University of Cambridge

UKRI Gateway to Research · FY 2025 · 2025-06

This project seeks to develop a high-sensitivity, low-cost sensor platform with a wide range of uses. To bring focus to the work, we will target for point-of-care bio-sensing, and specifically will use as an exemplar the detection of the circulating tumor DNA (ctDNA) due to the well matched requirements for ultra-high sensitivity, rapid results and portable system which cannot be currently addressed by other means. Optical micro-ring resonators hold great potential for sensing. Their ability to produce very high quality resonance with light circulating around a loop many times before being lost enables very high sensitivity between the circulating light and the external influences. However, as well as being highly sensitive this process is hard to control. To achieve the best sensitivity, the amount of light lost per circulation has to be extremely low, and can only be achieved with complex manufacturing processes. At the same time, the readout system typically relies on expensive and bulky tuneable wavelength lasers. We seek to overcome both problems using a combination of low-cost polymer (plastic) resonators and a readout scheme method where a microwave frequency sweep modulated on an optical carrier is used rather than an optical wavelength sweep. Typically the achieved tolerances of polymer waveguides are less good than other material systems (e.g. silicon) resulting in lower Q factors, we will overcome this by refining the nano imprint fabrication process and also leveraging the readout scheme which allows the signals used for the readout to be tailored to the specific imperfections of an individual micro-ring resonator. By overcoming the difficulties associated with the use of polymer micro-rings, we expect to realise many benefits. Polymers are low cost, and particularly well suited to functionalisation with biomolecules which do not stick well to other surfaces, so we expect to find a wide range of applications in healthcare diagnostics as well as wider sensing applications. Our ultimate aim within this project is to demonstrate the ability to detect low levels of ctDNA of actionable mutations in human subjects with non-small cell lung cancer. The use of genomic and molecular information is now standard in the treatment of lung cancer though routine testing still requires several weeks for the results to return to the ordering clinician. A rapid point of care detection and classification of ctDNA will accelerate this process and likely lead to improved patient outcomes

UKRI Gateway to Research · FY 2025 · 2025-06

The degradation of natural habitats and farmland undermines efforts to keep global warming below 2°C, and to meeting the United Nations Sustainable Development Goals. The COP26 'Glasgow Leaders' Declaration on Forests and Land use' commits over 100 nations to work together to halt and reverse forest loss and land degradation by 2030. This reaffirms international commitments under the Bonn Challenge to 'restore' 350 million hectares by 2030, a goal set in response to a scientific report indicating that 300-400 million hectares of forest needed to be restored to avoid dangerous climate change. While restoration promises to slow climate change, reverse biodiversity loss, and recover soils, 21st century restoration science lacks a joined-up understanding of the effectiveness of different tree planting options and how their roll-out may generate unintended consequences, especially by the displacement of food or wood production that leads to habitat loss and greenhouse gas emissions elsewhere. The risks of poorly planned and executed large-scale tree planting include restoration failure, deforestation via displacing farming to other areas, and fragmentation of open habitats. There is thus a pressing need to move beyond traditional individual project-level assessments of restoration that may fail to detect these complex and larger-scale impacts. Here we will conduct novel analysis that explicitly account for feedbacks that generate unintended consequences for biodiversity and ecosystem services at large spatial scales. We will implement a region-wide analysis to quantify the effectiveness of different restoration interventions and resolve the degree to which they displace food or wood production. In this way, this project will address the major uncertainty in restoration. This continent-scale integrated programme of research focuses on wooded savanna ecosystems in 14 countries in sub-Saharan Africa, where ~90 million hectares of wooded savanna restoration are planned. It will use the known locations of over 1000 restoration projects implementing the most commonly applied restoration techniques (natural regeneration, tree plantations, and on-farm approaches). Using these data, we will answer the following core questions: (1) How have restoration projects impacted habitat and carbon storage in the project areas (effectiveness)? (2) How much displacement (leakage) of deforestation, wood overharvesting, and tree growth to non-project land do restoration programmes cause? And (3) what are the environmental and socio-economic drivers of restoration effectiveness and leakage? In answering these three questions, this project will deliver a step change in our understanding of the likely consequences of continental-scale restoration, increasing the prospect of achieving its ecological and societal potential and meeting global climate and development goals.

UKRI Gateway to Research · FY 2025 · 2025-06

Debris disks are the disks of asteroids, comets, dust and gas that surround nearby stars. Such debris is found in the cold outer (>30au) region of planetary systems to ~20% of stars. A similar fraction of stars host warm dust in their inner (<30au) region, which are known as exozodi by analogy with the solar system’s zodiacal cloud. Exozodi dust resides in the middle of the region where the star’s planets should reside and its structure is expected to be strongly influenced by the planetary system architecture, which is generally unknown. It has recently become possible to spatially resolve and characterise exozodi with LBTI, JWST and ALMA. This project aims to develop modelling techniques to determine the structure of exozodi expected for a given outer debris belt and planetary system. Current exozodi modelling techniques are limited by the need to combine gravitational and radiation forces with collisions and gas drag. This proposal will develop an approach that the PL has pioneered, in which N-body simulations trace the evolution of comets with debris released from them being passed to a kinetic code to follow its evolution due to collisions and radiation forces. The areas of development include: (1) exploration of planetary system architectures, development of a Monte Carlo scattering model to circumvent N-body simulations; (2) incorporation of planetary perturbations (ejection and resonant trapping) into the kinetic code via empirical functions; (3) following gas released using a hydrodynamic code and incorporating its influence on dust evolution through the kinetic code; (4) following accretion of debris onto planets to assess mass accretion and its effect on planetary atmospheres. The models developed will be applied to cutting-edge observations of exozodi that the project has access to (from LBTI, JWST and ALMA) to set unique constraints on the planetary system architectures of nearby stars. This will result in improved understanding of exozodi formation mechanisms (e.g., distinguishing between cometary and P-R drag replenishment mechanisms) and this will be used to make better predictions for systems where imaging is not yet possible. This is vitally important for our search for habitable exo-Earths, since exozodi provide noise that can hinder exo-Earth imaging while also being a signature of bombardment that can affect planetary habitability.

UKRI Gateway to Research · FY 2025 · 2025-06

It is now widely accepted that the "golden age" of antibiotics has passed, and that antimicrobial resistance (also known as "AMR") is on the rise. One extremely useful tool in the fight to understand AMR has been whole genome sequencing, in which the entire genetic "blueprint" of an organism can be elucidated. Using whole genome sequencing, researchers have found that mutations in certain genes are strongly associated with AMR. FusA1 is one such gene, and mutations in fusA1 are now recognized as being responsible for high level resistance to an important class of antibiotics called aminoglycosides. More worryingly, these mutations are particularly prevalent in an organism called Pseudomonas aeruginosa (hereafter, PA), which is ubiquitous in the built environment and is a major cause of potentially life threatening infections, especially in people who are less well able to fight such infections. The problem is that we currently have little idea about why mutations in fusA1 lead to AMR, and without this understanding, there is little we can do about this. FusA1 encodes a protein involved in making other proteins; a process called "translation". Here, mini-factories known as ribosomes "translate" the information coded in a molecule called messenger RNA (which itself, is copied from the DNA blueprint) to make all the proteins needed in the cell. The function of FusA1 is to help the ribosomes to "drop off" the RNA once they have made each new protein, or if they encounter a "stall signal". Ribosomal pausing at most stall sites is usually easily overcome if the FusA1 is functioning normally. However, based on our preliminary experiments, we suspect that the ability of mutant forms of FusA1 to facilitate this "ribosome recycling" reaction may be altered, thereby changing the dynamics of translation. For example, if dissociation of ribosomes from key "stall sites" or stop signals is even slightly impaired, ribosomes will start to queue-up at such sites, affecting the translation of the protein encoded on the messenger RNA. If that protein was itself associated (either directly or indirectly) with aminoglycoside resistance, this would provide a tangible link between the mutation in fusA1 and the AMR phenotype - a hypothesis that we are very keen on exploring using state-of-the-art approaches called RNA-seq, Ribo-seq and ChIP-seq. We also suspect that mutations in fusA1 might alter its ability to bind to other molecules in the cell, including other proteins or non-messenger RNA. Cutting-edge technological developments mean that we can now investigate these hypotheses directly using specialized "proteomic" approaches called TurboID and "OOPS", respectively. To increase the probability of success, these approaches will be carried out in collaboration with world leaders in their respective disciplines. By the end of this project, we will have a clear idea about how mutations in fusA1 lead to aminoglycoside resistance. This "mechanistic" understanding will be critical if we want to find better ways of combatting AMR, or of better predicting the AMR phenotype of a strain based on its whole genome sequence (an approach that, with ever-cheaper and faster sequencing, is likely to become widespread in the clinic in the near future). Excitingly, our preliminary data indicate that in principle, it is possible to reverse the AMR associated with fusA1 mutations, offering a line-of-sight - albeit, beyond the scope of the current proposal - towards resensitizing resistant PA to aminoglycoside antibiotics.

UKRI Gateway to Research · FY 2025 · 2025-06

Context Transportation accounts for 1/5th of global CO2 emissions from energy and about 20% of that could be reduced through lightweighting of metallic components. A promising strategy to achieve that is to use net-shape manufacturing processes—such as additive manufacturing (AM)—to re-design parts with optimised geometry and to employ low density materials, such as aluminium (Al) alloys. The main problem with this strategy, however, is that Al parts made by AM exhibit sub-optimal properties, which hinder their certification and use in safety-critical applications, such as in aviation. The connection enabled by this project This project will promote collaborative work between the University of Cambridge (UoC) and the National Centre for Additive Manufacturing (NCAM) as part of the Manufacturing Technology Centre (MTC) to devise scalable AM processes for lightweight Al structures that are of interest to their industrial members, such as Airbus. The project will capitalize on the microstructure control strategies developed by the UoC research group, which will be applied to an alloy system selected by the MTC and which will be scaled up for technology validation (TRL4-6). As such, this project aims to bridge the gap between fundamental research and industrial application and—by working with Airbus—to promote the adoption of AM for sustainable aviation. The challenge addressed Laser-based AM processes typically yield builds with heterogeneous microstructure and anisotropic properties. This is due to the variable and directional thermal flux experienced by the material during AM. As a result, AM parts must undergo involved and costly heat treatments aimed at homogenising their microstructure to bring their properties within specifications. This additional hurdle hampers the adoption of AM by the industry, offsetting the potential of this technology for lightweighting and thus for reducing carbon emissions in transportation. Aims and objectives This project will directly address the above challenge. Focusing on a special Al alloy—called Aheadd® CP1 (developed by Constellium)—which has been designed specifically for laser-based AM, the research team will demonstrate the ability to make samples and miniaturized parts with controlled microstructure and mechanical properties (including yield stress, impact energy, and fracture toughness), which are within the specifications set by Airbus. The work will consist of two consecutive steps: i) inducing microstructures that can be homogenised via traditional heat treatments, thus streamlining the production of Al parts by AM, and ii) producing parts that exhibit the desired, homogeneous microstructure in their as-built condition, and thus require no additional heat treatment whatsoever. Potential applications and benefits The direct beneficiary of the work is Airbus. The company has great interest in using AM technology to optimise the geometry of Al parts used in aircraft. However, the involved and costly post-processing required to certify parts has offset the adoption of AM significantly so far. One potential application of this project outcomes is in the manufacturing of topology-optimised, high-strength landing gears in civil aircraft. The project will also benefit the team at UoC, who will be able to translate their materials processing strategies and microstructure designs from the lab to real-world applications.

UKRI Gateway to Research · FY 2025 · 2025-06

Amyotrophic lateral sclerosis (ALS) is a severe disease which gets worse with time and causes the breakdown of specific type of brain cells, motor neurons in both brain and spinal cord. This leads to a gradual loss of muscle function and, eventually, death. Currently, the only FDA-approved drugs for ALS, Riluzole and Edaravone, provide only modest benefits, extending life by a few months at best. There are no effective therapies that directly address the underlying causes of the disease. Micro-RNAs (miRNAs) have been found increasingly implicated in ALS due to the dysregulation of these molecules observed in ALS spinal cord and motor neurons. For example, miR-155 and miR-125b are found at higher levels in ALS patients, where they contribute to the death of motor neurons and cause inflammation. Blocking these specific miRNAs in laboratory models of ALS has shown promise, protecting motor neurons and extending survival in mice. This suggests that targeting miRNAs could be a new way to treat ALS. Developing miRNA-based therapies faces challenges, especially with delivering synthetic miRNAs or inhibitors (called antagomirs) effectively inside the central nervous system. To overcome these obstacles, researchers are focusing on small molecules that can regulate miRNA activity by interacting with their unique structures. High-throughput screening methods are being used to identify such small molecules quickly. The proposed research focuses on finding inhibitors for miR-155 and miR-125b using a step-by-step process. 1. Primary Screening with Small Molecule Microarray (SMM): One hundred thousand of small molecules will be screened to identify those that interact with miR-155 and miR-125b. MiRNAs will be labelled with fluorescent tags to establish how small molecules affect their fluorescence, indicating a potential interaction. This approach allows rapid testing of many molecules and helps identify promising candidates for further study. 2. Secondary Screening for Validation whereby two methods will confirm the findings from the primary screening: Affinity Selection Mass Spectrometry (AS-MS): This method identifies small molecules that bind to miRNAs by separating and analyzing the resulting complexes. Differential Scanning Fluorimetry (DSF): This technique measures changes in the stability of miRNA structures when small molecules bind to them. Using both methods ensures accurate results and validates the effectiveness of the identified molecules. 3. Testing for Blood-Brain Barrier (BBB) Crossing: ALS treatments must reach the brain and spinal cord, so the small molecules’ ability to cross the BBB will be evaluated using imaging tools like PET scans. These scans allow researchers to track how the molecules behave in the body and determine their potential for treating ALS. This research is unique because it explores not only individual inhibitors for miR-155 and miR-125b but also their combined effects. Targeting both miRNAs simultaneously might reduce inflammation more effectively, providing new insights into their role in ALS. If successful, this study could identify small molecules capable of regulating miRNAs and reducing neuroinflammation in ALS. These molecules could form the basis for new, innovative treatments that address the disease's root causes. Moreover, the screening techniques developed could be applied to study other miRNAs and neurodegenerative diseases, broadening the impact of the work. In summary, this research aims to tackle ALS by focusing on miR-155 and miR-125b as therapeutic targets. By identifying and testing small molecules that inhibit these miRNAs, the project hopes to create new treatments for ALS and advance understanding of miRNA biology.

UKRI Gateway to Research · FY 2025 · 2025-05

MASAUTO is a research and training program for 10 early stage researchers (ESRs), focusing on developing a new generation of materials that will overcome the current bottlenecks in the capability and capacity of autonomous sensors. The design of materials for remote sensing applications, such as real-time information on climate changes or for intelligent transportation systems, still represents an enormous challenge. The ongoing exponential growth of the internet of things (IoT) ecosystem - which could reach a trillion devices in the near future - poses a serious challenge in terms of powering and interconnecting the underlying devices. The full potential of the IoT will only be achievable if devices i) have a reliable and sustainable autonomous power supply, and ii) are capable of processing information with reduced power requirements. A promising approach to address the first challenge is the use of an energy harvester-supercapacitor combination, while for the second challenge a promising strategy is the use of non-volatile random access memories. It's, therefore, crucial to develop materials for energy harvesting and storage, as well as low loss electronics. Through MASAUTO, we will create a highly trained cohort of scientists and technologists, enabling rapid and broad commercialization and implementation of technology in public and private research centers and in industrial institutions. The ESRs will acquire a solid multidisciplinary scientific training, from basic science to industrial applications, which will enable them to generate new scientific knowledge of the highest impact. MASAUTO will also deliver practical training on transferable skills in order to increase employability prospects and to provide the researchers with access to highly skilled employment opportunities in the private and public sectors. The overarching aim of the network is to position Europe as a leader in autonomous sensors for smart healthcare, automotives, industry and agriculture.

UKRI Gateway to Research · FY 2025 · 2025-05

The Academy for the Mathematical Sciences (AcadMathSci), catalysed by the Isaac Newton Institute for Mathematical Sciences (INI), represents a transformative initiative for the UK’s mathematical sciences community. This proposal seeks funding from EPSRC to support the Academy’s central activity of Mathematical Sciences Communication, enabling us to promote excellence in boundary-breaking research and to harness the power of the discipline for the benefit of society, the economy, and the field itself. With the continued support of INI during this transitional phase, the Academy will build on its foundational structures, national mandate, and extensive networks to deliver impactful and far-reaching outcomes. Context The creation of the Academy for Mathematical Sciences is a once-in-a-generation opportunity to unify voices across academia, education, business, industry, and government. By fostering multi-way communication and addressing systemic barriers, the Academy aims to amplify the vitality and impact of the mathematical sciences in addressing national and global challenges. Our efforts span all four nations, ensuring that the benefits of mathematical sciences are felt across the UK. The Challenge Despite its extraordinary contribution of £495 billion annually to the UK economy and its critical role in areas such as AI, climate science, and healthcare, the value of the mathematical sciences is not widely understood or appreciated. Public perceptions of mathematics remain negative, with many viewing it as inaccessible or intimidating. This has led to underutilisation of the discipline in addressing pressing societal challenges, as well as a lack of engagement with mathematical sciences by potential students, policymakers, and the general public. Aims and Objectives This project seeks to: Foster excellence in research by enabling two-way dialogue between mathematical scientists and stakeholders across government, industry, and education. Shift public perceptions of mathematics through broad public engagement campaigns and targeted interventions. Address societal challenges by highlighting the critical underpinning role of mathematical sciences in fields such as renewable energy, public health, and quantum computing. Build communication capacity within the mathematical sciences community to amplify its collective voice and influence. Inspire future generations by showcasing career opportunities unlocked by mathematics and data skills. Proposed Activities The Academy will: Enhance multi-way communication by bringing together leaders from government, business, and academia to identify challenges that can benefit from mathematical expertise. Develop tools and training to help policymakers, CEOs, and other stakeholders better leverage mathematical insights for decision-making. Launch public campaigns, such as the successful “Maths Can Take You Anywhere,” to celebrate relatable success stories and inspire the next generation. Create accessible resources to showcase the impact of mathematics, including primers for policymakers and case studies from REF Impact databases. Potential Applications and Benefits This project will address key societal challenges, from climate resilience to AI validation, by embedding mathematical sciences more deeply into public and private decision-making processes. It will: Foster a culture of collaboration and effective communication within the mathematical sciences community. Equip policymakers, educators, and business leaders with the tools to utilise mathematical insights. Shift societal narratives around mathematics, making it more accessible and inspiring broader engagement. Create a pipeline of skilled professionals equipped to address challenges in a modern economy. By leveraging its unrivalled convening power and extensive networks, through this grant the Academy for the Mathematical Sciences  will deliver a step change in the visibility, vitality, and impact of the mathematical sciences in the UK and beyond.

UKRI Gateway to Research · FY 2025 · 2025-05

The last decade has been hallmarked by an explosive rise in digital communication. Technologies such as social media present a profound challenge, especially for young people. In parallel, we are experiencing a growing mental health crisis in this population. This project undertakes a transformative mission to unravel, test and enhance policies that counter the detrimental impact of social media on young people, to safeguard and amplify their well-being in our increasingly digital world. Employing a cutting-edge comparative approach, the research will encompass systematic literature synthesis, qualitative exploration, field experiments, and computational analysis. By differentiating between preteens (ages 10 to 12), adolescents (13-17), and young adults (18-25), the project will uniquely pinpoint effective policies tailored to each population. WP1: We will synthesize current policy interventions through an exhaustive and structured literature search. WP2: We will use qualitative focus group interviews with each age group, to investigate age-group perspectives and co-create potential policy interventions. WP3: Focusing on young adults, in an online field experiment we will test the effectiveness of such policy interventions on a mock website via the manipulation of designs, usage patterns, or content. WP4: Computational simulations will enable us to build theoretically informed models extrapolating our findings from WP3 to preteens and adolescents. WP5: We will integrate the project findings to assess the feasibility and usability of established and new policy interventions across Europe, providing evidence-based recommendations. Our interdisciplinary approach draws upon the expertise of leading scholars from Communication, Psychology, Sociology, and Media Studies to systematically locate, test and evaluate policy approaches that tackle the impending mental health crisis among young people, thereby contributing to the well-being of generations to come.

UKRI Gateway to Research · FY 2025 · 2025-05

Among the designs of advanced nuclear reactors being investigated worldwide, one concept holds a particular promise to make significant impact and address the global needs for clean energy sources in the near future - the molten slat-cooled high-temperature reactor, also known as Fluoride slat-cooled High-temperature Reactor (FHR). Unlike traditional Molten Salt Reactors (MSRs), the FHR uses solid fuel, which simplifies the concept greatly and can speed up its development and deployment. The advantages of FHR reactors over the current LWR designs and their economic benefits were highlighted in the AGRESR project concluded in 2021. Even though FHR concept presents many advantages in simplicity (when compared to molten slat-fuelled reactors), safety and economics, a significant amount of development is still needed. The concepts pursued elsewhere require substantial investment in the development of new fuel, core design and materials. Therefore, taking advantage of existing technologies and experience can substantially reduce the time needed to develop and deploy a salt-cooled reactor. Previous work explored the possibility of adopting features from the British Advanced Gas-Cooled Reactors (AGRs) to speed up the development and commercialisation of FHRs. AGR development in the UK suffered from notable initial challenges, but the resulting product was an impressive fleet of nuclear reactors, which remains unmatched in its availability and efficiency. Thus, borrowing knowledge and expertise gained in years of AGR operation and their implementation in FHR is an attractive proposition. Recent analyses showed that the best performance of an AGR-like FHR system is achieved in configurations with only a small amount of graphite in the core, and, possibly, no graphite at all. This finding implies substantial deviation from typical AGR fuel geometry and core layout affecting the behaviour of the system. Therefore, several questions remain to be addressed, which will form the scope of this proposed project. It was shown that power density of the core can be substantially increased, allowing to produce more power from the same for or significantly reduce the core. Small modular AGR-like FHR core design has never been attempted. The previous fuel cycle analysis used simplified assembly models. Therefore, the findings would need to be confirmed on a more realistic full core level. It would be required to identify and analyse the most relevant limiting accident scenarios for the new core in order to make a compelling safety case. Unlike AGRs, the new system operates at nearly atmospheric pressure, suggesting that refuelling procedures can be simplified. Currently operating AGRs do not refuel at full power. This is partly due to concerns over vibrations and coolant flow redistribution among the neighbouring channels introduced by the fuel assembly extraction. Demonstrating possibility of refuelling at full power would be a major advantage of the new system. The changes in the core configuration mean that many questions related to salt fluid dynamics need to be addressed through experimental investigation. These, for example, should include evaluation of pressure losses imposed by support grids and those due to deposits and corrosion of surfaces which can change its roughness. These effects need to be quantified for different flow regimes. Finally, alternative fuel and coolant options can be explored. For example, metallic and dispersed particles fuels as well as coolants other than traditional FLiBe salt can offer many performance advantages.

UKRI Gateway to Research · FY 2025 · 2025-05

Wearable devices have become pervasive and generating a lot of data which is indicative of our behaviour and physiology. This offers an unprecedented and detailed window onto human wellbeing, fitness as well as the potential for scalable public health and clinical monitoring tools. Recently, hearables have started to be used for a variety of activities ranging from the traditional music listening to more advanced fitness activities (such as running). During and following the pandemic, individuals have been commonly using these for all their virtual meetings too. Emerging companies are starting to market the devices also as comfortable sleeping aids. Hearable devices, placed on a person's head have also higher potential for detection of stable physiological signals with respect to watches, as arm movements are very pronounced and often affect sensors on watches, especially during full body movement, and hearables offer two channels (left and right). Yet, while hearable devices are indeed on the market in some form, their functions are generally still fairly restricted to means of transmission of audio and speech. Their ability to detect physiology, especially under motion and considering head and face macro and micro movements is also unproven. Additionally, they are not treated as standalone devices but they are usually dependent on smartphones for further computation and communication. Finally, the precious data generated usually, like for many other wearables, flows to commercial servers for analysis, potentially exposing users to privacy invasion. In general, there have been questions on the precision of data from wearable concerning our wellbeing and health: the sensors on these devices are often imprecise and various factors contribute to making the inference over this data hard (movement, variety of use, heterogeneity of human characteristics, etc). In this proposal I plan to advance the research on hearable sensing in fundamental ways to enable these devices to become truly reliable, trustworthy and privacy aware means of detection of our activity, fitness and health. The potential of such technology is immense: hearables are small and some versions are already very affordable, certainly more affordable than clinical diagnostics or fitness monitoring equipment. They are also more portable and people tend to wear them throughout their day (and sometimes nights, in the case of sleep hearables): this means that they have the potential of sensing the users continuously generating very precious longitudinal data which would impact the way in which we study personalized fitness as well as clinical disease progression, onset and recovery. The scalability enabled by such technology means that large populations can be reached and yet the temporal granularity of the data (i.e., the almost continuous monitoring of individuals) is not compromised, enabling public health and epidemiological studies to scale. Some of the findings of this work will impact the research in wearables and wearable data analysis in general, opening the door to a wide range of applications. More precisely the programme will innovate on the type of sensors which can be used to sense activity and health, the machine learning methods applied to this data and the systems aspects related to this which include the ability to run the models on device or explore the trade offs of local and remote computation. HearFit will also conduct extensive user studies in the context of fitness and health through collaborations with sport scientists and clinicians.

UKRI Gateway to Research · FY 2025 · 2025-05

Context: The kidneys play a vital role in cleaning the blood and controlling the body's water balance. Unfortunately, their function may be affected by a number of common diseases including high blood pressure, diabetes and autoimmune inflammation. Ultimately, these kidneys diseases cause scarring, leading to poor kidney function or 'chronic kidney disease' (CKD for short), a condition that becomes more common with increasing age, and affects hundreds of millions of people worldwide. In some patients with CKD, progressive scarring can lead to kidney failure, which is treated with blood cleaning therapy (dialysis) or a kidney transplant. However, because of organ shortage, and long waiting lists for a transplant, there is an increasing use of kidneys from older donors or those with medical problems that cause kidney damage. Therefore, some of these kidney transplants can also be affected by CKD and develop progressive scarring post-transplant, that ultimately leads to graft failure. The Challenge: There are currently no treatments that specifically prevent the development of irreversible kidney scarring in either native or transplanted kidneys. Project aims and outline: We will recruit kidney transplant patients with CKD that have scarring on a biopsy sample, but no rejection. We will ask them if they would be willing to try a new, immune-modifying treatment called avacopan. Avacopan blocks an immune sensing molecule (C5AR1) that we have found on the most abundant immune cell type found in kidneys - macrophages. Macrophages can contribute to kidney scarring. Patients entered into the study will be randomly assigned to receive avacopan, or a placebo tablet for 12 months. After the 12 months all patients (whether they were on placebo or avacopan at the beginning) will be given avacopan for another 6 months, so that all patients recruited can potentially benefit from the treatment. To understand how avacopan is working, and whether it can be used in CKD, we will take kidney tissue, as well as blood and urine samples. We will use standard measures of kidney function and kidney scar tissue, as well as new types of technologies to analyse immune and tissue cells, to produce a clearer picture of the effects of avacopan treatment. Some of these new technologies use information about how the genetic code of cells is translated into action, by measuring genetic messenger molecules called 'RNA'. The Clatworthy lab are international experts in studying RNA, down to the level of individual immune or tissue cells, and they can also match up this information with the location of these cells in the kidney, and to changes in blood and urine, providing a comprehensive view of the effects of the drug. Applications/benefits: This information will tell us whether avacopan (or other drugs affecting this immune pathway) could be used to prevent kidney failure in patients with CKD regardless of the underlying cause, helping millions of patients worldwide.

UKRI Gateway to Research · FY 2025 · 2025-05

Heterogeneity is a common feature of large, high-dimensional datasets. A simple form of heterogeneity in data ordered by time is a change in the data generating mechanism at certain unknown time instants. For example, monthly economic data may be affected by changes in government policy or in import/export regulations of other countries. A key question is: how can we fit accurate statistical models for high-dimensional data in the presence of such change points?  Change points are the time instants where the underlying generative mechanism changes. The challenge in fitting regression models is especially acute with modern datasets, where even the number of change points is often unknown. The predictions of a model may be highly misleading if the change points are not estimated accurately. This project addresses the challenge of detecting change points in high-dimensional regression models, where the data dimension is large and comparable to the sample size. We will develop a novel technique for change point regression based on weighted empirical risk minimization (weighted ERM). Our approach allows prior information on the  changepoints to be encoded via Bayesian weights. For example, the weights could encode a minimum separation between the change points. The weighted ERM approach allows us to adapt standard convex penalized estimators (such as LASSO and sparse logistic regression)  for change point detection. The  weighted ERM estimator is as easy to implement as the underlying convex estimator, with complexity of the same order. We will demonstrate the performance of the technique using datasets drawn from fields ranging from the medical sciences to econometrics. Moreover, we will establish rigorous guarantees on the performance of weighted ERM on high-dimensional data, including a computable posterior distribution on the change points. The weighted ERM technique developed in this project is practical, and can be applied for change point detection in a broad class of  generalized linear models, including the widely used logistic, probit, and Poisson models. Generalized linear models are a workhorse of statistics, and are widely used for regression and classification in  biology, medicine, economics, and many other fields.  The project will provide a powerful, easy-to-use, set of tools for analyzing the heterogenous, high-dimensional datasets often encountered in these areas.  Drawing on ideas and techniques from high-dimensional statistics, information theory, and signal processing, the project will establish novel theoretical and algorithmic connections between these areas. We expect that it will open the way to a much broader investigation of heterogeneity in high-dimensional data.  

UKRI Gateway to Research · FY 2025 · 2025-04

The evolution of plants has given rise to extraordinary diversity, that has colonized virtually every planetary environment, including the most extreme. Extremophile plants display remarkable evolutionary adaptations to survive in severe and inhospitable conditions. Exploring these adaptations is not only compelling but of fundamental significance. Here, we have recently made an intriguing discovery: a unique assemblage of high-altitude Himalayan plant species that exhibit floral heating to 20C above ambient. These include two types of floral-heating mechanisms: "glasshouse plants" which amplify heat by capturing solar radiation, and newly discovered "thermogenic plants" which generate their own heat. The coexistence of thermogenic and glasshouse species suggests floral heating is an underexplored, yet critical, adaptation for survival in these Himalayan ecosystems. In this research proposal, we set out to achieve several related objectives. First, utilizing thermal imaging, we will elucidate the complex temperature dynamics exhibited by these floral-heating species and investigate how temperature modulations influence pollinator behaviours. This will uncover mutualistic co-evolutionary relationships between floral-heating plant species and their pollinating insects. Second, we will resolve the evolutionary history of these floral-heating species and their divergence from non-heating ancestors. This will provide insights into the evolutionary processes that led to the emergence of floral heating as an adaptive strategy. Third, we will evaluate the ecological role these species play in maintaining insect biodiversity and pollination services within the Himalayan ecosystems. This will help us understand the broader implications of these adaptations for ecosystem health and resilience. Our multi-scale investigation promises fascinating insights, significantly contributing to our understanding of both ecology and evolution, from species to ecosystem.

UKRI Gateway to Research · FY 2025 · 2025-04

Ribosome assembly is a highly conserved process that is essential for cellular protein synthesis. Better understanding of this fundamental cellular process is important as the “addiction” of cancer cells to protein synthesis is stimulating efforts to exploit this as a druggable vulnerability. In addition, ribosomopathies are a devastating group of diseases caused by germline ribosome deficiency that substantially increase the risk of cancer in children and young adults (up to 40% in the 4th decade of life). In prior MRC-supported work, my lab determined that the SBDS protein that is deficient in the inherited leukaemia predisposition disorder Shwachman-Diamond syndrome (SDS), is crucial for maturation of the large ribosomal subunit. We defined SDS as a ribosomopathy that is caused by defective release of the anti-association factor eIF6 from the nascent large ribosomal subunit. However, the molecular mechanisms underlying this process remain incompletely understood. Our goal is to elucidate the basic molecular mechanisms of late cytoplasmic ribosome assembly to facilitate the development of novel treatments for ribosomopathies and cancer more broadly. A major barrier to progress has the lack of detailed structures of native pre-60S ribosome assembly intermediates, which are highly dynamic and often transient. We will fill this knowledge gap by leveraging ground-breaking technology developed in our lab to resolve ribosome structures to better than 2 Å using single particle cryo-electron microscopy (cryo-EM). This project demands a multidisciplinary approach, integrating structural studies with detailed molecular dynamics, biochemical, biophysical and genetic approaches. The timeliness and feasibility of this programme is supported by our published work and strong preliminary data.  Our central hypothesis is that a coordinated and dynamic network of protein-RNA interactions functionally proofreads ribosome quality during nascent 60S subunit assembly. We will address this hypothesis with the following specific aims: Determine how GTPase activation is coupled to structural rearrangements during 60S subunit maturation Determine mechanisms regulating entry of the nascent ribosomal subunit into active translation Determine mechanisms regulating eIF6 function Our discovery based Programme will provide a step change in understanding the biological mechanisms involved in ribosome assembly, build new capabilities in the field and help improve human health. The work addresses a clear unmet need to improve the quality of life and survival of patients affected by ribosomopathies. Furthermore, the results may be exploitable for cancer drug discovery. The programme fits within the MRC strategy of driving an integrated understanding of human disease, securing better health, ageing and wellbeing and is aligned within the Government’s Life Sciences Vision. The work involves a unique combination of structural biology, molecular dynamics simulations, biochemistry, cell biology and human genetics to make discovery-based basic scientific advances and supports the breadth and diversity of skilled people needed for the future research and development workforce.

UKRI Gateway to Research · FY 2025 · 2025-04

Cell shape is intimately linked to function and is often altered in disease. A precise control of cell shape is fundamental to a wide array of physiological processes, including embryonic development, tissue homeostasis, wound healing, and immune response. Cell shape defects have been implicated in numerous pathologies, from developmental disorders to cancer. Yet, despite its importance, our current understanding of cell shape control remains limited. This is largely due to the challenge of connecting molecular-scale interactions to the cell-scale mechanical forces that ultimately determine shape. This project focuses on the actomyosin cortex, a cellular cytoskeletal network that is a key determinant of cell shape. The cellular cortex supports the plasma membrane and comprises a thin layer of actin filaments, myosin motors and associated proteins. Myosin motors generate contractile forces within the cortex, which put the cortical network under tension. Cortex tension helps support cellular shape against external constraints, and gradients in tension drive cellular deformations in processes like cell division, cell migration, and tissue contractions. The cortex has been in the spotlight as a key regulator of cell shape for over a decade. Yet, our understanding of the regulation of cortical tension is very superficial, greatly limiting studies aiming to understand and perturb cellular shape. This poor understanding is in great part due of the technical challenges in imaging the dense and thin cortical network, which is typically under the resolution of classical microscopy techniques. As a result, the nanoscale organisation of the cortex, which ultimately determines cortex tension, remains mostly a black box. The proposed project aims to address these challenges by leveraging recent advances in super-resolution imaging and cryo-electron tomography of cellular structures. We propose to develop innovative imaging pipelines for quantitative analysis of the structural organisation of cortical actin and the arrangement and dynamics of cortical myosin motors. We will then use these tools to investigate how changes in actomyosin network architecture regulate cortical tension, focusing on mitotic cell rounding, a mechanical process of key importance for the success of cell division. Our central hypothesis is that changes in the nanoscale architecture of the cortex can trigger a switch-like increase in cortex tension. We speculate that such a structurally-triggered tension switch would provide a more robust and responsive mechanism for the control of cortical tension compared to tension regulation through gradual changes in myosin activity. We will explore this hypothesis using a combination of experiments and theory. By providing insights into the nanoscale organization of the actomyosin cortex, our findings will have wide-ranging implications for our understanding of cellular mechanics, potentially informing new therapeutic strategies for diseases linked to cell shape abnormalities, such as cancer and developmental disorders. Moreover, the imaging and analysis tools we propose to develop will be of broad interest in cell biology and biophysics, enabling further studies connecting the architecture of cellular cytoskeletal networks to their function. By bridging the gap between nanoscale cytoskeletal architecture and cell-scale forces, our study will shed light on how molecular interactions translate into macroscopic cell behaviours, illuminating fundamental principles of cell morphogenesis.

UKRI Gateway to Research · FY 2025 · 2025-04

The origin of livestock herding in eastern Africa dates to around c. 5000 BP and entailed a combination of demic migration of new populations into the region pushed southward as a consequence of increasing aridity at the termination of the early-mid Holocene pluvial; diffusion of domesticates and cultural practices, including new forms of burial, settlement, lithic technologies and ceramic styles and forms; and acculturation of some autochthonous hunting-gathering-fishing communities. Known as the Pastoral Neolithic, this phase of initial establishment and subsequent expansion across eastern Africa has attracted extensive archaeological interest, stimulated by advances in bioarchaeological, biochemical and geoarchaeological research, and higher precision radiocarbon dating. The ensuing Pastoral Iron Age, commencing c. 1200 CE, with the uptake of iron smelting technologies among herding communities, new ceramic styles, reductions in mobility, and changes in food production, has received much less archaeological attention. Yet, understanding these transitions and the factors that gave rise to them are critical for understanding the origins of many of the region's contemporary pastoralist communities, key cultural systems such as age-sets, and the socio-ecological viability and resilience of specialised pastoralism in the context of climatic uncertainty and periodic catastrophic regional droughts. The goals of this research are i) to provide, for the first time, an archaeological landscape and materials analysis of the origins and evolution of Pastoral Iron Age societies in north-central Kenya, through integrated analysis of patterns of human and livestock mobility, dietary practices, exchange networks, and responses to periods of known drought and increased rainfall over the last c. 1800 years, and ii) demonstrate the value of understanding these pastoralist pasts as paths for planning more sustainable futures for the region's contemporary pastoralist societies.

UKRI Gateway to Research · FY 2025 · 2025-04

Cosmologists have made remarkable progress in understanding billions of years of the Universe's evolution, but the first fraction of a second after the Big Bang is still mysterious. The details of what happened in this fraction of a second hold the key to some of the most fundamental questions in physics. Theorists have long thought that the Universe may have undergone one or more dramatic, discontinuous changes in this time, called first-order phase transitions, in which a field reaches a lower-energy state by nucleating 'bubbles' of a new phase. These transitions could solve a variety of cosmic puzzles, such as why there is more matter than antimatter, and whether our Universe is part of a larger 'multiverse'. For decades there was no way to empirically test these ideas, as the earliest light we can ever hope to observe with our telescopes was emitted more than 300,000 years after the Big Bang. That situation has changed with the recent advent of gravitational-wave astronomy, which allows us to observe signals from the very first moments of the Universe's history. First-order phase transitions are a powerful source of gravitational waves, and are thus a prime observational target for current and future gravitational-wave missions. However, there are serious theoretical challenges in modelling these transitions, as they occur in the strongly non-perturbative, out-of-equilibrium regime where our physical understanding is limited. These challenges mean that various existing approaches all fail to capture some of the crucial aspects of the problem, and as a result there are significant theoretical uncertainties in the resulting observational imprints, including gravitational waves. I will use two innovative new approaches to tackle this problem. The first is cold-atom analogue experiments, which can be used to create quantum fields in the lab that emulate the behaviour of fundamental fields in the early Universe, allowing us to study cosmic bubble nucleation empirically, in real time, and in a controlled and reproducible manner. The second is semiclassical lattice simulations, which (unlike existing simulations) capture the dynamics of bubble nucleation, and reveal new observable phenomena such as correlations between bubbles. Together, these new approaches promise to unlock valuable new insights into cosmic bubble nucleation. This will be an ambitious research program in which I will combine (i) theoretical modelling and interpretation for cold-atom analogue experiments, with the goal of extracting new insights on bubble nucleation from experimental data; (ii) establishing semiclassical simulations as a new tool for studying gravitational waves from phase transitions, by developing the necessary numerical frameworks and extending the simulation method to new physical regimes; (iii) translating these results into improved analyses of gravitational-wave data, and forecasts for future missions. I will complement this research with a program of public engagement and outreach, built around an interactive bubble-nucleation app that will provide an intuitive and engaging visual tool for communicating ideas about the early Universe. My public engagement work will target secondary-school children, particularly from groups that are under-represented in STEM, with the goals of inspiring interest in science and tackling educational inequality. As well as being crucial and timely for gravitational-wave cosmology, my work will provide insights into a broad range of questions about early Universe physics. I will also strengthen emerging links between the cosmology and cold-atom communities, helping to drive further progress in this fruitful new area of interdisciplinary collaboration.

UKRI Gateway to Research · FY 2025 · 2025-04

Animals integrate multiple sensory inputs, learn and remember past events, predict future ones, and combine current and past information to choose and coordinate appropriate motor responses. Underlying these capabilities is the nervous system, whose operational patterns depend on the synaptic-level structure of its neuronal wiring diagram, the connectome. While each individual is expected to have a unique connectome, a large fraction of its neural circuit architecture is shared across individuals. What fraction of an individual's connectome is conserved across individuals is unknown, as are the ways by which each individual differs from the common subset. Here, we propose to map the complete connectome of the whole nervous system of multiple individuals of the same species using electron microscopy and machine learning techniques, and then compare them to (1) identify the consensus connectome; (2) measure natural variability both across brain hemispheres and across individuals; and (3) identify hotspots of variability. This study will reveal a neural circuit basis for inter-individual differences and establish a baseline for cross-species comparisons of connectomes

UKRI Gateway to Research · FY 2025 · 2025-04

Context For the correct wiring of neural connections during development, bidirectional synaptic plasticity is required. Such bidirectional plasticity has been most thoroughly studied in the hippocampus, which displays both synaptic long-term potentiation (LTP) and long-term depression (LTD). Synaptic potentiation is present throughout life and is important for learning and memory processes, whereas it is assumed that synaptic depression is developmentally regulated and more important early in life when an excess of synaptic connections is pruned away. It is thought that synaptic depression is the first step in this activity-dependent process of selective synapse elimination. Project challenge Both LTP and LTD require NMDA receptors for their induction. The challenge addressed by this project is to understand how the same type of receptor can mediate opposite changes in synaptic weights. Three main explanations have been proposed: (1) different NMDA receptor subunit composition coupled to different signalling cascades, (2) different presynaptic versus postsynaptic location of the NMDA receptors, or (3) ionotropic versus metabotropic mode of signalling of the NMDA receptor. In this project we will focus on receptor location and mode of NMDA receptor signalling for induction of LTD in the mouse hippocampus. Aims and objectives It is well established that the induction of hippocampal LTP requires activation of postsynaptic ionotropic NMDA receptors. The aim of the proposed work is to test the hypothesis that induction of hippocampal LTD instead requires activation of presynaptic NMDA receptors. To test this hypothesis, we will use a combination of electrophysiology, molecular techniques and pharmacological manipulations. The first objective is to establish the presynaptic versus postsynaptic location of NMDA receptors required for the induction of two forms of LTD at hippocampal CA3-CA1 synapses. The second objective is to investigate whether these NMDA receptors signal via an ionotropic or metabotropic mechanism. Potential applications and benefits Synaptic plasticity is important for cortical circuit refinement in the developing brain as well as for learning and memory processes in the adult brain. The underlying mechanisms are of fundamental interest to basic neuroscientists. In addition, these mechanisms may be involved in disorders where synaptic connectivity is altered (so-called “connectopathies”). Researchers have increasingly recognised how synaptic plasticity gone awry in children and teenagers could lay the foundation for neurodevelopmental disorders, such as schizophrenia or autism. It may also be the case that some of the same plasticity mechanisms that normally help refine brain wiring early in life contribute to later pathological synapse loss in Alzheimer’s disease and other neurodegenerative disorders. If so, synaptic plasticity mechanisms could be a therapeutic target.

UKRI Gateway to Research · FY 2025 · 2025-04

Antimicrobial resistance (AMR) in infectious diseases is increasingly recognized as a severe threat to global public health. AMR occurs when bacteria, viruses, fungi, and parasites evolve to resist the effects of medications, rendering standard treatments ineffective and leading to persistent infections. This resistance is fuelled by the overuse and misuse of antibiotics, poor infection control practices, inadequate sanitary conditions, and the global movement of people and goods. Leprosy, a chronic infectious disease characterized by granulomatous lesions affecting the skin and peripheral nerves, is caused by the bacterium Mycobacterium leprae (M. leprae). In 2022, approximately175,000 new cases were reported globally, predominantly in tropical regions. Standard treatment involves a multidrug regimen consisting of Dapsone, Rifampicin, and Clofazimine, administered over a duration of six months to one year. Since the 1960s, resistance to individual drugs has been observed, and recent findings indicate the emergence of multidrug-resistant M. leprae strains. As an obligate intracellular pathogen, M. leprae cannot be cultured in axenic media, necessitating the use of molecular diagnostics for detecting AMR. These diagnostics typically involve extracting M. leprae DNA, amplifying drug target genes via polymerase chain reaction (PCR),sequencing the amplicons to identify mutations, and performing bioinformatics analysis to determine the impact of the mutations on drug interactions and activity. While effective, this procedure requires advanced molecular/genomics laboratories, which are often unavailable in resource-limited settings, such as those in Southeast Asia. Additionally, the complexity and duration of in-vivo testing, which spans 6-8 months, make it impractical for routine diagnostic applications.Therefore, rapid, and accessible molecular diagnostic tools are crucial for effective disease management in endemic regions. The Philippines reports nearly 2,000 new leprosy cases annually. The absence of a decentralized diagnostic system for AMR in leprosy necessitates the development of innovative tools to ensure timely diagnosis and management. Understanding the mechanisms underlying AMR in leprosy is crucial for clinicians to identify alternative treatment regimens for drug-resistant cases. Leveraging our expertise in point-of-care compatible DNA amplification and sequencing technologies (Biomeme qPCR and Oxford Nanopore MinION based amplicon sequencing), along with our expertise in developing and maintaining sophisticated bioinformatics workflows and tools (such as HARP and HANSEN web databases), we propose the following objectives: WP1: Comparative evaluation of Biomeme qPCR and MinION-based DNAsequencing with conventional qPCR and DNA sequencing for detecting mutations in drug target-coding genes (rpoB, folP, gyrA, rpoC, fadD9, ribD, and nth) conferring AMR in leprosy. WP2: Development of a bioinformatics pipeline/workflow for the analysis of DNA sequencing data, determining mutations, and predicting the impacts of mutations on drug target protein structure, drug binding, and interatomic interactions. WP3: Decentralizing diagnosis of AMR in leprosy using point-of-care Biomeme qPCR and MinION-based DNA sequencing technologies at regional hospitals in the Philippines. WP4: Knowledge transfer, training, and capacity building of laboratory staff at the Department of Dermatology, Philippine General Hospital, and the College of Medicine, University of the Philippines, Manila. By advancing these innovative diagnostic tools and empowering local health systems, we aim to improve the management of leprosy and mitigate the impact of antimicrobial resistance in endemic regions.

UKRI Gateway to Research · FY 2025 · 2025-04

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

UKRI Gateway to Research · FY 2025 · 2025-04

Context and topic of research The effective distribution of funds to sustain a productive and healthy research system is a key concern of funders and institutions. To achieve this, governments and research funders commission reviews and set out strategies examining micro- and macro-determinants of research productivity (e.g., CCA 2012, with an updated one in progress; DSIT, 2021; DSIT, 2023). An important, often overlooked factor, in these reviews is the institutional sub-structure and research group structure. For example, the organisational structure of the MRC Laboratory of Molecular Biology (LMB) has been suggested to be a key to producing high-quality scientific output (Nature, 2024). Large-scale quantitative bibliometric studies and small-scale qualitative studies of research collaborations and research group characteristics support the idea that organisational structure can affect the research produced: the relation between team size and citations and productivity (Fox 1991, Lee & Bozeman 2005, Shi et al. 2009); the relation between team size and hierarchy on the disruptiveness of its publications (Wu et al., 2019; Xu et al., 2022); and the relation between gender-diversity and ethnicity-diversity and the novelty and impact of research produced (AlShebli et al., 2018; Yang et al., 2022). Aims and objectives While bibliometric approaches are powerful for exploring collaboration patterns in academia, they conflate authorship lists and research group membership, with the former based on named authors on publications and the latter representing the environment researchers work in. Conversely, this issue is less present in qualitative studies, but they are unable to cover a wide and diverse range of groups. Here, we suggest a unique approach to explore the relationship between organisational structure and research output, by combining administrative, bibliometric, and qualitative data, covering both macro- (across entire institutions) and micro- (individual researchers’ experiences) level information, across two research institutions (the University of Cambridge and Université de Montréal). Unlike previous studies, we will use institutional administrative data to accurately define research groups and their composition and supplement it with bibliometric data to explore how the organisational structure of research groups (devolved/hierarchical, networked/isolated, small/large), structural dynamics (churn and growth rates) and demographics mixtures, relate to the groups’ research outputs, impact, and productivity. Through focus groups with a diverse stratified sample of research groups, we will explore the experiences of researchers in differently structured groups to elucidate how these relate to research production. By comparing internally available administrative data with externally available bibliometric and web-based data, we will develop means to approximate organisational structure using publicly available information allowing us and others to generalise this approach to cases where access to administrative data is not possible. Potential applications and benefits In contrast to previous studies examining authorship lists, this study will reveal the relationship between the structural organisation of research groups and research outputs; and the heterogeneity of these relationships across disciplines. This work will be supplemented by qualitative work to elucidate possible mechanisms underlying these relationships and help to identify key transition points in the structure of research groups which may need particular support. We will convene policy workshops with institutional and national stakeholders to contextualise our findings and develop policy recommendations, which we will publish in a policy brief. Our findings will help policymakers improve the productivity of research by taking into account the effects of research group organisation in different disciplinary contexts and for different objectives.

UKRI Gateway to Research · FY 2025 · 2025-03

Each fellowship will last up to 18 months to cover: a 3-month inception phase for set up activity a 12-month placement with the host organisation an impact phase lasting up to 3 months Fellows will co-design projects and activities with their host and produce analysis to inform government decision-making across a range of policy priorities. Fellows will also engage across the host organisation, building effective working relationships and supporting wider knowledge exchange with researchers. This will be supported through their embedded role within the host organisation, including line management support.

UKRI Gateway to Research · FY 2025 · 2025-03

This proposal is underpinned by our recent discoveries: out of plane ferroelectricity in hetero-bilayers of atomically thin body (ATB) semiconductors (Science, 2022); and realisation of wafer scale growth of a universal dielectric in the form of hexagonal boron nitride (h-BN) (Nature, 2022). The ground-breaking nature of the proposed work is in realisation of ultra-low power devices - namely ferroelectric field effect transistors (FeFETs) and tunnel electro-magneto-resistance (TEMR) devices - using industrially relevant complementary metal oxide semiconductor (CMOS) compatible processes that can perform both logic and memory functions to increase the energy efficiency of electronics. The carbon footprint (3% of total CO2 emission) of modern electronics is comparable to that of aviation and is expected to rise to ~10% by 2030 because of the von Neumann bottleneck where information is shuttled between the logic and memory devices, which increases energy consumption and reduces the processing speed. One objective of the proposed work is to directly explore and therefore understand the key processes that underpin the stable operation of FeFETs based on ATB semiconductors to significantly accelerate their development. Second objective is to integrate ferroelectric hetero- bilayers as tunnel layers between two ferromagnetic contacts to realise TEMR devices with magneto-resistance of > 1000%. The advantage of TEMR devices is that the tunnelling probability can be tuned with polarisation of the ferroelectric tunnel layer so that very large MR is achievable. In applications that are of strategic importance for the UK, energy efficient electronics are fundamentally important for meeting the net zero by 2050 goal as well as developing resilient local supply chain for semiconductors. We propose to focus on hetero-bilayers of transition metal dichalcogenide (TMD) compounds as a novel class of ferroelectric semiconductors where probing and understanding of device operation can rapidly improve the quality and control of available devices beyond the state-of-the-art, and for which recent work has highlighted significant application potential for high performance electronics. The motivation for such new devices is to address today's most important scientific challenges, namely that of climate change through energy efficient high-performance electronics. The recently published Nation Semiconductor Strategy highlights the need to develop the UK market and local supply chains. Atomically thin semiconductors were pioneered in the UK and this proposal will leverage the local expertise to develop new technology. Specifically, we aim to: (i) Develop methodology for realising ultra-clean semiconductor/dielectric interface using our recent breakthrough in high quality wafer scale chemical vapor deposition (CVD) grown h-BN (Nature, 2022) to eliminate hysteresis due to interface defects. We will also integrate our ultra-clean van der Waals (vdW) contacts on ATBs [enabled via EPSRC funded research (EP/T026200/1) and reported in Nature 2019, 2022] to eliminate defects at metal/semiconductor junctions. (ii) Establish a fundamental understanding of ferro-magnetic (FM) vdW contacts for spin injection and tunnelling behaviour through ATB TMD ferroelectric hetero-bilayers. (iii) Develop an integrated and scalable CMOS compatible fabrication process for ultra-low energy FeFETs and TEMR devices based on wafer scale CVD grown ATB hetero-bilayers using h-BN dielectrics and vdW contacts. (iv) Explore transport properties of FeFETs and TEMR devices that are capable of functioning as both logic and memory devices to establish understanding of fundamental operating mechanisms and energy footprint. Establish new design concepts exploiting the logic and memory functions of FeFETs and TEMR devices for high performance, low power electronics.