNA glues, and how are they coded by the protein sequence? These define our new objectives: To develop experimental models of full chromatin. To capture the local structure and dynamics at all stages of condensation. To measure the viscoelastic properties of the condensed chromatin fibre. To quantify the thermodynamics of condensation. To use the results of 2, 3 and 4 to establish the sequence -> ensemble -> function rules that encompass all linker histones. Achieving these objectives requires a fully joined-up approach of solution- and solid-state NMR, and new biophysical tools. This project is therefore not only about addressing a significant knowledge gap in chromatin biology by characterising a key disordered region, but an example of how integration of various methodologies can produce a picture of a disordered assembly that is far more informative than the individual techniques alone.

UKRI Gateway to Research · FY 2026 · 2026-03

Reaching net-zero greenhouse gas emissions by 2050 will require a 7-fold increase in the supply of critical metals. The demand for some critical metals, including lithium, is forecast to increase 50-fold over the next 25 years, outstripping production capacity by an order of magnitude. Without sufficient critical metal supplies the transition from fuel-intensive high-carbon to a mineral-intensive low-carbon economy will be impossible to sustain. Current critical metals production relies on energy-, water-, chemical-, and land-intensive processes, such as solvent extraction, ion exchange, and solar evaporation ponds. Membrane-based processes, including nanofiltration (NF) and electrodialysis (ED), can leverage selective transport to efficiently separate critical metal ions from brines; including salt lakes, geothermal brines, and battery and magnet recycling leachates; diversifying global critical metals production and securing the energy transition. With sufficiently selective membranes, NF and ED can drastically the energy, water, and chemical consumption of critical metals extraction and purification. By lowering the economic and environmental costs of production, membranes have the potential to delocalise and derisk critical metals supplies. Currently, membranes are used to separate ions in relatively low-salinity mixtures containing a small number of salts. Consequently, our understanding of membrane-based separations is limited to dilute mixtures of two or three different salts. However, industrially relevant critical-metal-containing brines are typically highly concentrated (i.e., containing more 100s of grams of salt per kilogram of water) and multi-ion (i.e., containing large numbers of salts). Designing membranes and processes to separate these complex, multi-ion mixtures is challenging because concentrated brines are thermodynamically highly nonideal. Furthermore, the number of potential ion combinations increases rapidly with the number of salts, making a trial-and-error experimental approach, where permeation tests must be performed for every possible brine composition for each new membrane, infeasible. This proposal aims to develop a mechanistic understanding of selective mass transfer in concentrated, multi-ion mixtures, enabling the rational design of membrane and processes for critical metals extraction and purification. First generalisable and predictive thermodynamic and mass transfer models will be developed for nonideal, multi-ion mixtures. Secondly, non-invasive, online nuclear magnetic resonance and terahertz spectroscopy combined with ion conductivity measurements will be used to probe chemical potential and diffusion in complex brines. Thirdly, physics-based multiscale models will be developed for selective transport in NF and ED, modelling mass transfer from the membrane scale to the boundary layer, membrane module, and system scales. The models developed through these three work packages will form the basis of an open-source computational framework for selective multi-ion transport in highly nonideal mixtures. By building a comprehensive understanding of the chemical thermodynamics and mass transfer that govern selective transport in complex brines, the proposed work will enable researchers globally to design new membranes and processes for drastically more efficient critical metal extraction and purification than currently possible. Beyond critical metals, a robust understanding of complex thermodynamic and transport phenomena in concentrated multi-ion mixtures will have broad applications across technologies vital to the clean energy transition, from flow batteries to fuel cells. Finally, the FLF will lay the foundations of a research group building models to enable the theory-guided design of membrane-based separations critical for the net-zero transition. The research program will train a new generation of chemical engineers in the cutting-edge skills needed to meet the challenges of a decarbonised minerals-intensive economy, helping to secure a sustainable clean energy transition.

UKRI Gateway to Research · FY 2026 · 2026-03

To what extent are Earth’s surface mechanisms biological phenomena? Processes such as water movement, sediment deposition and weathering are well understood from a physical and chemical perspective, but the landforms and landscapes that they generate were more than a passive stage-set in the theatre of evolution. Today the presence of plants and animals can modify and regulate surface processes and so the first organisms to colonize the land would have inhabited lifeless terrains unfamiliar to the modern eye. The activity of these organisms and their descendants, variably stabilizing the land surface, altering the propensity of weathering, and corralling and regulating waterways, would have terraformed Earth’s continents, generating new habitats and creating ecological opportunities and challenges throughout the evolving biosphere. Only by understanding the big picture effects of terrestrialization over geological timescales can we understand how unique Earth’s surface is amongst rocky planets and recognise the importance of plants and animals in shaping modern landscapes and ancient geological resources. Until now, however, several knowledge gaps have endured: uncertain timelines for terrestrialization persist due to a patchy body fossil record, the role of life in modern geomorphic processes is often underdetermined due to the finite historicity of instrumental records and problems of isolating specific causes, and teleconnections between evolutionary effects have been understudied. At the same time, a wealth of pertinent subsurface and outcrop geological evidence remains underutilized. We will resolve these problems and deliver evidence for the impacts of evolutionary terraforming on landscapes, evolutionary trajectories, and sedimentary geological phenomena, by utilizing recent theoretical and technological advances in which we have been heavily involved. The project will holistically interrogate multi-scale records of life-sediment interactions including the near-instantaneous modification of sediment grains, the life-span interactions between individual organisms and landforms, the centennial and longer interactions between communities and landscapes, the multi-millennial recycling of previously altered sediment, and the evolution of such phenomena over geological timescales. By focussing on the Silurian to Carboniferous interval, we will capture samples dating from the time of nascent plant and infaunal communities to that of well-developed forests and diverse burrowers. Stepwise stratigraphic variation in properties coeval with terrestrialization phase will be calibrated by analysing palaeoecological data relative to the timescales over which they accrued. Further, we will ascertain how evolutionary changes in marine settings were contingent on terraforming modifications in linked upstream settings. The case studies are selected primarily from the well-dated UK geological outcrop and subcrop record which is shown to be a globally exceptional record of Silurian-Carboniferous non-marine strata, but which has never been systematically interrogated within a modern framework considering bio-sedimentary influences and the time significance of strata. Our objectives are to establish a timeline of terraforming, shedding light on the mechanics of one of the most crucial episodes of Earth history, and to disentangle abiotic-biotic cause and effect relationships at multiple focal lengths. Meeting such objectives is essential to present-day predictions of the effects of vegetation introduction or removal on river morphodynamics, flooding and groundwater table, or how changes in terrigenous sediment flux can impact marine communities. An additional practical benefit of the research will be a better understanding of the evolution of regional subsurface stratal geometries through the UK Palaeozoic, shedding new light on potential targets for geothermal energy exploration, carbon capture, and deep geological waste disposal.

UKRI Gateway to Research · FY 2026 · 2026-02

Reconstructable Nano-Opto-Mechanical Metamaterials (ReNOMM) seeks to assemble nanoscale building blocks into 3D materials with optical, mechanical, and functional properties unlike anything found in nature, and at their end-of-life disassemble the building blocks for re-use. This project is uniquely placed to develop new paradigms for metamaterials, and create a larger, sustainable and more immediate impact for industrial applications. Metamaterials are a growing field within the UK, but to deliver a step change in our understanding of how to design, build and recycle these materials from end to end requires an interdisciplinary team across a wide set of fields. Metamaterials provide emergent properties by combining building blocks to elicit more than simple averaging over all component materials involved, instead giving exciting opportunities for new functionalities that are not found in natural materials. RENOMM is designed to push into a new set of opportunity spaces, and to form new productive collaborations. We do this by developing core projects that address the key challenge of designing and building 3D sub-micron metamaterials in a scalable way. A key novel aspect to be directly addressed in RENOMM is the incorporation of mechanical bistability and nonlinearities, which has not yet been realised at sub-micron sizes. This exploits switching phenomena previously developed at the macroscale, but now integrated into metamaterial architectures to provide radically new unusual properties such as energy absorption and harvesting, mechanical intelligence, enhanced sensors, anti-fouling protection and more. Incorporating these meta-mechanical properties yields novel optical, thermal, sensing, photochemical, and other functionalities. Using a demonstrator approach, aided by specifications from industry partners, we focus on more technically viable solutions for metamaterials, driving this field and giving the optimum outcome for UK translation, as well as building an expert array of users and diverse use cases.

UKRI Gateway to Research · FY 2026 · 2026-02

Aim The ability to use memory to discriminate objects and react accordingly is fundamental to human behaviour but is often disrupted in clinical conditions like dementia. Upon seeing an object, we perceive its appearance, evaluate its familiarity, and recall its name, functions, and past interaction. With memory, we can discriminate familiar objects better than novel objects. Previous studies elucidated how visual objects are identified, memorised, and recalled. However, how object memory is ‘used’ to influence behaviour remains poorly understood. Uncovering its mechanisms will greatly advance our understanding of visual cognition and its disorders. I aim to determine the neural circuits involved in using object memory.   Transformative Objective In perception and memory of visual objects, a brain area called perirhinal cortex plays essential roles. I pioneered an optical approach to cognitive neuroscience, where we used light-gated proteins to control genetically-targeted neurons by light during a cognitive task. I discovered that optically activating object memory neurons in the perirhinal cortex caused the animals to judge any presented object as “familiar” even when novel. This finding of a memory signal within the perirhinal cortex has opened a new possibility for studying neuronal circuits by which object memory is used in visual cognitive decision-making. We can ask: What information does the perirhinal cortex signal to which parts of the brain? Which signal pathway contributes to what aspect of visual cognition? I hypothesise that one pathway to frontal cortex guides cognitive appraisal of an object, while another pathway to visual cortex improves its perceptual discrimination. My objective is therefore to determine if separable projection pathways from the perirhinal cortex impact differentially to cognitive and perceptual judgements about objects.   Innovative Approach To study such circuit-specific functions, I have advanced optical techniques and further focused on a novel model species. They can see objects sharply and perform complex cognitive tasks. Their highly evolved but compact brain allows robust viral vector expression and easy access to most cortical areas, making them ideal for the optical approach. Their small body and efficient reproduction enable socially-enriched group housing, use of large numbers required for linking circuit and behaviour, and the creation of genetically-engineered strains and psychiatric and neurodegenerative disease models including dementia. A significant international trend is therefore growing towards this next-generation animal model to study higher cognitive functions and dysfunctions. I will first train these animals in two tasks for cognitive (familiar versus novel) and perceptual (same versus different) discriminations of objects. Next, I will localise memory neurons in the perirhinal cortex by electrical recording, and then map their activity propagation pathways by their optical activation and whole-brain imaging. Then, I will optically activate and inactivate those pathways during the tasks, and distinguish which pathway is critical for cognitive or perceptual discriminations. My institute has the best possible facility and community for this project.   Impacts I will develop a cutting-edge paradigm and dissect visual cognitive decision-making into distinct circuits crucial for perceptual and cognitive components, which is unreachable by existing paradigms. My project lays the groundwork to study detailed circuit-processing mechanisms for visual cognition and understand circuit-impairments in visual cognition disorders through applying my paradigm to the disease models as well as investigating homologous circuits in humans. This project will significantly advance cognitive neuroscience and brain health, allowing me to lead the paradigm shift to ‘circuit physiology of cognition’.    

UKRI Gateway to Research · FY 2026 · 2026-02

Mental health conditions are common and have a huge impact on people’s quality of life and on the economy. For many patients, successful treatment remains difficult to find. We know from genetic studies that genes, cells and molecules are important in causing symptoms, but there are no personalised treatments available for patients based on measurements of these ‘biomarkers’. While many studies are now trying to address this by measuring these biomarkers in large groups of people, the data often remain inaccessible to patients, researchers and industry, unless they have gone through lengthy application processes to access this information. This makes it slower to develop successful new treatments (only 20 new FDA-approved mental health drugs in the last decade). We want to connect together, safely, data that is currently hidden away. The Open Psychiatry Project will make a website displaying interactive summaries of the results of many studies of genes and biomarkers in mental health, without the privacy risks involved in data about individuals. This will be the first time that multiple real-world biomarker datasets are brought together in an open, accessible way. We will also test ways to allow researchers and patients to ask their own questions about these datasets in a way that does not allow users to see the personal data on individuals - this technology is called ‘privacy-preserving data federation’. Federation means a way of looking at information which is stored in different places all together - making it quicker and easier to work with it, and helping ensure there are enough samples from under-represented groups for the results to be meaningful for everyone. By doing this, we hope that UK data on genes, molecules and mental health can improve our understanding of mental health in different groups, and lead to new treatments. By providing this infrastructure to users, we aim to speed up the science, commercial development and patient involvement that will help health professionals to take an individualised approach to treatments in the future, where blood tests could be used to help determine which treatments are likely to benefit you personally. We want industry to be able to access this data to help them develop new treatments for patients. The public are concerned about this, so we will ask them to help us make sure this is done in an ethical and transparent way. Industry will not have access to personal information on individuals, only data summaries. Patients from across the UK have co-developed these plans, and will partner with us throughout the project. A diverse group of adults and young people with lived experience and understanding of how to make information more accessible will co-develop the website and resource. They will work alongside academic researchers, software engineers and data specialists. All team members will work to explain our progress and promote the use of our resources by patients and the public, as well as by academic and industry users. We will also support patients to work with the data to answer questions that are important to them.

UKRI Gateway to Research · FY 2026 · 2026-02

Pregnancy is a unique state during which nearly every organ and tissue in the mother’s body adapts to support fetal development. Whilst some changes reverse after delivery, pregnancy often leaves causing permanent changes in the female body, a phenomenon observed across mammals. Proper regulation of these adaptations is essential, as their disruption can lead to pregnancy complications that pose immediate and long-term health risks for both mother and offspring. These risks extend beyond women and their families, affecting animal health, productivity and the economic stability of livestock industry and food production. Despite these far-reaching implications, pregnancy remains under-researched, particularly in the context of healthy aging in females.   The placenta, a vital organ for fetal development, secretes signalling factors, including hormones, believed to drive adaptations in the mother’s body during pregnancy. However, until recently, models and tools to pinpoint the role of placental hormones in these processes have been lacking. We also have limited understanding of how these hormones contribute to long-term health maternal health risks after pregnancy. To address these gaps, we developed a genetically modified mouse model in which placental hormone production is specifically disrupted during pregnancy. Preliminary studies show that this disruption alters in maternal metabolism both during and after pregnancy. Consequently, we can now study the mechanisms by which placental hormones influence maternal health during pregnancy and aging, forming the basis of this grant.   By combing this advanced mouse model with rigorous metabolic testing, imaging and tissue assessments, this project will examine in detail how placental hormone production affects health of the mother during pregnancy and with aging after pregnancy. Using highly-sensitive profiling techniques, we will measure when placental hormone levels change during pregnancy and link these patterns to alterations in maternal metabolism. Targeted experiments will determine the specific functions of individual placental hormones in driving these changes. Finally, we will using cutting-edge DNA and gene sequencing will reveal the pathways through which placental hormones create lasting “memories” in maternal tissues and organs, influencing metabolic health long after pregnancy.   Through an integrated, systematic approach and advanced tools, we will uncover the fundamental links between placental hormones and animal physiology. Our research will identify the timing and molecular mechanisms involved, shedding light on how placental hormones function to shape female health during pregnancy and beyond. These insights will help explain differences in health and lifespan between females and males, and clarify how pregnancy complications arise, providing a foundation for better health policies and advocacy for women’s health monitoring during and after pregnancy. Our findings may also have implications for those in the farming/agricultural sector and the development of strategies to improve the health, productivity and fertility of livestock. Researchers and students involved in this project will gain expertise in animal physiology, tissue analyses, molecular techniques and big data. Data generated will benefit diverse fields, including reproduction, development, pregnancy, women’s health, ageing, genetics, metabolism, and health across generations. We will share findings through institutional seminars, local outreach, and conferences attended by biologists, clinical doctors, and stakeholders across industry, academia and government. Public engagement efforts, including science festivals and school visits, will maximize societal impact and inspire the next generation of scientists. This proposal addresses directly BBSRC Responsive Mode Priorities to understand Animal health, the Rules of life and Healthy aging across the lifespan.

UKRI Gateway to Research · FY 2026 · 2026-02

Context: Recent technological developments in the fields of data acquisition and data processing (computer graphics and knowledge representation) open up exciting possibilities for object-oriented disciplines, in particular the history of art and architecture. The drive to reconstruct historic contexts has accelerated with accessible rendering programmes and powerful computer graphics. However, without embedded and transparent metadata and paradata, 3D-models still lack credibility as valid research outputs alongside conventional peer-reviewed articles and books. While widely recognized, the transformational potential of 3D modelling and visualisation tools for humanities research is thus rarely realised. Challenges: Present work is held back by unresolved issues of documentation, traceability (validation), interoperability, accessibility and long-term availability. Isolated projects with limited lifespans discourage engagement from humanities researchers. Current trajectories show these trends persisting and deepening, with 3D for Cultural Heritage focused on documentation, divorced from humanities research. Practice falls far short of recommended scientific practice, fostering negative and persistent perceptions amongst humanities scholars of 3D models as an ‘unserious’ field. It has been clear for some time that negotiating this impasse will require digital practitioners in AAH to move beyond historic reconstruction and superficial visualization, to engage in sustained discussion with architectural engineers and data scientists around technical standards and platforms. Aims and Objectives: Serious 3D in Art and Architectural History aims to overcome this stubborn disconnect between potential and practice with an innovative approach, drawing on established collaborative and interoperable technologies from civil engineering cross-referenced with Linked Open Data Resources. We demonstrate proof of concept with a building-scale model of an iconic art historical monument, the Palazzo Medici (Medici palace) in Florence. This case study – with excellent documentation, exceptionally rich scholarly literature, and a diaspora of major artworks commissioned for its interior – will demonstrate how a HBIM 3D-model can provide an open research environment for a highly complex monument, capturing its chronological stratification, relevant historic sources, dispersed contents, and diverse (often conflicting) scholarly analyses with their attendant uncertainties. An interdisciplinary team of art and architectural historians, engineers and data scientists will investigate the requirements for data acquisition, data processing, data publication and storage using the example of the Palazzo Medici in Florence. Using this tangible example of a Renaissance building containing extensive material for research in art and architecture history, the project seeks to test the extent to which the tools for complex and interdisciplinary planning and documentation of construction and operation processes can be applied to humanities research; re-thinking approaches to object-oriented research, interpretation, dissemination and access to the knowledge (publication). Potential Applications and Benefits: Of central importance is the development and evaluation of a research methodology based on normative structuring, object-oriented 3D modelling, and role-/model-based communication using established standards Building Information Modeling (EN ISO 19650-1:2018), establishing a best practice paradigm which will be applicable and scalable across the discipline. By linking objects with further relevant Linked Open Data resources beyond the structured data model of the 3D model, the model enables further contextualisation of the model in regard to the FAIR principles. Opportunities for publication and long-term archiving of the generated digital research data will be explored and exploited, incorporating existing and emerging infrastructure systems and services of engaged partners and supporting institutions and initiatives.