IMPERIAL COLLEGE LONDON

UKRI Gateway to Research · FY 2025 · 2025-06

Management of the Fukushima Daiichi Nuclear Power Plant, in the aftermath of the 2011 tsunami-caused accident, has now progressed to the stage where treated cooling water is intentionally being released into the ocean through an offshore discharge pipe. This release is planned, and due to elevated levels of certain low risk radionuclides, such as tritium, it can be effectively monitored through an extensive offshore monitoring campaign. However, partly due to the migration of untreated material on the surface and within the ground of the site, additional pathways exist through which more hazardous radionuclides can reach the broader (marine) environment. These can also be identified through the offshore monitoring campaign. These can be termed unplanned releases, and they pose a greater challenge in terms of identifying their sources and transport routes. At present there is little to no high-resolution marine modelling of the site covered by this extensive monitoring network. The underpinning vision for this new collaboration stems from this gap and the timely opportunity that the Fukushima power plant accident, its ongoing management and in particular the recent initiation of treated water discharge and associated data collection represents. Moreover, it stems from the belief that data without supporting models, as well as models without data to ground them, can be considered anywhere from being of questionable value, to being outright dangerous. Given the critical importance of addressing the release of toxic materials into the environment and acknowledging the current lack of detailed modelling and model-data fusion efforts, it is imperative that the research community supports this endeavour. Given operational/planned releases, decommissioning activities resulting in accidental unplanned releases, and ongoing decommissioning and nuclear new build efforts worldwide, including in the UK, this issue extends beyond the Fukushima site. The partnership proposed in this seedcorn project will thus contribute to new knowledge, tools and research that will generate broader important impact. The aim of this initial seedcorn project is to work with our international partner on the first proof-of-concept steps towards developing an innovative modelling and data integration framework to predict, understand, and identify the dispersion pathways of radionuclides within the marine environment. This new framework will yield a step-change in the simulation accuracy of near-shore marine transport through a range of advanced numerical techniques, building on unique computational methods that can maximise the value of available observational data as well as provide insight into optimal sampling and data collection strategies.

UKRI Gateway to Research · FY 2025 · 2025-06

This proposal addresses two key questions in space plasma physics: How is the three dimensional heliosphere controlled by the solar magnetic field? What is the structure of the near-Earth interplanetary magnetic field on the scale of the magnetosphere? For the first question, we will use new measurements from the Solar Orbiter spacecraft as it moves out of the solar equatorial plane from February 2025. No such measurements have been made within Earth orbit, but Orbiter will make scans between 18 degrees North and South, taking a month, every 5 months from April 2025. We will use these to map the latitudinal structure of the heliospheric magnetic field as it evolves and compare it to remote measurements and models. We will constrain these models, since there are major unresolved discrepancies in the existing data. We will combine our data with those of other spacecraft such as Parker Solar Probe and BepiColombo to show how the low latitude wind, including that near the Earth, is affected by that at higher latitudes. For the second question, we will again use new data: from the NASA IMAP mission launching in mid-2025, as well as others, which will give us for the first time six spacecraft measuring the solar wind and magnetic field in the upstream L1 halo orbit. By combining measurements from this constellation we will be able to measure the 3D structure of the magnetic field on the driving scale of the solar wind turbulence, around 100 Earth radii: this is vital for understanding how turbulence evolves in the solar wind since plasma turbulence is, unlike in hydrodynamics, greatly affected by how it is driven. We will also develop methods to combine data from all the spacecraft to make better predictions of the solar wind and magnetic field arriving at the Earth and its spatial variability, which is important as an input for understanding the dynamics of the magnetosphere. This work is timely given the spacecraft orbits and launches. We are ideally placed to undertake it, given our experience in both the near-Sun solar wind and multi-spacecraft analysis methods and our key mission roles (Solar Orbiter MAG Principal Investigator and IMAP MAG instrument lead).  

UKRI Gateway to Research · FY 2025 · 2025-06

Enhance the compute and storage provisions at the Imperial College IRIS cloud to increase support for IRIS Science Activities.

UKRI Gateway to Research · FY 2025 · 2025-06

Planets closer to their host star than Mercury are known to be abundant, with most stars hosting at least one. In this population, “sub-Neptune” planets (radii between ~2-4x the Earth’s) are the most abundant, yet they are the least understood. Their densities imply they host a large atmosphere dominated by volatiles; however, modelling degeneracies mean we cannot infer their compositions from measurements of their mass and radius alone. Observations of their atmospheres by HST/JWST and in the future by the ELTs and ARIEL are already opening up the possibility of constraining their composition. However, the vast majority of the exoplanets where we can and will study their atmospheres are billions of years old. Thus, understanding evolutionary processes that can change a planet's atmospheric composition is critical. Due to the proximity to their host stars, the extreme heating of these planets' volatile atmospheres can drive mass-loss via powerful hydrodynamic outflows. These outflows are theorised to drive the bulk properties of the close-in exoplanet population, sculpting it into the population we see today after billions of years of evolution. However, these outflows can cause the atmospheric composition to evolve. Despite these outflows being hydrodynamic in nature (where the average collisional mean free path is shorter than the atmospheric scale height), more frequent collisions between lighter species, such as hydrogen, mean heavier species may not always be perfectly coupled to the outflow.  This ``fractionation’’ process is known to have shaped the composition of the Solar System terrestrial planets early in their lives; however, due to the complexity that arises from the extreme heating and ionization in close-in planets, it remains poorly explored. Exploratory works have demonstrated that atmospheric escape not only drives the evolution of the close-in exoplanets' bulk properties, it also drives their compositional evolution, where quantities like the C/O ratio are expected to evolve. Using multi-species atmospheric escape models, we will simulate the detailed composition of escaping atmospheres for the population of sub-Neptunes for the first time. By combining these species-dependent mass-loss rates into an evolutionary model for the planet, we can follow an exoplanet's compositional evolution from birth to when we observe it today. Without our modelling, interpreting exoplanet spectra will be fraught with difficulty as it will be unclear whether trends in composition between different planets and across exoplanetary systems are imprints of formation or evolutionary processes.  Our work will directly address STFC’s challenges B3 and B5.

UKRI Gateway to Research · FY 2025 · 2025-06

“Kepler planets” – Earth to few-Earth sized planets, orbiting very close to their parent stars – are ubiquitous around both sun-like stars and M dwarfs, and appear to be a major outcome of the planet formation process. However, no concrete theory for their formation exists. To quantitatively understand how these small, close-in planets are forged from the discs of gas and dust girdling young stars, we must undertake a detailed investigation of the co-evolution of gas and dust in the inner regions of these discs, close to the star. To this end, we have already developed the most sophisticated numerical model to date of the steady-state structure of gas in the inner disc, including the effects of dust grains on the opacity, viscosity and chemistry. Building upon this, we propose to undertake time-dependent numerical simulations of the gas+dust behaviour in the inner disc, including 2D dust dynamics, the feedback of the latter on the gas dynamics, and grain growth and fragmentation. No such detailed simulations of the inner disc have ever been performed before. We will use the new state-of-the-art code cuDisc, developed in-house specifically to model the evolution of dusty discs, for this work. Our results will elucidate, for the first time, the critical initial stage of Kepler planet formation: how, where and when dust grains coalesce into planetesimals (10-100 km sized bodies; the building blocks of planets), in the inner disc region. This in turn will have crucial population-level implications for the compositional and atmospheric properties of Kepler planets, which can be validated against observations by new and upcoming facilities (e.g., JWST, ARIEL, E-ELT), and will also be invaluable for interpreting such observations.

UKRI Gateway to Research · FY 2025 · 2025-06

Laboratory Astrophysics: new accurate atomic data for astrophysics Vision: Cutting-edge astronomical observations are now producing spectra with unparalleled resolution across the infrared (IR), visible, and ultraviolet (UV), enabled by advanced telescopes such as JWST, VLT, HST, Keck II, Subaru, and UKIRT. These high-quality, expensively acquired, spectra are highlighting the critical necessity for laboratory atomic data of at least matching accuracy to ensure their meaningful interpretation. The inadequacy of large amounts of existing laboratory atomic data frequently emerges as the weakest link in observational analyses, with much atomic data stemming from experiments conducted over six decades ago using low-resolution instruments. In many cases, order-of-magnitude improvements in the accuracy of atomic data are required for the unambiguous identification of all features of interest in astronomical spectra. Astronomy heavily relies on the accuracy and abundance of atomic data, making it as crucial to progress in the field as observational instruments themselves. With the imminent operation of next-generation telescopes such as the ELT, the demands for precise and comprehensive atomic data are only set to increase. Atomic data play a pivotal role in deciphering the intricate line structures blended within astronomical spectra and form the foundation for reliable astronomical spectrum synthesis and chemical element abundance determinations. Theoretical calculations alone cannot yield atomic data with the requisite precision for these applications and laboratory measurements remain the sole source of sufficiently accurate data. Objectives:  In this research programme the Imperial College London (ICL) Spectroscopy group continues to take up the challenge of meeting this acute need by measuring and analysing atomic spectra of many astrophysically important elements. We specialise in high-resolution studies of transition wavelengths, energy levels, transition probabilities (log(gf)s, oscillator strengths, f-values), and line broadening effects, including hyperfine and isotope structure. Using high-resolution Fourier transform spectroscopy (FTS), from the infra-red to vacuum ultraviolet, we will continue to significantly advance the quality and quantity of atomic data, achieving substantial reductions in uncertainties for transition wavelengths and energy levels, often exceeding an order-of-magnitude in improvement, and measuring transition probabilities accurate to just a few percent. The high resolution of FTS also enables us to determine line broadening effects such as hyperfine and isotope structure, crucial data for accurate stellar abundance measurements. The accuracy of the atomic data produced by the ICL group meets and exceeds the requirements of modern astrophysical analyses. Our new atomic data is incorporated into databases and model atmosphere codes, benefitting astronomers worldwide.

UKRI Gateway to Research · FY 2025 · 2025-05

The sustainable generation of green hydrogen is a critical challenge in our transition towards net zero. Artificial photosynthetic systems based on photocatalytic particles in suspension offer one of the potentially lowest cost routes to green hydrogen production using sunlight. However the limited visible light absorption of most photocatalytic systems to date, typically based on metal oxides, has to date limited achievable conversion efficiencies. Recently, substantial breakthroughs have been achieved in the performance of photocatalyst particles based on organic semiconductors, harnessing solar light across the visible and near infrared. However to date efficient hydrogen generation has only been achieved in the presence of sacrificial electron donors. In this project, we will focus on the development of organic heterojunction photocatalysts with controlled nanomorphology and their integration into a hybrid organic / inorganic tandem system for green hydrogen synthesis from water without any sacrificial species. The project brings together the expertise of the Durrant group at Imperial in the spectroscopy and photochemical function of photocatalytic systems with the McCulloch group's expertise in the design and synthesis of organic semiconductors. It further benefits from the participation of two talented researcher / co-investigators, Dr Soranyel Gonzalez Carrera (Imperial) with expertise in nanoparticle processing and photocatalytic characterisation and Dr Catherine Aitchison at Oxford with expertise in templating strategies for organic photocatalysts. The project will focus on the synthesis, characterisation and optimisation of visible / near IR absorbing organic heterojunction photocatalyst nanoparticles. Optimised nanoparticles will be tested in a tandem Z-scheme configuration with facet engineered Bismuth Vanadate particles supplied by our project partner, Prof Can Li from the University of Dalian, in order to achieve overall water splitting. Two strategies will be explored to fabricate heterojunction nanoparticles: i) blended organic heterojunction nanoparticles of selected donor polymers matched with molecular acceptors, using our established nanoemulsion solution processing technique and ii) templated covalent organic framework heterojunctions formed through our novel templating technique of D/A polymer sheets. Both systems will be functionalised with a molecular proton reduction catalyst to maximise selective proton reduction to H2, with nanomorphology and surfactant control used to optimise selective oxidation of a reversible FeII/FeIII redox couple. A core element of this project will be in-depth photophysical characterisation on timescales from fs to seconds, allowing us to determine the timescales of charge separation, recombination, and transfer to the proton reduction catalyst and FeII/FeIII, enabling iterative optimisation of each of these steps and thereby overall photocatalytic performance. Optimised photocatalysts will be selected on the basis of their efficiency for hydrogen generation and their stability, and then integrated into an overall water-splitting Z-scheme system with the BiVO4 water oxidation photocatalysts. The project has thus three specific objectives: -Development of organic semiconductor heterojunction photocatalysts with optimised (nano)morphology, high (photo)stability and selective proton reduction / FeII oxidation -In-depth mechanistic studies using advanced transient optical spectroscopies to identify the key performance descriptors and iterative materials design guidelines. -Optimisation in a Z-Scheme tandem system by integrating organic heterojunction photocatalyst for hydrogen evolution with BiVO4 oxygen evolution photocatalysts using a redox couple to achieve overall water splitting with STH efficiency of >1 %.

UKRI Gateway to Research · FY 2025 · 2025-05

The ability to prepare new molecules is crucial to address major societal challenges, including the development of pharmaceutical drugs. The pharmaceutical industry has repeatedly called for improved streamlined synthetic methods and new bond forming processes to aid discovery and development of drug molecules. To minimise environmental impact, chemistry must increasingly be performed catalytically, where a small amount of catalyst transforms a large amount of starting materials to products. A leading catalytic technology for complex molecule synthesis is known as 'C-H functionalisation'. This selectivity converts carbon-hydrogen (C-H) bonds into much more valuable linkages such as carbon-carbon bonds, to build a desired molecule. Furthermore, to ensure appropriate interactions with biological systems, synthetic methods must control the 3D shape of molecules. Heterocycles are carbon-based ring structures that contain at least one heteroatom in the ring (i.e. an oxygen, nitrogen or sulfur atom). They are crucial components in medicines. This research will develop methods for the 'C-H functionalisation' of heterocycles. Furthermore, this will be 'enantioselective' i.e. will control the precise 3D location of the reaction to produce only one of the two mirror image forms. High value heterocyclic products useful in the discovery of new drugs will be prepared directly from simple, readily available precursors. The developed methods will aid in divergent synthesis of the collections of compounds required in drug discovery and will present an intuitive synthetic disconnection option for medicinal chemists to accelerate drug discovery and development. Specifically, this research will: - Develop methods for exquisite control of 3D shape by selective functionalisation of a precise unactivated C-H bond on heterocycles and study the mechanism by which this can occur. - Develop more streamlined methods to achieve enantioselective C-H functionalisation on heterocycles, by using existing, common and useful functionality to form a 'transient' directing group. This will further reduce the required synthetic operations to generate the valuable heterocyclic products. - Prepare screening collections of compounds, as well as develop the synthesis of analogues of known drug compounds in a divergent manner. - Develop compounds as reactive mirror-image pairs, using the developed methodology, that will be useful in screening efforts in drug discovery and in developing our understanding of biological systems. Overall, this research will develop new synthetic and catalytic methods for the generation of enantioenriched heterocycles that can be widely applicable in fields of chemical synthesis and medicinal chemistry to accelerate the development of new therapeutics.

UKRI Gateway to Research · FY 2025 · 2025-05

Dementia leads to cognitive impairment that impacts progressively on activities of daily living, erodes independence and impairs quality of life. The impact on individuals living with the disease, as well as on the NHS, is enormous. Technology has the potential to improve the lives of people living with dementia, but often a generic approach is taken that produces inappropriate and burdensome technological solutions. This approach often fails. To avoid this, we need to take intoaccount the particular needs to people affected by dementia and place them at the heart of the development process. Multidisciplinary teams need to come together in a coordinated way to develop, validate and integrate new technologies with existing dementia care to improve the quality of life of those affected by dementia. Our vision is to create a pioneering network dedicated to bringing together teams to develop zero or low burden, sustainable technologies that support independent living and improve quality of life for people affected by dementia. The network will promote interdisciplinary collaboration and knowledge exchange. We will focus on developing technology solutions that integrate with existing dementia care, are sustainable, and that can be deployed across diverse populations. We want to minimise the burden of technology and use it to empower individuals and their caregivers. Our overarching goal is to foster independence, improve quality of life, and ensure equitable access to innovative care technologies across diverse communities. The work of the network will focus on five key areas of dementia care need: mobility, communication, activities of daily living, health monitoring, and carer support. Within each theme our initial work will be to define where technology might have the biggest impact, building on the views of those affected by the disease. Guided by the technology priorities we have defined, we will provide funding for a range of projects that develop, validate and evaluate new technologies. Cross-cutting capabilities within the network will provide support for project management, PPIE/Co-production, device technology, software engineering, and data science/AI and scalability. We aim to maximise the use of data collected by integrating health and care data from multiple sources. Advanced machine learning methods will be used to uncover insights into health risks, care inequalities, and digital exclusion. Data will be used to inform timely, place-based, person-centred care. We will particularly focus on the co-development and promotion of low-cost, green technologies to ensure long-term feasibility and accessibility. This will include the use of energy-efficient materials and processes, as well as designing for long-term durability and minimal environmental impact. We will develop scalable technologies that can be rapidly deployed and linked across diverse geographical locations, demonstrating proof of principle for broad application. Our network will work to assemble and support teams to deliver technology solutions for the most important dementia care problems. We have brought together a core multidisciplinary team of investigators with expertise in computer science engineering, synthetic biology, neuroscience, and clinical dementia who bring diverse skills to this problem. In addition, we have the enthusiastic engagement of a range of network partners from health and social care, the third sector, industry, dementia research and dementia charities. We envisage the network will grow if awarded to provide a dynamic and representative group of the stakeholders necessary to produce a rapid impact on dementia care.

UKRI Gateway to Research · FY 2025 · 2025-05

Context and challenges: Physical examinations can contribute up to 20% of the data necessary for the diagnosis and management of a patient. Since this phase of diagnosis involves the judgement of the physician based on touch, visual, and auditory information from a wide range of patients, the reliability of diagnosis heavily depends on the proficiency of medical professionals, which can vary. This inconsistency can lead to Missed Diagnosis Opportunities (MDOs) and errors, contributing to clinical negligence claims which cost the NHS over £2 billion annually . Unfortunately, students have limited opportunities to practice physical examination techniques on real patients and rely on mannequins or humans with no pathologies for learning. There are limitations to present a wide range of scenarios using these methods. Potential applications and benefits: We are developing an innovative interactive medical simulation system designed to help medical students to learn and practice crucial physical examination skills, particularly palpation. This portable and accessible simulator can give students exposure to a variety of pathologies and patient scenarios before they begin clinical practice, reducing the need to "learn on the job." The medical simulation system is made of two components: a soft robotic haptic-enabled computer mouse (based on ‘Physical Pixel’ concept), and reactive ‘Virtual Patient’ software. The novel and beneficial aspects include: The ‘Physical Pixel’ concept which involves mimicking the physical properties of the abdomen at the location of the cursor on the Virtual Patient, enabling students to engage in realistic, hands-on training using a device smaller than the exploration area. Combined with the Virtual Patient which provides real time indentations and force reactions, a strong correlation to the real palpation scenario is created. Our new approach to haptic technology offers a direct, tactile experience by physically altering the device’s properties instead of actively simulating touch effects through vibration or restraint, allowing users to experience barehand interaction with the patient phantom. Real time stiffness control is achieved through novel, patentable mechanisms. The mixed-mode hardware and software approach offers versatility in pathologies and patient types, tuneability to meet all teaching needs, decreased costs by using standard computer screens, easier storage, and objective feedback on performance which is a rare and useful feature in this type of learning. The data collected during use is analysed to provide users with a detailed breakdown of their palpation performance, and this large-scale data collection from all users can be used to understand more about how physicians palpate in general and continuously improve the training techniques. Aims and Objectives: To date, we have created multiple working prototypes and completed initial tests with medical students to evaluate how well they adapt to and learn a simplified palpation method with the simulator. However, our crucial gap in development is validation that our technology is able to present real pathologies for a physician to diagnose with their existing palpation technique and knowledge. To achieve this, we plan to conduct three design iterations. Each iteration will be tested by medical professionals to determine whether their diagnoses align with the programmed scenarios for various pathologies and symptoms, including tenderness, rigidity, muscle guarding, masses (such as cysts and hernias). This 8 month project will allow us to move forward confidently with our product, ready for final testing and commercialisation.

UKRI Gateway to Research · FY 2025 · 2025-05

Pulmonary arterial hypertension (PAH), a rare condition in which the blood vessels of the lungs become narrowed, remains an unmet clinical need. UK national audit data show that patients still die prematurely of right heart failure (40% mortality at 5 years). The currently available treatments help relieve some of the symptoms but none as yet have been shown to change the underlying disease process. The introduction of sotatercept into the UK later next year may improve patient options but it is an injectable with ongoing questions about safety. Neither doctors nor patients consider it to be the final solution for PAH. Many researchers think that a major feature of PAH is mitochondrial dysfunction. Mitochondria are often referred to as the 'powerhouse' of the cell because they provide the cell with energy. The function of mitochondria in cells from PAH patients is impaired. We have identified a drug (emapunil) that binds a protein on mitochondria called The Translocator Protein (TSPO) and improves mitochondrial function in cell and animal models of pulmonary hypertension. TSPO levels are increased in the lungs of patients with PAH. Emapunil has been given to humans but not to patients with PAH. Here we propose using it as a tool compound to provide proof-of-concept that targeting TSPO in PAH reduces pulmonary artery pressure and measures of pulmonary vascular health and right heart workload and may offer a novel approach to treating the condition. There are two main parts to the study. Part 1: We have used positron emission tomography (PET) scanning to demonstrate that emapunil binds to TSPO in the lungs of healthy volunteers when given at a dose we know to be well tolerated. In Part 1 of the study we will use PET scanning to determine the optimal dose regimen (how much and how often emapunil needs to be given) to ensure that it binds to lung TSPO over a 24 hour period. Part 2: Once we have established the dose and dose frequency in Part 1, we will treat a small group of PAH patients with this dose regimen. We will recruit patients from a cohort in the UK with implanted devices (CardioMEMS, to measure pulmonary artery pressure, and LINQ, a heart rate-activity recorder) that report daily physiological measurements remotely. We will treat the patients with emapunil for 6 weeks, and then continue to monitor them for a period after we stop the drug. A beneficial effect that persists after the drug is washed out from the body will provide evidence that the it is modifying the disease. We will also measure glucose uptake by the heart at the end of treatment with emapunil to evaluate how hard the heart is having to work. The study is expected to provide data to encourage follow on investment to take emapunil forward into a larger phase 2 study, with the prospect of developing an orally administered drug with a novel mechanism of action that alters the course of PAH. External capital investment and further development of emapunil as a treatment could be triggered by any one of the following: (i) A dose regimen of emapunil that produced sustained binding of TSPO in the lung; (ii) A clinically significant reduction in resistance to blood flow through the lung; (iii) the demonstration that emapunil reduces right heart workload.

UKRI Gateway to Research · FY 2025 · 2025-05

Background Traumatic brain injury (TBI) impacts around 68 million individuals globally and stands as the primary cause of death and lasting impairment among those below 40 years old. Half of patients with moderate-severe TBI have persisting symptoms 6 months post-injury, with negative reports of long-term health and overall quality of life. These individuals often encounter disruptions in body regulation, indicating issues with the autonomic nervous system (ANS), a network of nerves that maintain heart rate and breathing rhythm. ANS dysfunction can lead to dizziness and balance problems in about half of TBI patients, significantly increasing the risk of falls. Moreover, research indicates that certain individuals who have experienced TBI are predisposed to falls because they encounter challenges in identifying symptoms of dizziness or imbalance, thereby increasing their susceptibility to falling. This increased fall risk is associated with a higher chance of long-term disability and premature death, underscoring the critical need for awareness among these patients regarding their body changes. In research, we know that problems with balance and the body's automatic functions separately affect people with TBIs. However, we predict that when both systems are dysfunctional the risk of falls will increase in multiplicative manner. Aim: To understand the mechanistic overlap between the vestibular and ANS in affecting postural control and to ultimately develop targeted and personalized treatment to reduce falls in TBI survivors. Objectives: (i) neuroimaging to identify regions affected by TBI that may impact ANS and vestibular function (ii) behavioral testing of objective ANS and vestibular function independently and simultaneously in 80 patients; (iii) collect autonomic and vestibular subjective symptom scores, including linked quality of life questionnaires and assessment. Objective 1: Conduct detailed brain MRI scans to assess changes in brain structure related to traumatic brain injury (TBI). Our main goal is to see if there's an association between these structural changes in the brain and issues with the body's automatic functions and balance. Objective 2: Using the same group, we will assess the change in blood pressure with lying in supine to standing and then again with vestibular system activation. We expect a rise in blood pressure with healthy participants and a drop in the TBI cohort. We hope to detect any abnormalities that might cause sensations of dizziness or unsteadiness. Objective 3: Collect quality of life information. Our aim is to grasp how disturbances in their body's self-regulation influence their overall well-being. We're interested in whether they experience increased falls and find it challenging to resume participating in their community or social activities after their injury. All evaluations will be conducted 3-4 months post injury. Impact: TBI survivors suffer from chronic imbalance that worsens both quality of life and longevity, primarily via falls. ANS and vestibular dysfunction are independently linked to falls, however vestibular-ANS overlap and associated brain mechanisms has never been assessed previously. This project will reveal this overlap and enable interventions to treat these under-investigated clinical manifestations of TBI.

UKRI Gateway to Research · FY 2025 · 2025-04

To improve activity levels in the UK population, the NHS promotes running through its 'couch to 5k' program. Running is a great exercise, but the downside is the risk of injury which can happen to everyone, from beginners to pro athletes. The most common injury is knee pain and women are twice as likely to experience it than men. Many studies report that exercising two of the hip muscles (the gluteus maximus and tensor fasciae latae) is the most effective way to improve knee pain. This is because these hip muscles are connected to the knee by a stiff band of tissue that runs down the outside of the thigh (the iliotibial band). The anatomy of this band of tissue is well known, but we don't know how it works, we don't know which parts of the band pull tight when either of the hip muscles are tensed, nor which part of the knee is affected by which hip muscle. The aim of the project is to find this out. To give us new understanding on how the hip muscles affect the knee joint we will take a three pronged approach. (1) We will create an experimental cadaver model that can actuate the hip and knee muscles. We can then elucidate how the iliotibial band is tensioned by the hip muscles and how this tension is transferred to the different parts of the knee. (2) We will create a computational model with a new iliotibial band contribution based on the findings from the experimental model and calculate the kinematics for a wider range of simulated activities than is feasible experimentally. (3) We will validate the experiment and computational model by measuring strain in the iliotibial band in healthy volunteers using an ultrasound approach recently developed in our lab. Success in the three methods outlined above will lead to new understanding on how the hip muscles affect the knee joint. This will benefit researchers in the physiotherapy, surgical and musculoskeletal modelling field, it will lead to more precise rehabilitation and preventative exercises for knee pain. The ultimate beneficiary will be people who seek to maintain an active lifestyle and are affected by knee injury. The research is thus timely because this aligns with the current NHS initiatives to increase the health of the nation outlined at the beginning of this summary.

UKRI Gateway to Research · FY 2025 · 2025-04

Each year in the UK, more than 49,000 people are diagnosed with lung cancer and around a quarter contain mutations in the KRAS gene. Once considered 'undruggable', KRAS can now be targeted by advanced therapeutic approaches such as mRNA based personalised vaccines that can train the immune system to recognise mutated proteins (neoantigens) and eliminate the cancerous cells harbouring them. However, mRNA vaccines are typically injected into the skin or muscle but it has shown that for lung immunity, local delivery to the airway may enhance long-term protection. Delivery of mRNA to the airway faces many hurdles including formulation stability, mucosal clearance and barrier function of the lung which acts to expel inhaled materials. Consequently, airway delivery of personalised cancer vaccines has not yet been demonstrated. We have previously developed biodegradable polymeric vectors that enabled the first nebulisation of mRNA to the airway. To improve potency and reduce mucosal clearance, we have built on this platform to generate prototype peptide modified materials to bind to receptors in the lung and have shown enhanced mRNA delivery in barrier epithelium of reporter proteins compared to unmodified polymers. To progress our technology towards clinical application, we propose to deliver mRNA encoding mutated KRAS with the peptide-polymers in an airway delivery platform. The airway plays an important role in immune regulation, functioning as sentinel immunoregulators providing an excellent therapeutic target for our technology. The proposed work in this grant will be critical at this early stage to validate the peptide-polymers for; 1. Production of mRNA encoded neoantigen production in vitro and correct presentation. 2. Generation of antigen specific antibody response in vivo following airway delivery Achieving these defined aims will increase technology readiness level by confirming that mRNA encoded neoantigen presentation is possible our airway delivery platform  and move towards a specific clinical application. The MRC Developmental Pathway Gap Fund provides an appropriate framework to de-risk the technology for future funding to investigate efficacy in lung cancer models for further product development.

UKRI Gateway to Research · FY 2025 · 2025-03

The purpose of this grant is to continue support for PATT linked travel by members of the Imperial College Astrophysics Group to PATT approved telescopes for the two year period starting 1st April 2025.

UKRI Gateway to Research · FY 2025 · 2025-03

Over the last century the Arctic has been warming three times faster than the Earth as a whole. Inferences from ice core records imply that the warming rate in Antarctica is also faster than the global average. These rapid changes are already having major a socio-economic impact locally within the high latitude regions (e.g. food and water security) and through their remote influences (e.g. extreme weather). These impacts are predicted to intensify with time. However, current climate models fail to capture the observed rate of polar warming while predictions of future high latitude climate show significant model to model variation, severely limiting confidence in our ability to plan for and mitigate future change. The amount of warming primarily depends on the overall balance between the incoming solar (shortwave) and outgoing thermal (longwave) energy. Although there is conjecture as to the dominant physical mechanisms at play, accelerated high-latitude warming is strongly influenced by processes involving longwave energy flows. Ice and mixed-phase clouds are particularly prevalent at these high latitudes and exert a strong control on these energy transfers. Cold surface and cloud emitting temperatures mean that more than 60 % of this longwave energy is located at wavelengths longer than 15 microns in the so-called ‘far-infrared’. Despite its energetic importance, observations of the far-infrared energy spectrum are severely lacking. For example, we have only a handful of measurements of the surface thermal emission at these wavelengths while observations of the outgoing far-infrared energy spectrum from space are only just being realised. Such measurements, in combination with in-situ observations characterizing the surface and atmospheric state, are critical for testing and improving key components of the large-scale models used to predict our future climate. CLEFCC will exploit a unique set of observations from two field campaigns, designed to deliver the measurements we so urgently need. Coupling these with ground-breaking satellite observations of the Earth’s outgoing longwave spectrum, we will focus on three critical questions: (1) Do current representations of surface properties capture the longwave emission spectrum of snow and ice surfaces correctly? (2) Is a new light-scattering model able to reconcile ice cloud microphysics (ice crystal sizes, shapes) with energetic (radiative) impact across the longwave spectrum? (3) Can our radiative transfer models successfully match simultaneous observations of the longwave energy spectrum at the surface, within the atmosphere and at the top of the atmosphere under a variety of different atmospheric and surface conditions?  In each case, should we obtain a negative answer to the question posed we will use the observations to inform us how to refine the underlying assumptions in our models to achieve closer agreement. The project brings together world-leading experts in Earth Observation, climate modelling, and light scattering and radiative transfer from the UK and US. It will deliver new, observationally evaluated tools for immediate use by the wider climate modelling and remote sensing communities. For example, our thoroughly tested ice-cloud optical property model will be well placed to become the globally leading tool for those working to derive ice cloud microphysics from satellite observations. Further, we anticipate that our results will motivate improvements in the treatment of surface-atmosphere energetic coupling and the representation of ice-clouds across the climate modelling community, both critical to enhancing confidence in our ability to predict polar, and therefore global, climate.

UKRI Gateway to Research · FY 2025 · 2025-03

Epidemiological surveillance is of crucial importance to monitor a population's health and to efficiently prioritise healthcare resources. Surveillance methods need to deliver unbiased estimates of local health metrics (in space and time) and to detect meaningful departures from expectation that can trigger consideration of a focal public health response. The COVID-19 pandemic has highlighted the importance of combining community surveillance with traditional diagnostic health data, at the same time flagging the need for a validated method to integrate these sources. This project will build a public health surveillance framework that employs advanced statistical methods to synthesise multiple data sources. It will make use of the ever-increasing healthcare data available in the UK, collected through administrative registries (e.g. hospital admissions and deaths), randomised surveys, as well as through syndromic sources such as GP prescriptions and visits, 111 calls, symptoms apps. Additionally, wastewater monitoring was extensively used as an economically efficient method to monitor COVID-19 circulating in communities and has the potential of being a key component in an integrated surveillance system. However, the concentration of contaminants in wastewater can be affected by population characteristics that vary in space and time, as well as by changes related to the shedding of the viruses. Consequently, while some studies have established an association between aggregated wastewater and clinical measurements (e.g., lateral flow tests), this relationship has been shown to vary over space and time, to be non-linear and likely disease-specific. We will build a modular framework where each data source will be modelled within a module to account for uncertainties and potential biases. This collection of data modules will then be linked probabilistically so that all available data will contribute to the estimation of the underlying disease process. This in turn will provide vital information (for instance number of new cases) to inform where and when additional sources need to be swiftly deployed to reduce the burden of one or more diseases on the health system and on the population (e.g. how many hospital beds are needed or if specific interventions need to be put in place to reduce the disease burden). We will pay particular attention to the modelling and the utilisation of wastewater data within our multiplex system to inform the debate about the added value of using environmental surveillance in combination with traditional epidemiological metrics to form new indicators to answer surveillance questions. We will focus on disease-specific case studies (e.g. COVID, norovirus) to test and optimise the proposed surveillance framework but our ambition is to extend and operationalise the proposed framework to monitor an evolving suite of pathogens/diseases that might be at risk of becoming a public health threat.

UKRI Gateway to Research · FY 2025 · 2025-03

Abstracts are not currently available in GtR for all funded research. This is normally because the abstract was not required at the time of proposal submission, but may be because it included sensitive information such as personal details.

UKRI Gateway to Research · FY 2025 · 2025-03

Depression is the most prevalent and costly of all mental health disorders affecting up to 1 in 6 people in their lifetime and often results in suicide. Despite decades of research it has not proved possible to pinpoint a specific cause of depression in the brain of any particular patient. Doing this could be a major breakthrough that would help direct research towards new interventions as well as the selection of the best type of treatment for a particular person. The lack of a personalised biology of depression has led some to criticise the very idea of depression as a psychological disorder and even to claim that treatments such as antidepressants should not be used. The best-known hypothesis for the biology of depression is the serotonin deficiency theory - serotonin being one of the key messenger molecules in the brain. This argues that some cases of depression are caused by a relative deficit in serotonin function in part(s) of the brain that regulate mood. Apart from some early post-mortem studies that revealed lower levels of serotonin in the brains of patients with depression all the evidence to support this theory has been indirect, e.g. from the efficacy of antidepressant medicines that enhance serotonin, the fact that depleting serotonin leads to depression relapse and that deficits in serotonin production increase vulnerability to depression. Until recently it has not been possible to directly measure serotonin release in living human brain. We have worked for several decades to achieve this goal and recently published our methodology which uses a newly invented radioactively-labelled tracer molecule for a serotonin receptor subtype together with administration of d-amphetamine as a serotonin releasing agent. The brain distribution of the tracer before and after presence of the d-amphetamine can then be measured using PET - a highly specific molecular brain scanning technique. This approach gives a measure of serotonin release provoked by d-amphetamine for each person that we call the serotonin release capacity. Then with MRC funding we used this technique in depressed people and found that on average their serotonin release capacity was reduced. This provided the first direct evidence of a serotonin deficiency in the brain that could explain depression and why antidepressants that enhance serotonin such as the SSRIs (serotonin selective re-uptake inhibitors) work. The current grant is designed to provide independent replication of these findings using the specific and selective serotonin-releasing agent dl-fenfluramine that has just become available for human use. This will avoid the possibility that our previous finding with d-amphetamine could be due to the fact it also releases dopamine and noradrenaline, two other important neurotransmitters that may also be deficient in depression. A further benefit of the current study is that the group of depressed patients in which we measure serotonin release capacity will then be started on SSRI treatment after their PET scans. This will allow us to test if their improvement / lack of improvement to this serotonin promoting antidepressant treatment is predicted by their release capacity - with the hypothesis that those with lower release capacity will do better on the SSRI. If we succeed then it may prove possible to develop imaging methods to determine which patients would best be treated with SSRIs and which may require other treatment approaches.

UKRI Gateway to Research · FY 2025 · 2025-03

Abstracts are not currently available in GtR for all funded research. This is normally because the abstract was not required at the time of proposal submission, but may be because it included sensitive information such as personal details.

UKRI Gateway to Research · FY 2025 · 2025-03

The Large Hadron Collider (LHC) at CERN will be the world's highest energy particle accelerator for the foreseeable future, and the only facility capable of investigating some of the highest priority topics in fundamental physics. The UK has made a substantial long-term commitment to the design, construction and operation of the CMS detector, one of the two general-purpose detectors at the LHC. LHC operation will continue until at least 2035, with ever-increasing performance required from both the accelerator complex in order to provide useful statistical reach. The CMS detector will in turn require significant and comprehensive upgrades in order to maintain performance in the presence of much harsher conditions. The upgrades described in this proposal are mandatory to allow scientific return from the LHC to continue in the long term. We propose a technically ambitious five-year project from 2025 that will complete deliver of state-of-the-art tracking, calorimetry and trigger capabilities for CMS. These improvements will permit an order of magnitude increase in the recorded data set, allowing measurement of Higgs couplings and self-couplings, and greatly enhanced sensitivity to physics beyond the Standard Model.

UKRI Gateway to Research · FY 2025 · 2025-03

Pulmonary aspergillosis is a severe lung infection due to a green mould called Aspergillus fumigatus. We all inhale between 100 and 1000 Aspergillus spores daily, which can cause infections with mortality of around 40%, mostly in people with chronic lung diseases or weakened immune systems. There are estimated to be 4 million cases of pulmonary aspergillosis globally per annum, but very little is known about rates in South-East Asia. Antifungal resistance to the main class of drugs used to treat these infections, the triazoles, is rising. Environmental resistance rates of up to 90% have been detected in Vietnam, and 30% in Thailand. Resistance has been shown to double mortality. Work in Europe has shown that the increase in resistance is due to dual-use effects of triazole fungicides used in agriculture, as fungi are major crop pathogens. Resistant strains of Aspergillus fumigatus are emerging in the environment and causing infections in patients. As a consequence, the pharmaceutical industry is developing novel antifungal classes, however equivalent fungicides with the same mechanism of action are now being developed, and cross-resistance has been shown to occur experimentally. Fungicide usage is rapidly escalating in South-East Asia, but whilst composting has been identified as a major amplifier of azole-resistant Aspergillus fumigatus (ARAf)  in Europe, composting is not routinely performed in South East Asia. However the higher temperatures in this region mean that amplification may occur independently of compost. Therefore understanding the agricultural drivers  and hotspots for amplification of Aspergillus resistance and the impact on human health in South East Asia is urgently required. This will allow us to develop rational interventions to mitigate the risk of high mortality pulmonary aspergillosis infections whilst ensuring that food security is not compromised.   Aims 1: Develop novel point-of-care technologies to enable field testing for fungicide concentrations and  levels of ARAf in South East Asia We will use low-cost  “Delta Traps to sample air and “eco sensors” to capture water samples from soil. Fungicides will be detected using innovative point-of-care tests and ARAf identified using portable DNA tests. Techniques will be validated using Mass Spectrometry and Metabarcoding. 2: Field studies in Thailand, Vietnam and Laos to determine the extent of antifungal usage in the environment and the relationship to ARAf. Capacity building in local laboratories at specific hub sites in Bangkok, Hanoi and Vientiane to enable field testing and accurate diagnosis of pulmonary aspergillosis. We will then undertake field studies across one health aimed at understanding the extent of rural and urban anfungal use in the environment, the relationship to ARAf in the environment, the burden of pulmonary aspergillosis and the degree of resistant infections 3: Develop an appropriate interventional strategies to try to mitigate the risk of ARAf. We will assess local practices for fungicide use, undertake further experimental work to better understand the safe levels of fungicide usage in the environment. The evidence we generate will enable us to engage the agricultural industry, end-users, and policy makers to develop just interventions to mitigate the risk of ARAf. Together, these studies will deliver training and capacity building for South East Asian partners to be able to track Aspergillus resistance, identify its underlying causes, and be able to determine the impact of resistant Aspergillus infections on human health. A international framework will be developed to tackle the underlying causes.

UKRI Gateway to Research · FY 2025 · 2025-03

We propose to do this molecular classification in 400 severe asthma patients who will be observed over a one-year period in several centres specialising in treating patients with severe asthma in both UK and Korea. We wish to see what type of asthma and what diagnostic biomarker measured in the blood or in the exhaled breath that can tell us with great accuracy who will respond well to treatment with the antibody treatments that we have at the moment such as the anti-IL5 or anti- IL5Ra or anti-IL4Ra. For those who cannot have this treatment, we will use the genes and proteins to tell us which type of treatments that might improve their asthma. Therefore, this approach of Precision Medicine will bring newer more effective treatments to subgroups of severe asthma. We foresee that this research will tell us exactly who needs treatment with these antibody treatments, and this will allow patients to take better control of their asthma. This is a pioneering piece of research because this is the first time that this approach has been taken in the treatment of asthma or any other chronic disease. If we are successful in our objectives, this might pave the way for the establishment of Precision Medicine not only in severe asthma but also in other respiratory and non-respiratory condition, that will provide benefits to a large range of patients suffering from diseases such as severe asthma.

UKRI Gateway to Research · FY 2025 · 2025-03

The project aims to advance the adoption of engineered vascular tissues (EVTs) as a novel in vitro model, integrating this approach into the research conducted in Professor Sanjay Sinha's laboratory. Professor Sinha, a leading expert in the use of induced pluripotent stem cell (iPSC)-derived vascular smooth muscle cells (SMCs), and his team will utilise iPSC-derived SMCs with mutations predisposing patients to aortic aneurysmal disease in EVTs. The key objective is to assess the suitability of the EVT model for linking genetic mutations to mechanisms of aneurysm formation by combining iPSC-derived SMCs with a detailed proteomic analysis of the extracellular matrix (ECM) within these three-dimensional tissues. ECM remodelling is a hallmark of many vascular diseases, particularly aneurysm formation - a condition associated with ECM degradation and remodelling. iPSC-derived SMCs enable the study of defined pathogenic mutations, whereas primary SMCs are limited by their proliferative capacity and are prone to phenotypic changes and senescence in culture. The ECM profiles of EVTs created from iPSC-derived SMCs will be compared to those of human aneurysmal tissues. Unlike conventional two-dimensional cultures, EVTs retain the newly secreted SMC ECM, offering a more pathophysiologically relevant model. This collaboration between Professor Sinha’s and Professor Mayr’s laboratories will provide thorough characterisation and validation of the EVT model by incorporating iPSC-derived SMCs into EVTs and comparing their ECM profiles to actual human aneurysmal tissues. This approach offers a significant advancement by providing more accurate and relevant research outcomes in vascular disease studies. Ultimately, developing an accurate in vitro human 3D model of aortic aneurysm disease using EVTs will reduce the need for thousands of animal experiments each year and yield better scientific outcomes by enabling the dissection of human disease pathology and the screening and testing of new therapeutics.

UKRI Gateway to Research · FY 2025 · 2025-03

Stratospheric aerosol injection (SAI) has been the subject of increasing scrutiny as a potential climate measure, with most scientific attention focused on its efficacy in reducing net global warming. However, knowing that SAI would likely be effective does not answer the question of whether it is a “good idea” as a climate measure: whether the deployment of SAI would reduce the overall detrimental impacts of Earth heating relative to scenarios in which it is not deployed. Attempts to answer this question face two major obstacles. First, investigations of the physical response to SAI have mostly focused on its ability to reduce global mean temperatures; however for outcomes directly related to human impacts such as drought, air quality, or weather extremes, SAI is expected to produce different results than cooling through a reduction of greenhouse gases. Deeper engagement from Earth scientists is required to assess these impacts in relation to cooling from SAI versus GHG reduction. Second, producing ever more detailed scenarios of SAI deployment is not sufficient to produce effective risk analysis. It centralises SAI and its physical effects as the primary question driving future decisions, ignoring the social, political and economic dimensions. This can lead to studies which treat representative scenarios of SAI (or its absence) as comparable predictions of the future, rather than as indicative simulations which can help us to understand physical differences only. It also limits Earth scientists’ understanding of which physical risks are likely to be most – or least – consequential, and therefore which responses most urgently need more research. A research framework is needed which integrates risk analysis with Earth system modelling. This would allow risk analysts to more effectively explore the consequences of different climate measures while guiding researchers in Earth science towards the unanswered gaps in SAI modelling which most affect assessments of future risk. We therefore propose a new framework for physical modelling, designed to provide the information needed for cross-disciplinary risk analysis. Rather than continuing to build and refine scenarios, we instead choose to focus on a limited set of (mostly existing) scenarios, and to develop an understanding of the relationship between SAI and physical outcomes in ways which can inform risk analysis. We complement these scenarios with simplified sensitivity simulations to improve our understanding of the physical responses of critical systems to different climate measures (including SAI strategies, termination shock, SAI-based peak shaving, emergency SAI deployment, and different emissions mitigation levels). These responses are then translated into inputs for holistic risk assessment as a collaborative task with experts in risk analysis, based on the key factors which are expected to be relevant in future scenarios – centralizing the issue of how different risks are mitigated, exacerbated, or compounded by different climate measures, rather than starting from the question of SAI deployment. This project will set the standard for future assessments of all climate measures. By integrating risk analysis into our understanding of SAI, we ensure that the end results will be an improved understanding of the physical impacts of different climate measures which is guided by experts in risk analysis. This then enables those experts to provide holistic risk-risk analysis of different futures with and without SAI, and we anticipate our framework will continue to grow and provide policy-relevant information far beyond the end of this programme.