University of Cambridge

UKRI Gateway to Research · FY 2024 · 2024-09

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

UKRI Gateway to Research · FY 2024 · 2024-09

A bird's-eye point of view of the central objectives of this grant are: 1. To use the language of tensor networks to synthesize the mathematical structures obtained in the context of integrable spin systems, conformal field theory, topological field theory and tensor categories, and to use that characterization to study topological and/or critical phases of matter. 2. To develop a powerful variational tensor network toolbox incorporating non-local / categorical / non-invertible symmetries, unravel the entanglement structure of different phases of quantum many body systems, both for the case of lattice systems and of quantum field theories. 3. To use this toolbox to construct state of the art renormalization group flows for interacting systems, both on the lattice and in the continuum. 4. To use tensor networks to construct and analyse novel quantum error correcting codes, and study the relationship between error correction, entanglement, the holographic principle and renormalization.

UKRI Gateway to Research · FY 2024 · 2024-09

GNSS-R is a technique to carry out Earth observation based on reflections on the ground (or sea, or ice) of signals originating from GNSS (Global Navigation Satellite System) signals. The proposed project consists of educating a new generation of experts, at doctoral level, able to bring a qualitative leap to this technology. The scientific and technological goal consists of developing such systems based on a synchronized constellation of Cubesats. An important advantage of this arrangement is the very low cost of cubesats and the possibility to increase resolution based on beamforming from the satellites. Ground truth, as well as some of the methods, will originate from near-field radar technology. This will require further research on all segments of GNSS-R technology and beyond: launching and adjustment of cubesat formations, RF synchronization, interferometry between moving platforms, calibration of RF front-ends, ground testing making use of drones, cubesat systems, on-board processing, data transfer and analysis, translation into ground truth and into predictions important for climate change studies and for optimal territory management. The project may also benefit to other technologies making use of interferometry, such as radio-astronomy and phased array based communications. It is also expected to assist industry segments making use of GNSS signals, such as precision agriculture, forestry and sea and land management.

UKRI Gateway to Research · FY 2024 · 2024-09

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

UKRI Gateway to Research · FY 2024 · 2024-09

Our Universe is expanding faster than we expected. The standard model of cosmology predicts a Hubble constant which differs substantially from what we measure it to be. Far from being a problem, this is exciting as it indicates the need for a new model of the Universe. Despite three years of effort however, cosmologists have been unable to resolve this cosmic conundrum. The reasons for this community failure are threefold. First, no single theoretical solution is capable of satisfactorily resolving all discrepancies. Second, disentangling new physics from measurement error is a challenging unsolved problem. Third, our simulation and data analysis pipelines have been designed and tuned in the context of the standard model, which can bias even the most carefully designed approach. This ambitious project proposes to resolve all three of the above and uncover and establish the next cosmological paradigm for theory and data analysis. An interlocking programme of theory, inference and observational research, undertaken by the PI, three postdocs and four PhD students over five years will aim to simultaneously resolve the tensions in both cosmological theories and data processing. The broad aims of the project are to (a) Resolve the tensions between cosmological observations with a new standard model of the universe and next-generation numerical techniques (b) Establish likelihood-free inference at the heart of our cosmological analysis toolkit in preparation for the future onslaught of big cosmological data, and (c) Bring together a diverse set of cosmological and particle physics datasets and organise them in a coherent statistical framework. This is an essential and substantial research effort which only an ERC starting grant can support.

UKRI Gateway to Research · FY 2024 · 2024-09

The principal aim of this Fellowship will be linked to building an academic publication track record, for which I will commit 60% of the time. Firstly, I will work on a monograph based on my PhD thesis, and aim to produce a first draft of the manuscript within the first three months, from October to December 2024. The book will contribute to the historiography on the Cold War and summitry, by bringing to the fore a new perspective, arguing that a triangular relationship between Romania on the one hand, and the US and the UK on the other, existed from 1974-1980. I will submit the draft to the publisher (potentially Oxford University Press), and then work on revisions throughout 2025, with the aim to deliver the final book manuscript by October 2025. Secondly, I will write an article about the Anglo-American allies' collaboration with Romania on areas such as the Middle East, with the aim to submit to the Cold War History journal in August 2025. Limited research I will use 10% of the Fellowship's time frame for archival research, and will aim to collect US, UK, and Romanian material mostly in digital form, but I will also pay short stay, in person, research visits to archives in London and Cambridge. All such material will enrich the answers of my PhD research questions, and help develop my project further (in line with my PhD examiners' recommendation) Research engagement, networking, and social impact I will dedicate 15% of the time to academic and non-academic research dissemination, as well as to networking, and social impact. I will be disseminating my research findings through a paper delivered at the International History Seminar held by the Institute of Historical Research in London. Moreover, I will contact the Romanian Cultural Centre in London, which would also be an ideal place for disseminating my research findings, as this is in close contact with institutions such as the Romanian embassy. Additionally, I will approach policy-making institutions, such as the Woodrow Wilson Center in Washington D.C. and Chatham House in London, as part of my plan to build pathways to policy impact. At Cambridge, I will organise a workshop that will bring together researchers, policy-makers, and diplomats with interests in diplomacy, summitry, and trade during the Cold War, with a focus on Eastern Europe. The workshop will advance cutting edge and interdisciplinary debates regarding East-West co-operation via summitry and trade during the Cold War. The event's output will take form of a briefing note summarising key discussion points and reflexive feedback from the participants. Additionally, I will seek to build contacts with the Centre for Geopolitics in order to broaden my interdisciplinary academic networks. Developing research and funding proposals I will commit 15% of the Fellowship's time frame to laying the groundwork for future research projects and building my networks. I plan to carry out future postdoctoral research based on my PhD and archival visits to US, UK, and Romanian institutions, in order to investigate the triangular relationship's revival after 1990, as well as East-West co-operation and the role of summitry and trade in achieving geopolitical goals during the Cold War. I will apply for postdoctoral funding at the British Academy, Leverhulme Trust, and Horizon Europe.

UKRI Gateway to Research · FY 2024 · 2024-09

Recent years have seen a vast surge in the volume and sensitivity of data being generated and collected, e.g., in genetic sequencing, distributed storage services, and graphs of social networks. The ubiquity and sheer size of modern datasets raise an urgent need to develop new techniques and methodologies for scalable computation. At the same time, the rise of blockchain technology, which underlies deployed distributed systems such as Bitcoin and Ethereum, provides ample motivation for developing decentralised protocols that could go beyond challenging centralised financial control and profoundly impact society by providing a foundation for real-world distributed systems that can be used for public benefit. A critical paradigm for meeting the challenges imposed by both of the desiderata above is that of verifiable computing. Here, the goal is to allow verification of computation performed by a strong third party (e.g., the cloud or a quantum computer) in a scalable, secure, and privacy-preserving way. Moreover, with the advent of quantum computing on the horizon, it is imperative that the verification would also be post-quantum secure. This proposal is focused on pushing the boundaries of classical and quantum verifiable computing and its real-world applications to delegation of computation to the cloud and blockchain technology. The proposed approach is inherently interdisciplinary, traversing computer science, mathematics, and quantum physics. The project involves strong national and international collaboration both in academia and industry. Its primary objective is to resolve long-standing open problems in the field, make an industrial impact by revolutionising how we delegate computation, and significantly increase the UK's capability of meeting the societal needs of preserving privacy and decentralising society in an upcoming quantum world.

UKRI Gateway to Research · FY 2024 · 2024-09

Traditional array seismology, where networks of 10s of broadband seismometers are deployed to record earthquakes and ambient noise, has long been a strength of UK geophysics. It has played a major role in constraining the structure and processes that define our planet from the crust through to the core. However, over the last decade, a new low-power, compact, self-contained and cheap seismometer - the seismic node - has heralded a step-change in capability. Nodes can be deployed in their thousands, in so-called large-N arrays, to record the seismic wavefield at unprecedented resolution. However, to date they are simply not available to the UK science community, except via potentially expensive ad hoc loans. The new technology can facilitate many projects, traditional and new, closely aligned with NERC's remit. This includes monitoring and imaging of geothermal systems and carbon capture and storage sites; detailed investigation and hazard assessment of landslides, earthquakes and volcanoes; and measurement of ice sheet flow and deformation in the context of climate change. The equipment will be based at the University of Cambridge, which has dedicated technical staff, laboratory and storage space for broadband seismometers, thus allowing nodes to be provided at no cost to the UK community. The operation of the pool will be the responsibility of the Management Committee, which will be made up of the project partners, the project lead and all seven co-leads who have proposed projects across the NERC remit. These experiments include environmental and urban seismology, cryosphere studies, energy transition research, and earthquake and volcano monitoring. The project is timely, given the rapid uptake of large-N seismology around the world, and the complete absence of a node pool that is open to the UK community. Once the project is completed, the nodes will become part of NERC's GEF facility, which has a robust and proven system in place to ensure access by a wide range of users. While expanding scientific capability within NERC's remit, the seismic node pool will also enhance sustainability across the UK seismology community. Compared to traditional broadband seismology, nodes are extremely compact, deployable by foot or low power transport in significant numbers (10s to even 100s), and require virtually no consumables in the field. They have a lifetime in excess of 10 years and their parts are subject to recycling and reuse. As a result, large experiments can have a minimal environmental impact. Furthermore, their low cost and ease of use ensures equitable access, with cutting-edge experiments possible with limited funds. This is further enhanced by the minimal technical expertise needed to operate them, and the delivery of the complete archived dataset once the nodes are returned to base. In summary, this community driven proposal to provide access to a pool of seismic nodes will allow the UK geophysics community to maintain its place at the forefront of passive seismology. It provides a more sustainable option compared to current equipment, with ease of use and low cost allowing new users to take advantage of seismic data. The link to NERC GEF ensures that the equipment will be used well beyond the duration of this grant. Most importantly, it will both enhance traditional strengths of UK geophysics (tectonics, volcanology, earthquakes) and allow seismology to contribute to other areas across the NERC remit (cryosphere, environmental science, energy and resources).

UKRI Gateway to Research · FY 2024 · 2024-09

The generation of novel therapeutics often depends on improved tools to bridge and combine biological building-blocks. We have developed a simple and efficient route to link peptides and proteins in living systems, a kind of protein superglue. This route depends on a surface protein originally derived from the bacterium Streptococcus pyogenes. This superglue technology has reached the clinic for vaccines and is moving towards the clinic for anti-cancer therapeutics. However, most of the world experiences mild infection by this bacterium and generates antibodies that recognise the bacterium's surface proteins. Such an immune response is a major obstacle to the success of this protein superglue for new therapies. Here we will develop variants of our protein superglue that are minimally recognised by the human immune system. We will then make use of our re-engineered superglue towards an important challenge for cell-based therapies. CAR-T cells have become a highly successful therapy for cancers of B cells. However, CAR-T cell therapy has not been successful against cancers of T cells. We will apply our protein superglue to address limiting factors for CAR-T cells against T cell cancers. We will establish control over the extent and time-course of CAR-T cell activation against T cell lymphoma cells, which is important to avoid sometimes fatal immune over-activation. Using the re-engineered superglue, we will also establish the efficient targeting of the CAR-T cells against cell-surface markers that are specific to the cancer and not all T cells, which is key for avoiding dangerous immunodeficiency.

UKRI Gateway to Research · FY 2024 · 2024-09

Despite conservation and management efforts, global biodiversity continues to decline due to climate change and growing human impact. Existing biodiversity management frameworks are limited by a lack of robust baseline data and a narrow focus on short-term ecological observations, potentially leading to flawed long-term outcomes. Terrestrial ecosystems require centuries to millennia to respond to external forces, highlighting the need for long-term datasets. Also, many current management approaches are rooted in colonialism and overlook Indigenous people's expertise and long-term connections to nature. The concept of wilderness, for instance, has excluded Indigenous stewardship from landscapes, resulting in negative consequences in various ecosystems. Incorporating Indigenous knowledge and understanding their historical land management practices is crucial for effective biodiversity management and cultural security. Additionally, it is crucial to address the current gap between long-term ecological (palaeoecological) studies and on-ground management actions. One of the primary reasons land managers predominantly rely on present (short-term) ecology rather than palaeoecology as the foundation for management is the historical focus of the interpretation of existing palaeoecological records. Bridging this gap requires a contextual design and interpretation of palaeoecological studies for the purpose of ecosystem management. Project IPPET aims to integrate local/Indigenous perspectives and past and present ecological methods to establish robust palaeoecological baseline knowledge to refine current management strategies, as well as bridge the gap between palaeoecological research and on-ground management practices by working closely with land managers. The project will focus on wetland ecosystems, including understudied areas like The Great Fen in the UK, Ramsar sites on Alderney and Island, King Island in Australia, as well as coastal wetlands in southern Nigeria and Principe Island. Wetlands are vital for carbon storage, habitat provision, freshwater quality, and flood mitigation, but they face threats from climate change and human impact. Project IPPET will generate a detailed palaeoecological dataset of long-term wetland dynamics in these regions, combining different lines of evidence, including proxies, surveys, existing data, and Indigenous perspectives, providing the understand of the complex interactions between wetland ecosystems, surrounding vegetation communities, climate, fire, sea-level change, and human activities in recent and ancient times. The outcomes will inform the protection of threatened and endangered species, detect undesirable ecological outcomes associated with existing management actions, and provide recommendations to refine management frameworks. These diverse wetland types (freshwater and coastal) across different climates (temperate and tropical) captured in this project will also help us to understand the role of climate heterogeneity in global wetland development.

UKRI Gateway to Research · FY 2024 · 2024-09

Cell therapy with T cells expressing gene-engineered chimeric antigen receptors (CAR) specific for cancer-associated antigens is transforming the way we treat patients with blood cancers, including myeloma. A critical issue limiting efficacy of cell therapies is that durable responses are limited by poor maintenance and survival of transferred cells resulting in treatment failure and myeloma relapse. There is a need to develop methods to enhance the persistence of CAR T cells for development of therapeutic products with long-lived efficacy. Long-term maintenance of T cell responses is dependent upon maintaining a pool of stem cell-like memory/progenitor T cells which are long-lived and self-renew, but do not engage in effector functions. Our prior BBSRC-funded work has revealed that the transcription factor BACH2 is required for the differentiation of long-lived stem/memory CD8+ T cells. However, conventional high-level overexpression of BACH2 locks T cells in a stem/memory differentiation state unable to engage in effector functions and mediate anti-tumour responses in vivo. To surmount this issue, we have recently developed an approach to deliver dose-adjusted expression of BACH2 at low levels to tumour-reactive T cells, which enhances stem/memory differentiation without compromising effector function. We find that dosed expression of BACH2 to tumour-reactive T cells results in marked improvements to persistence, efficacy and function in murine pre-clinical cell therapy models. With this proposal, we aim to configure dose-optimised BACH2 delivery for deployment in CAR T cell therapy of multiple myeloma using a novel CAR targeting SEMA4A, to optimise quiescence factor dosage for optimal function of anti-SEMA4A CAR T cells in vivo, and to test the safety and efficacy of the new product in widely established pre-clinical models of multiple myeloma. Our proposed work is organised into three Aims: Aim 1. Defining the optimal dose for quiescence factor delivery in anti-SEMA4A targeting CAR T cells Aim 2. Defining efficacy and toxicity of BACH2 dose-optimised SEMA4A CAR T cell therapy in murine pre-clinical multiple myeloma models Aim 3. Development, pre-clinical efficacy and safety evaluation of a lentiviral vector system for dosed quiescence factor co-delivery with CARs into human T cells Follow-on funding will be a critical step in translating our BBSRC-funded discoveries through commercialisation of this technology for the benefit of patients and society.

UKRI Gateway to Research · FY 2024 · 2024-09

A Chinese-financed $15 billion dollar port city project is dramatically restructuring today's Colombo. Yet, Colombo has a deeply layered imperial past: it was initially a Muslim settlement, before it came under a succession of European empires, Portuguese (first trading post in 1518), Dutch (1656-1796) and British (1796-1948). This project interrogates how these outsiders made a city in an unstable environment at the centre of the Indian Ocean, in which arose a diverse society, generating an abundance of cultural production and a sequence of violent politics. The four pathways of research: 1) In environmental terms, this multiply- colonised and repeatedly-engineered city is built in a wetland without a significant natural harbour; 2) In social terms, in a heavily nationalised state, the city has resisted indigeneity, as it is inhabited by many minority communities with long narrations of origin; 3) As for culture, Colombo was represented in keeping with recurrent motifs, as a site of transit across the Indian Ocean, including for enslaved and indentured labour as well as settlers; 4) And on politics, the heavy work needed, at the bridge of sea and land, gave rise to urban violence between communities in the midst of civil war; sustained strikes and new political movements, even in the months prior to this submission. For all these reasons, Colombo's past is a mirror to the legacies of enslavement, empires, postcolonial conflict and inequality; the long history of global Islam; the rise of China at the doorstep of India; and the environmental crisis. To critique these relations of pasts and presents, the project will bring artists together with historians and develop an open- access platform which works towards a more inclusive future. By decentring global North narratives of diffusion, global South narratives forged out of nationalism, and narrow accounts of empire, port cities or bonded labour, this will be a transformative exemplar of research on and for cities.

UKRI Gateway to Research · FY 2024 · 2024-09

Many pedagogic innovations and teacher professional development programmes fail to translate into change in actual classroom practice, leading to significant waste and missed opportunities to achieve more equitable learning. We know simply getting started and trying new approaches is critical, yet challenging and risky. Many interventions fail during this initial step. Common constraints to educational change are well-known, but we know far less about how and why teachers overcome such constraints to take the first 'leap of faith' and trial new pedagogic approaches. This gap in knowledge is especially notable in Southern Africa where pedagogic change efforts have proliferated for decades with little effects on classroom practice, stymying efforts to achieve equitable learning globally. My doctoral research addressed this gap by examining 15 teacher professional development and pedagogic change initiatives in Southern Africa, and asking how, why, and under what conditions do teachers trial new pedagogic approaches? The research broke methodological ground by designing a new theory-based approach to sampling, comparing, re-analysing, and synthesising existing evidence from peer-reviewed publications. Each selected change initiative had documented evidence of (a) teachers trying new pedagogic approaches and (b) the learning processes and conditions that supported teachers to try new approaches. Detailed re-analysis and cross-case comparison made it possible to develop original theory about the unique combinations of professional learning processes and local conditions that enable teachers to initiate pedagogic change. A follow-up 'live' case study tested and refined this original theory by drawing on teacher experiences in an ongoing pedagogic change initiative being scaled nationally in Botswana. Findings from both phases of research revealed starting pedagogic change does not require perfectly enabling conditions. Focusing on a few key processes like ensuring teachers feel supported, are practically prepared and have a bit of positive pressure (i.e., shared expectations for change) can be enough to enable initial trials. Achieving more significant pedagogic shifts requires (a) ongoing learning and (b) supporting teachers to reimagine what they see as pedagogically possible in their classrooms. Both can be achieved by offering teachers structured time to discuss, reflect upon and make sense of initial trials. These findings have vital implications for educational change efforts in Southern Africa and beyond. This fellowship will allow me to consolidate findings into user-friendly outputs that I will then share with researchers, practitioners, and policymakers in workshops, seminars, and conferences. The fellowship will also enable me to build upon the novel methods and theory developed during my doctoral research to maximise research impact and establish foundations for an interdisciplinary academic research career in professional learning, transformation, and innovative methods. I will work with mentors in Cambridge's Faculty of Education and Department of Land Economy to concretise interdisciplinary research connections I am already establishing. We are currently testing if findings from my PhD research apply in other professional settings, like homelessness prevention. This study and my PhD work are creating a cumulative evidence base of cross-profession learning and change mechanisms, which can inform and support future efforts for sustainable living and learning. During the fellowship, I will conduct several expert practitioner interviews to provide feedback on this cumulative evidence base, and to generate stakeholder perspectives which can inform future cross-profession research proposals. I will also draw on support from both departments to develop cross-profession and -disciplinary networks and identify potential collaborators for future research proposals.

UKRI Gateway to Research · FY 2024 · 2024-09

Poor placental development during the first-trimester of pregnancy can result in fetal growth restriction (FGR), a condition in which a fetus is unable to achieve its genetically determined size. The placenta's functional capacity depends on the coordination between the placental cells called trophoblast stem cells (TSCs) self-renewing (i.e., increasing in number) and differentiating (i.e., transforming) into specialised cell-types. This process is regulated by coordinated changes in sets of genes. Activating these genes require access to DNA regions that is achieved by 'epigenetic' modifications to the DNA. One form of epigenetic regulation (referred to as DNA methylation) is the addition of methyl groups that commonly results in switching off gene expression. The inverse of this is DNA demethylation which removes methyl groups leading to gene activation. Compared to all other tissues, the placenta exhibits low levels of DNA methylation, particularly in early pregnancy as it is believed to be critical for trophoblast development. However, little is known about how DNA demethylation (i.e. methl-group removal) is regulated in the human placenta during this critical stage of pregnancy. Nutrition plays a vital role during early placental development as both animal and human studies show that diets low in micronutrients such as Vitamin C (VitC) during periconceptional periods (i.e., before conception to early pregnancy) result in decreased placental and fetal growth. This proposal seeks to understand the role of VitC in regulating trophoblast stemness (i.e., the ability of TSCs to self-renew and differentiate). Our preliminary data shows that VitC promotes DNA demethylation and trophoblast stemness at concentrations 100-fold lower than those required to reduce reactive oxygen species (harmful by-products of metabolism). Moreover, VitC exhibits a J-shaped relationship on trophoblast growth with inhibitory effects observed at very low or high levels. Lastly, both low levels of VitC in maternal blood and reduced levels of the placental vitamin C transporter mRNA were associated with FGR. Our central hypothesis is that physiological VitC concentrations (i.e., concentrations obtained from healthy diets) promote trophoblast self-renewal by DNA demethylation of stemness genes. We will first determine the mechanism by which VitC regulates stemness in human TSCs and establish the optimal dose. We will then determine the effects of the optimal VitC dose on DNA (de)methylation and activation of genes regulating TSC growth. Lastly, we will use existing maternal blood and placental samples from a prospective pregnancy cohort to evaluate if low maternal and placental VitC levels are associated with reduced placental DNA demethylation and increased risk of placenta-related pregnancy complications. While the objectives of this study are to understand how VitC regulates trophoblast stemness, the study's findings may also have profound public health implications. For example, they may lead to optimal dosing strategies for VitC supplementation during the periconceptional period to reduce the risk of placenta-related complications. They may also explain why previous clinical trials of supplementation with high (supraphysiological) doses of VitC during mid-pregnancy in women at risk of pregnancy disorders have failed to prevent adverse events.

UKRI Gateway to Research · FY 2024 · 2024-09

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

UKRI Gateway to Research · FY 2024 · 2024-09

Biological-material hybrid systems are increasingly important in medicine, biotechnology and energy. In particular, microbial biohybrids offer unique advantages for sustainable energy conversion (e.g. scalability and product versatility), but their under-performances curtail their application and impact. State-of-the-art approaches to biohybrid research are slow and confined, with many hidden antagonistic interactions at the bio-material interface to overcome. Here, I aim to create a ground-breaking approach that directly targets the creation, identification, and characterisation of synergistic microbial-material interactions to enable a step-change in generating green energy biohybrids that are high-performing, robust and scalable. Towards this, I will i) develop new methodologies to generate large targeted libraries of key biohybrid components (the electrode, cells and charge carriers); ii) pioneer the powerful concept of directed co-evolution for bio-material engineering. Unlike classical directed evolution where only biological elements are optimised, I will iteratively select for high performing bio-material partnerships under stringent criteria. When these outcomes are compared against those from conventional screening, the identification of synergistic, antagonist or purely independent bio-material interactions will be possible. I will then iii) characterise these partnerships to fill large knowledge gaps within the field to understand how synergism can be designed, instead of found. I will employ cyanobacterial hybrids for solar-electricity generation as model systems, targeting final stable photocurrents of near the top theoretical value 2.4 mA/cm2 (>50-fold above typical systems). This work sets the stage for the transformation of other biohybrids and composite functional materials, and the opening up of a new field: the directed co-evolution of hybrid systems.

UKRI Gateway to Research · FY 2024 · 2024-09

The standard model of particle physics is arguably the most successful theoretical paradigm ever developed, accounting for a huge range of fundamental phenomenon with stunning (though at times somewhat frustrating) accuracy. That said, there are several well-rehearsed reasons for believing that it is incomplete: its inability to explain the nature of dark matter, the observed cosmological matter-antimatter asymmetry, or the hierarchy problem between the electroweak and Planck scales, to name a few. Theories that address these problems often predict the existence of new particles at or just above the electroweak scale, which is currently being forensically probed by experiments at the Large Hadron Collider. However, despite an extraordinary range of direct and indirect searches, firm experimental evidence of physics beyond the standard model has proved elusive. In recent years, several measurements performed by the LHCb experiment of rare beauty decays have revealed significant tensions with the predictions of the standard model, which could indicate the presence of new fundamental particles. Observed in transitions of beauty quarks into a strange quark and two charged leptons (b?sl+l-), the 'B anomalies' have generated substantial interest in the theoretical community and motivated a range of theoretical proposals, which generally posit leptoquarks or Z prime bosons with masses in the TeV range. Though apparently compelling evidence for the violation of lepton flavour universality was recently overturned, a number of significant tensions persist in the branching ratios and angular observables of b?sµ+µ- decays. However, since these observables are affected by substantial theoretical uncertainties from hadronic physics, the overall picture is rather unclear at present. I will conduct a new programme of time-dependent measurements of rare beauty decays in order to test the standard model, search for signs of new physics and clarify the B anomalies. These measurements will provide complementary information to time-integrated observables and have not yet been explored at any experiment due to limited data samples. However, in the next few years the upgraded LHCb experiment will collect around five times more rare beauty decays than recorded so far. My track record in rare decays and time-dependent analyses, and my leading role at the LHCb experiment makes me perfectly placed to explore this exciting new frontier. The proposed programme includes time dependent studies of Bs0?µ+µ-, Bs0?fµ+µ-, B0?KSµ+µ- and B0?KSe+e- decays, giving access a range of new observables. I will perform the world's most precise measurement of the Bs0?µ+µ- effective lifetime, which can reveal new physics contributions not apparent in the branching fraction. A similar measurement of the Bs0?fµ+µ- effective lifetime will be used to probe new physics that could be inducing the observed 3.6s tension in the decay's branching ratio as well as a milder tension in the longitudinal polarisation. Core to this project will be achieving a substantive leap in the ability to 'tag' initial flavour of neutral B mesons. Using state-of-the-art recurrent neural networks, I aim to more than double the current tagging power for rare decays, making a range of tagged time-dependent CP-asymmetry measurements possible for the first time. These measurements give access to entirely new observables, many of which are essentially free from hadronic uncertainties, offering clean null tests of the standard model. In addition, I will ensure the research achieves wider impact through a dedicated public engagement programme of talks, articles and podcasts.

UKRI Gateway to Research · FY 2024 · 2024-09

Epithelia are sheets of interconnected cells that cover the surfaces of our body and internal organs. They form physical barriers that protect our body from external insults and control the exchange of materials with the outside. To perform these functions, epithelial cells establish a specialized apical (top) exchange surface that faces the exterior. Defects in epithelial functioning contribute to many diseases, such as cystic kidney diseases, inflammatory bowel disease, and susceptibility to infection. Moreover, loss of epithelial organization is a hallmark of invasive tumours. SurfEx will tackle two urgent interlinked problems that hamper progress in combatting epithelial diseases. 1) the need for highly skilled scientists who can bridge basic research in small model organisms and cell culture with translational research using advanced 3D culture models that mimic the organization and physiology of human epithelia, and 2) the need to improve our understanding of how the apical exchange surface is formed and functions in health and disease. SurfEx brings together academic and private partners from 8 European countries to establish a multidisciplinary, intersectoral training and research programme that will study how epithelial cells form a functional apical exchange surface. SurfEx unites fields ranging from genetics to materials science, microfabrication, and advanced 3D cell culture techniques. This provides an opportunity to train doctoral candidates in a unique combination of experimental approaches and methods, including breakthrough organoid and organ-on-chip technologies. Tight collaboration with non-academic partners will strengthen the technological base of different projects and provides the fellows with insights into the translation potential of the studies and career development opportunities in biomedical industry. Extensive training in transferable skills will round off the training of the fellows into creative, critical, and autonomous professionals.

UKRI Gateway to Research · FY 2024 · 2024-09

The development of efficient, low-cost, and durable doped semiconductors including photovoltaics, light-emitting diodes (LEDs) and transistors will be central to the EU goal of reaching net-zero CO2 emissions by 2050. Taking photovoltaics as an example, the most important aspects for commercialization are the power conversion efficiency (PCE), cost, and durability, which can be combined into the levelized cost of electricity (LCOE) often expressed in euros per kilowatt hour. Multi-junction and bifacial photovoltaics are therefore attractive because they enable power conversion limits associated with monofacial single junctions to be surpassed, lowering the LCOE. MoDCons represents a departure from the broadly adopted strategy of "trial and error", instead driving device engineering strategy with fundamental understanding. Dr Westbrook will achieved this by designing a multi-modal microscopy toolkit capable of quantifying photophysical, chemical, and structural information on the microscale, in next-generation semiconductors. He will deploy this toolkit to understand the structure-function relationships that underpin dopant formation in mixed-metal halide perovskites, with implications for photovoltaics and other optoelectronics. Finally, he will use the multi-modal microscopy toolkit to drive the device engineering of bifacial all-perovskite tandem solar cells to >30% efficiency and >1000h stability. A major academic and industrial effort towards commercialization of next-generation photovoltaics and optoelectronics is currently underway with its epicenter in Europe. Therefore, the postdoctoral fellowship represents a timely opportunity to return Dr Westbrook from the United States to strengthen Europe's base in research and development. Through MoDCons, Dr Westbrook will gain vital skills in device engineering, microscopy and management, securing his future independent academic career.

UKRI Gateway to Research · FY 2024 · 2024-09

I am applying for the DfE Applying Behavioural Insights to Education Fellowship. My proposed research also aligns well with the Ofsted Improving Outcomes Education Research Fellowship. Education is a vital pillar of society, with the power to transform the lives of individuals and communities, and I am excited to use my expertise and passion for education to contribute to a comprehensive understanding of the challenges facing educators and learners. I aim to work towards more effective and equitable education policies and practices through the application of behavioural insights to education. I believe that this fellowship presents a unique opportunity to apply research and evidence to inform strategic education policymaking, shape the country's educational landscape, and ultimately improve outcomes for children and young people. Participating in the policy fellowship program will enable me to gain valuable experience in providing high-quality advice to senior leaders and Ministers in a timely manner. As an experienced researcher, from my previous work with academic and non-academic collaborators, I can offer insights into knowledge exchange within the Government host department. Through the fellowship, I expect to conduct research that will inform policy decisions by examining existing and emerging evidence on education standards and behaviours, conducting evidence-based horizon scanning exercises, and challenging the development of assumptions based on credible evidence. Where possible, I also plan to conduct primary research with stakeholders using innovative research methods to understand the drivers of education behaviours and co-design innovative solutions. Furthermore, as an ONS-SRS accredited researcher with the necessary training and expertise, I also aim to analyze large-scale datasets to identify factors associated with education behaviour and decision-making and provide policy advice to generate new insights of relevance. I hope to gain valuable experience in providing high-quality advice to senior leaders and Ministers in a timely manner. Additionally, I am eager to gain an understanding of government ways of working and policy-making processes, particularly in how research and evidence are utilised and embedded in policymaking. I am also eager to disseminate findings and publish research outputs as academic or policy papers, support capacity development in mixed methods research by designing and organising workshops, and participate in evidence-based future thinking exercises. I firmly believe that this fellowship provides an excellent opportunity to gain proximity to topical policy and delivery decisions at a national scale, inform, influence, and understand sector ways of working to help deliver research more effectively. In conclusion, I believe that the DfE Applying Behavioural Insights to Education Fellowship offers a fantastic platform for me to contribute to education policymaking, expand my professional network, and establish myself as an expert in the utilisation of administrative data to inform evidence-based policy and practice. I would be honoured to have the opportunity to participate in the program and contribute to enhancing the lives of children and learners across the country.

UKRI Gateway to Research · FY 2024 · 2024-09

There is currently an urgent need to achieve renewable based power grids, as a result of the environmental impact of fossil fuel generation as well as due to economic considerations. Wind energy has a significant role to play for the realization of renewable based grids. Nevertheless, achieving a high penetration of wind energy in power grids while retaining an efficient and reliable operation, is a non-trivial problem as a result of the complexity of wind energy systems. In particular, wind power generation is a multi-stage power conversion process, from wind energy to mechanical energy, DC electric power, and then AC electric power. Many models in the literature focus on only parts of this process which is inadequate to achieve a good performance when there is a high penetration of wind generation. Furthermore, potential undesirable oscillatory interactions between the diverse wind energy systems in a power grid further complicates their integration requiring advanced control mechanisms to be implemented. The proposed project aims to address this problem starting with the development of an advanced model for wind energy systems that incorporates its aggregate mechanical and electrical dynamics. This will then be used a basis for designing advanced control strategies for wind energy systems with a grid forming role that will ensure an efficient operation when there is a a large-scale integration of those in a power grid. The work will build upon the existing expertise of the fellow in power electronics and power systems and expertise in control engineering and power system dynamics of the host institution, so as to address this important multidisciplinary problem that is crucial for the realization of renewable based power grids.

UKRI Gateway to Research · FY 2024 · 2024-08

Hematopoietic stem cells (HSCs) ex vivo culture is a fundamental step for HSC-based Gene Therapy (GT), the only curative treatment for more than 10 distinct monogenic diseases worldwide. However, a major clinical challenge for HSC GT arises from the loss of HSC function during ex vivo culture, posing a high risk of delayed or failed blood recovery in patients. Recent work from Laurenti laboratory has demonstrated that more than 50% of functional HSCs are lost within the early adaptation to ex vivo culture with significant transcriptional remodelling in genes linked to metabolism. Metabolic switches are known key regulators of HSC function in vivo. Therefore, the central hypotheses of this proposal are that i) metabolic switches contribute to the early loss of human HSCs regenerative capacity during ex vivo culture, ii) targeting metabolic switches pharmacologically can improve HSC function ex vivo. This proposal will first generate a kinetically resolved map of metabolomic switches occurring during human HSC ex vivo adaptation. For this, I will integrate metabolomic analysis on highly purified human HSCs cultured in preclinical GT conditions with scRNA-seq data. My preliminary work, using computational methods on time-course scRNA-seq and functional assays with small molecule inhibitors, has identified purinergic metabolism fluxes as dynamically changed and pharmacologically targetable during HSC ex vivo adaptation. Therefore, in my second aim, I will screen the effects of pharmacological inhibition of key purinergic enzymes to determine how the purinergic metabolic switch: i) regulates HSC function ex vivo and ii) affects HSC regeneration using a preclinical model of HSC GT. This project will generate new insights into the interplay between stem cell metabolism, stress and regeneration. In addition, it will identify new preclinical strategies to improve HSC function ex vivo, with direct relevance to HSC GT and other clinical applications requiring HSC culture.

UKRI Gateway to Research · FY 2024 · 2024-08

Adults today make up a very large percentage of language learners. In a globalised world, record numbers of adults are motivated to learn a new language; and far too often, pathology from stroke, dementia or even normal ageing can require adults to re-learn specific language skills. Unfortunately, language learning outcomes are dismal in adults. Yet evidence suggests that adults are excellent learners, and even display a substantial amount of brain plasticity in the language networks, pointing to a critical gap in our understanding of why language in particular presents such difficulty. The goal of this proposal is to develop a mechanistic understanding of language learning in adults by unifying theories from memory, psychology and language research, and to test our predictions for facilitated language learning in ageing and pathology. I will perform a systematic study of the memory processes underlying language learning in adults by using a language-learning paradigm grounded in psycholinguistic theories, and collect behavioural and fMRI data to (i) test a neuroscientific model of memory and its predictions for better language learning in healthy young adults and the underlying neural mechanisms, (ii) test its predictions of specific patterns of change and optimal learning conditions for healthy older adults, and (iii) test its predictions for better retention in patients with different types of memory deficits. This comprehensive approach will also answer an open question at the heart of memory research about the pivotal role of the hippocampus in memory, i.e. whether it can in fact be by-passed in learning under specific conditions ("fast-mapping"). Thus this project will bridge an important theoretical gap between two fields, answer critical questions in the fields of both language and memory research, and provide proof-of-concept for translational applications in improving learning in healthy older adults and patients with different types of memory deficits.

UKRI Gateway to Research · FY 2024 · 2024-08

Our project will produce the first ever 'history from below' account of women working in the Portuguese and Spanish industries in the 1970s, by focussing on below-the-line roles, such as editing, costume design and production management, and paying attention to the ways these roles criss-crossed between film and television. We focus on the 1970s, when the ending of fascist dictatorship in both political contexts shaped Portugal and Spain in ways that are productively comparable but far from identical. While Portugal's dictatorship was overthrown by a left-wing coup triggered by colonial war in Africa, Spain's transition was negotiated after Franco died in his bed. Subsequent legislation changes in both countries permitted women to work outside the home, and this was the point at which they joined crucial below-the-line film and television professions in significant numbers. Indeed, some roles, such as editing and casting, were performed almost exclusively by women. Below-the-line jobs are usually seen as replaceable, and their contribution to a finished film or TV programme is of little note. While scholars have already paid attention to the very few women in above-the-line roles in the period, we will examine the women who have provided these alternative forms of low-visibility leadership in greater numbers. They have so far escaped the eye of scholars, because above-the-line roles, particularly in film, confer prestige, attract international recognition and promote agency. Our project will thus also add the critical transnational dimensions of Spanish and Portuguese history to current worldwide, predominantly Anglophone, debates on women in the film and television industries today. In the context of film, our first area of impact is, therefore, increasing intercultural knowledge of women in world cinema, through subtitling, streaming and screenings. As part of the Exeter 'Subtitling World Cinema' project (SWC), we select 6 key feminist films of the 1970s from Portugal and Spain that are currently inaccessible to Anglophone audiences. We will secure copyright to subtitle them into English for the first time, make them freely streamable, and screen them to wide publics. This will democratize access to world culture, increase inter-cultural knowledge and allow Portuguese and Spanish film to be more fully part of current #metoo debates about film and feminism today. Our second area of impact, working on both film and television, will engage future professionals by working with film festivals in each country and with Portugal's Plano Nacional de Cinema, and Spain's Cine y Educación (Academia), both Department of Education projects for schools. Through screenings, roundtables and workshops, we will bring the key decade of the 1970s to the attention of the current generation and address the problem that, while there is c. 65% female participation in media studies University departments in Portugal and Spain, this yields only 20% female participation in industries that still resist their incorporation. By championing leading women in still largely invisible below-the-line roles, including in television, we engage with wider debates, and specific feminist activism campaigns including Spain's Association of Women Filmmakers, CIMA's #masmujeres and the Berlin-based Proquote-Film organization, promoting female capacity in all areas of the industry. Using archival research, oral history, film and television analysis, memory studies and comparative studies, this project will yield two co-authored research monographs, two edited volumes of interviews, one project conference (with published proceedings) and one conference linked to the commemorations of the Portuguese Revolution 1974 (with a journal special issue). Moreover, it will disseminate 6 subtitled films and a series of awareness raising events at 9 UK, Portugal and Spain festivals including our partner festival VIVA, curated by HOME (Manchester).

UKRI Gateway to Research · FY 2024 · 2024-08

Expressivity - the signalling of the speaker's perspective on the utterance - has long been considered a secondary function of language, but recent work shows that it is far more structured than previously thought. A prominent proposal argues that expressive meaning is conveyed by 'marked morphology' (MM), i.e. functional morphemes which appear in a deviant (marked) structural position. However, the scarcity of systematic investigations is a serious obstacle for our understanding of the exact encoding of expressivity in human language. The goal of the FEMOR-project is two-fold, namely i) conduct an in-depth comparative study on expressivity strategies, and b) couch the theoretical analysis of this new empirical knowledge in the recently taken highly promising theoretical direction towards the formalization of expressive meaning in morphosyntax. Afrikaans and Dutch form an ideal empirical domain for this research as a) they share two clear manifestations of MM with expressive meaning, and b) only Afrikaans also displays expressivity in a common (language-internally unmarked) morphological process, i.e reduplication (RE). By i) systematically collecting data on the morphosyntax of MM and RE, and ii) analysing the data with exploratory statistical techniques prior to developing a detailed formal analysis, the FEMOR-project will make significant progress in the formalization of expressive meaning in morphosyntax, and deepen our understanding of the pragmaticalization and grammaticalization of expressive elements.