UNIVERSITY OF EDINBURGH

UKRI Gateway to Research · FY 2025 · 2025-07

The correct growth, morphogenesis and patterning of an organ or tissue during development is essential for its function in adulthood. The majority of organs (such as heart, lungs, intestine), develop during the embryonic period in order to be functional by birth, while others (e.g. lymphoid structures and the salivary glands) continue to mature into the neonatal period or into puberty (such as the mammary glands). The salivary glands (SG) develop through a process known as branching morphogenesis, where the glandular epithelium undergoes rounds of branching and clefting, to create a branched organ which is capable, by the time of weaning, of saliva production. A number of precisely timed signalling events are necessary for this correct growth and patterning, and the phenomenon involves multiple cells working together. Recent studies have implicated macrophages (Mf) as having a pivotal role in organ development, in addition to their classical phagocytic roles. Mouse mammary gland Mf are recruited to the epithelium and provide vital cues for branching morphogenesis during embryogenesis. Furthermore, Mf-deficient mice experience altered mammary gland branching and elongation during puberty and pregnancy, resulting in a lactational defect. Similarly, Mf are recruited to the developing pancreas and kidney, and their absence results in abnormal development. While we have recently explored the role of Mf in SG regeneration, and we have shown that Mf are necessary for efficient epithelial regeneration after injury in adulthood, it is not known whether Mf play a key role in SG development. In preliminary data we have shown, for the first time, that a mouse model which exhibits macrophage deficiency (the Csf1rFIRE/FIRE mouse) displays aberrant SG development. Thus, in this project we will ascertain how macrophages influence salivary gland development and branching morphogenesis. We will address this question via 3 aims: Aim 1: Characterise how SG development occurs in the absence of macrophages Aim 2: Interrogate the nature of macrophage-epithelial dialogue during SG development Aim 3: Explore whether exogenous replacement of macrophages or growth factors can mitigate against SG developmental delay While work continues to understand better the processes of SG epithelial development and the key signalling pathways involved, to date there has been no exploration of the involvement of immune cells, despite evidence showing that such interactions, particularly with relevance to macrophages, are important in the development of other organs. The findings of this project will provide a better understanding of the precise processes of SG branching morphogenesis and will ascertain the involvement of macrophages therein. Furthermore, the project will generate a number of datasets which will be widely available and will be of interest both to researchers working in the field of SGs and to those working in related fields, such as developmental biology and immunology.

UKRI Gateway to Research · FY 2025 · 2025-07

Environmental science underpins the knowledge and skills that our UK job market needs for the transition to a sustainable future. The green sector has been expanding rapidly, with global green job postings increasing by 8% annually over the past five years. This is particularly crucial for the UK economy, where demand for green talent is escalating; opportunities in the environmental sector increased by 46% between 2023 and 2024 and the hiring rate for ‘green talent’ is estimated to be 72% greater than the hiring rate for talent overall. Despite this buoyant picture, the environmental sector is facing two major issues. Firstly, the supply of job opportunities is outstripping demand - the availability of people to fill the growing number of green roles increased by only 5.3% - a fraction of the increase in opportunities. At the same time, the UK environmental sector is among the least diverse with racial, gender and disability inequality in representation. Identifying and eliminating barriers to building a diverse and cohesive workforce, fully equipped with the skills and understanding of the challenges and their solutions, is key to a socially just and economically viable future. We have identified three key stages where diversity in the environmental sciences appears to be stifled or lost: 1) school age pupils between the ages of 14 and 18, 2) students leaving tertiary education, and 3) retention within the jobs market at early to mid-career level. This is often attributable to decisions around the perceived lack of secure, or financially beneficial, career routes in the environmental sector. Given the demand and expanding opportunity that exists in the environmental job market, ensuring these routes are visibly open to all is key. Using a Theory of Change approach, AdaptABLE will co-develop a roadmap, with input from under-represented groups at multiple stages, to a range of pathways into jobs across the environmental sector.  As a starting point, we will draw from our partnership of over 30 university, governmental, non-governmental and industrial organisations and companies that work across the whole of NERC remit. We will explore the potential reach of different online and in-person mechanisms to showcase both the opportunities and the diversity of colleagues successfully pursuing careers in the environmental sector. We will work with pupils and early career researchers to design pathways to impact, and establish an evidence base of data and feedback on the engagement with identified activities. We will then evaluate the effectiveness of our activities across our broader partnership, inviting challenge from the groups we aim to support and the employers and educators that train and employ in the environmental sphere, to test the effectiveness of our outputs and establish where the focus of the next stages development beyond this project should lead. The green transition provides significant opportunities in the coming years across a range of sectors. Environmental science and a skilled and fully diverse workforce will be key to both the UK economy and socially just society of the future.  

UKRI Gateway to Research · FY 2025 · 2025-06

With currently 3 billion people lacking access to broadband internet worldwide, European operators are struggling to fill the white areas with insufficient or nonexistent connectivity. In light of the early promises of 6G wireless networks, it is tempting to consider non-terrestrial networks as complementary to the ground-based radio and fiber infrastructure. However, radio frequency-based satellite systems are nearing their capacity limits and cannot be scaled further. Free-space optical technology is a natural alternative to deliver greater capacity and to better address data security needs by leveraging quantum communications. The first optical intersatellite links are being deployed in commercial networks at relatively low data rate (10 Gbps). However, once the most important remaining research challenges are resolved, they could rapidly expand and serve as a catalyst for the development of a new communication backbone in the sky, consisting of aerial and space optical nodes at different altitudes. The overarching aim of the FOCAL project is to train a new generation of highly qualified doctoral candidates in developing innovative aerial and space optical wireless technologies that will provide future telecommunication networks with ubiquitous connectivity, resilience, and quantum-proof security. In addition to contributing to the fundamental understanding and technical know-how of such networks through co supervised individual research projects, FOCAL will train talented and innovative researchers with multidisciplinary expertise and skills that are desirable in this European industrial sector. This will be achieved through a combination of theoretical and hands on research training provided by a unique consortium of 16 academic and 10 industrial partners from 8 countries, resulting in collaborative research including co-supervision and secondments, as well as transferable training skills, which is necessary for prosperous careers in this prominent R&I area.

UKRI Gateway to Research · FY 2025 · 2025-06

This project aims to experiment with new ways to measure gender differences in everyday mobility using (geographic) digital footprint data, which is collected from people's interactions with mobile phones and other devices. While these data provide detailed information about people's movement, they only rarely have information on their gender. We will develop new methods for disaggregating these data based on gender and explore how travel patterns differ at an unprecedented level of spatio-temporal resolution. We will work with data sources available from the Urban Big Data Centre at the University of Glasgow, combining detailed movement data with evidence on the relationship between gender and transport. With a focus on active travel, we will look at what differences might be detected in the data based on gender. Our process will allow for a reproducible method to examine these gender differences from new forms of mobility data. Our project will use Scotland as a case study to develop our methods as there is a rich data landscape available with a wide range of digital footprint data on travel and transport. Additionally, we maintain a close connection with Sustrans, the UK leading charity aimed at favouring active travel, and the Scottish policy context, currently working towards just transitions for the transport sector. We will carry out our research through working with partners to gain input on how best to develop outputs that can inform policy (WP1). Gathering data on travel choices and other characteristics from existing surveys and research will inform a working model of gender differences in mobility (WP2). Using this knowledge, we will use digital footprint data to map and analyse mobility traces for different genders, applying a level of confidence measure to the patterns found (WP3). The project's findings will be used to inform transportation policies and sustainability transitions. By understanding how gender differences in mobility patterns impact transportation systems, policymakers can develop more inclusive and effective policies that promote sustainable mobility for all.

UKRI Gateway to Research · FY 2025 · 2025-06

With the advent of JWST and the launch of Roman in 2027, the next 5 years represent a step-change in our ability to characterize the atmospheres of known directly imaged exoplanets and to directly image lower-mass and cooler exoplanets. We propose a transformational program that will lead from the characterization of currently known directly imaged exoplanets and brown dwarfs to the first direct images of young Saturn mass and solar-system age giant planets. Characterizing the atmospheres of these planets is a key science goal and perfecting the technology and techniques to do so will be critical for the success of future space missions such as the Habitable Worlds Observatory, which will yield the first images of potentially habitable true Earth twins.  We propose 3 work packages using VLT, JWST, and Roman: 1) A 3-d view of brown dwarf and giant exoplanet atmospheres: Variability monitoring probes the 3-d time-resolved structure of exoplanet atmospheres. In Cycle 2, JWST will measure spectroscopic variability for 5 L/T transition brown dwarfs and young planetary mass objects (GO 2965, 3548, 3375, 3181, PIs Biller, Vos, Whiteford, Zhou). Coverage of spectral features inaccessible from the ground will lend direct insight into the structure of these atmospheres and the mechanism driving variability.  We will also extend variability monitoring to high-contrast companions using the novel VLT/ERIS vAPP coronagraph (2 nights of monitoring acquired in October 2023, PI Sutlieff). 2) Completing the census of young Jupiters: we are conducting a VLT/ERIS + SPHERE survey for young giant planets in overlooked nearby young associations to improve the census of giant planets at the youngest ages (<10 Myr) and determine how companion fraction varies as a function of association age. 3) The First Direct Images of young sub-Jupiter planets and Solar System Age Giant Planets: Several JWST/NIRCam surveys are underway to image down to Saturn mass companions for nearby young stars (GO 4050, PI Carter, co-I Biller, Survey 6005, PI Biller, GO 5835, PI Carter, co-I Biller).  Our team is playing a leading role in these surveys.  In 2026, Gaia DR4 will provide a treasure trove of ~10000 astrometrically detected planets. Roman may image the brightest of these planets, yielding the first direct images of solar system age giant planets. PI Biller is an ESA-appointed representative to the Roman Coronagraph Community Participation Program. Combining JWST, Gaia, and Roman results will enable the most in-depth study of giant exoplanet demographics to date.

UKRI Gateway to Research · FY 2025 · 2025-06

Performative Blackness and Black Histories in Scotland, 1839-1939, initiates a new cultural history of Scotland: one that reconnects Scotland with its imperial and colonial past, and reveals the hidden history of representations of blackness embedded in Scottish popular culture at a time of rapid colonial expansion and social upheaval. This study, the first of its kind, will explore performative blackness, that is, racial impersonation of people of African descent through the use of prosthetics, movement and speech, across a range of interrelated performance genres in Scotland. Performative blackness was abundant in Scottish popular culture in the nineteenth and early twentieth centuries, but has been subject to silence and erasure. This project will examine how blackness was performed by white and black entertainers in Scotland in the nineteenth and early twentieth centuries. Its primary focus will be musical theatre, including music hall, variety theatre and early jazz, exploring both professional performance and the local amateur responses it inspired and how these changed over time. Furthermore, it will make connections between performative blackness witnessed in musical theatre and parallel genres of entertainment including the circus and human exhibitions. This project contributes to Scottish History and Black British History, and puts them in conversation with each other. It adds to a new global history of Scotland which in recent decades has begun to address enduring silences on the legacies of enslavement, colonialism and imperialism, revealing Scottish universities as engines of racial thought, and Scotland's economy as disproportionately involved in enslavement in the Caribbean (Mullen & Gibbs, 2023: 927). This project considers legacies of empire in Scottish cultural life by examining widespread representations of blackness in Scottish popular culture and the audiences who consumed and reproduced them. It pays much needed attention to the lives and labours of black diasporic peoples living and working in Scotland in the nineteenth and early twentieth centuries, including black performers. In short, it restores a history of race-making in Scottish culture to the historical record, and initiates a public conversation about the legacies of this history.

UKRI Gateway to Research · FY 2025 · 2025-06

We address the major global health challenge posed by Taenia solium cysticercosis in highly endemic areas. This zoonotic tapeworm infection is a neglected tropical disease (NTD) with substantial health and economic impacts in regions where pork consumption is high, and pig farming is practised extensively in areas with low sanitation and stark poverty. Northern Uganda is one such area, but this parasite is endemic or suspected endemic in at least 65 countries across central & South America, sub-Saharan Africa and Asia making T. solium a parasite of truly global concern. Context and Global Health Challenge: Uganda and other endemic countries face a substantial burden from neurocysticercosis (NCC), a severe neurological condition in humans resulting from T. solium infections. The parasite's life cycle involves pigs as intermediate hosts and humans as definitive hosts. NCC arises when humans are infected through faecal-oral contamination with infectious eggs resulting in NCC as an aberrant intermediate infection. The disease's global impact is profound, with an estimated annual burden of 1.2million Disability Adjusted Life Years (DALYs).  Of the NTDs considered by the Global Burden of Disease study 2021, cysticercosis has the third highest burden after malaria and schistosomiasis. In addition to its health impact, T. solium has an economic burden, resulting in a reduction in the value of infected pigs. In Uganda, where widespread free-roaming pigs and low sanitation levels increase the risk of T. solium transmission, the economic burden is estimated as at least $75million/yr. Project Goals and Objectives: Our primary goal is to evaluate the incremental effectiveness of a joint human-porcine mass anthelmintic administration strategy compared to human only treatment, for the control of T. solium in Northern Uganda. We will determine the difference in effect through a cluster randomised controlled trial where the primary outcome is prevalence of porcine cysticercosis (PCC) (infection of pigs with the intermediate stage of the tapeworm), and secondary outcome is human cysticercosis (HCC) prevalence. Transmission simulations will inform projection of future impact on transmission and burden of disease estimates over a 10yr time frame, feeding into an economic evaluation of cost-effectiveness from the health system perspective and cost-benefit analysis from a societal perspective. Finally, we will determine the feasibility and acceptability of such joint One Health interventions from the perspective of policy makers in the health and agriculture sectors. Potential Applications and Benefits: This proposal seeks to demonstrate how interventions implemented across non-human and human hosts can improve public health, emphasising the importance of interdisciplinary, collaborative working. It represents an important step in addressing a neglected health problem in Uganda through reducing the burden of T. solium infections. Our intervention, supported by modelling, will benefit the community at large and enhance the livelihoods of smallholder pig farmers whilst providing valuable insights and frameworks that could be applied to similar health challenges worldwide. The proposal provides opportunities to influence resource allocation and policymaking, focusing on sustainable and locally acceptable control strategies. This proposal represents an example of the One Health concept in practice and is reflected in the multi-disciplinary background of the research team which represents a wide range of relevant expertise in the epidemiology and control of NTDs in Low- and Middle-Income Countries (LMIC) contexts.

UKRI Gateway to Research · FY 2025 · 2025-06

Pestiviruses are a global economic burden for livestock production, although exact figures are often difficult to ascertain. Whilst Classical Swine Fever virus (CSFV) has been eradicated in the UK, both Bovine Viral Diarrhoea virus (BVDV) and Border Disease virus (BDV) continue to cause significant economic impact. It is estimated that BVDV costs the UK cattle sector around £36.6M annually (APHA). While the financial impact of BDV on sheep is difficult to quantify, around 30% of UK sheep flocks have incidence of BD with an estimated 2-8% reduction of lamb production in affected flocks (FAS). CSFV remains a disease of global impact and is notifiable to the world organisation of animal health. Reintroduction of the virus to the UK could be devastating; the eradication of a widespread outbreak in the Netherlands in 1997/98 reportedly cost of $2.3 billion1. Most pestiviruses are named based on the host species from which they were first isolated, but these closely related viruses can display interspecies transmission. In the UK it has been reported that as many as 20% of cases identified as BD are actually caused by BVDV infections2, suggesting that cross-species transmission could impede control strategies. While there are effective vaccines available for CSFV and BVDV, there is currently no vaccine against BDV. Vaccines are not cross-protective. Pestiviruses are a genus within the Flaviviridae family of positive-sense, enveloped RNA viruses that can be directly transmitted or vector-borne. Host tropism within the family is broad and many of the pathogens can cause severe illness. It was previously shown that the vertebrate host chaperone protein DNAJC14 is required for replication of the flavivirus Yellow Fever virus (YFV) in vitro3,4. It was also shown that knockout of the DNAJC14 gene in pig and cattle cell lines renders them non-permissive to replication of both CSFV and BVDV5. However, data generated in cellular systems does not always translate to the context of a whole organism6. Our previous work has shown that genome editing can be a viable tool to introduce genetic resistance to disease7,8. Within this project, we aim to generate ruminants with edited DNAJC14, which we hypothesise will be non-permissive to pestivirus (and potentially flavivirus) replication. In parallel, we aim to interrogate virus evolution in vitro prior to validating resistance in vivo. Taking into account the generation interval and financial cost of working with either cattle or sheep, the number of available viral isolates for testing in either species, together with the UKRI funding cycle, we propose to generate a cohort of sheep with edited DNAJC14 to test our hypothesis. The objectives are: To generate genome edited founder (F0) and F1 sheep with ablated DNAJC14 function To assess resistance to and evolution of BDV, BVDV, CSFV and selected flaviviruses in DNAJC14 edited primary cells and cell lines To determine in vivo efficacy of the DNAJC14 edit in the context of BDV challenge of F1 sheep Findings from this project have the potential to provide a genetic control option for pestiviruses and flaviviruses either through genome editing or genetic selection. It may also provide the basis to develop other antiviral strategies, such as small molecule compounds. This project contributes to the BBSRC priority of “Bioscience for sustainable agriculture and food”.

UKRI Gateway to Research · FY 2025 · 2025-06

This SE aims at addressing a number of challenging mathematical problems related to stochastic interacting systems, with particular emphasis on the regularity properties of the solutions, their limiting behaviour and numerical computation. The equations we analyse arise from the modelisation of real-world phenomena in several fields of application, including spiking neural systems, hydrodynamics and financial/energy markets, and share nonlinearity as a common underlying trait. Critically, nonlinearity intertwines with other relevant features that include: low regularity of the coefficients, noise degeneracy, jump-diffusion dynamics, and high- dimensionality. The study of stochastic interacting systems is highly multidisciplinary from a two-fold perspective. On one hand, they have become a widespread modelling tool in a variety of applications. For example, they are used to model human neuron interfaces, particle systems, but also interacting agents in economics and finance, in relation to managing risk and decentralised production of renewable energy. On the other hand, the set of mathematical and computational tools needed to reach a holistic understanding of stochastic systems is very vast: ranging from stochastic (partial) differential equations, random measures, rough paths, gradient flows in metric measure spaces, numerical probability and computer simulation. We provide a team of experts that analyse stochastic systems integrating several approaches and techniques. The complementary expertise across the network, together with the consolidated experience and excellence of the key participants in their research areas, places our network in the privileged position to make relevant contributions across interconnected research fields, and to contribute to the training of the early career researchers involved in the project in an exciting field of pure and applied mathematics, with the possibility of boosting their careers in both academic and non-academic sectors

UKRI Gateway to Research · FY 2025 · 2025-06

The European Extremely Large Telescope (E-ELT) is set to transform many areas of astrophysics when it is commissioned in the early 2030's.  The first suite of instruments that will harness the huge collecting area and resolving power of this 39-m diameter telescope includes HARMONI -- the UK-led near-infrared integral field spectrograph which will simultaneously create high-resolution images and spectra of planets, stars, and galaxies.  This instrument, aided by the exquisite angular resolution delivered by the E-ELT through its adaptive optics system MORFEO, will carry out a large number of breakthrough science programs, including monitoring the weather on planets and moons in the solar system, measuring the atmospheres of (exo)planets around nearby stars, studying the dynamics of stars around nearby massive black holes, determining the structures and dynamics of distant galaxies, and establishing the physical and chemical properties of the first galaxies that formed in the Universe. The Principal Investigator (PI) for HARMONI is the principal advocate for the HARMONI instrument and provides the overall strategic direction and leadership of the Project. The PI is charged with enabling the project’s overall success by ensuring that the necessary level of commitment from the consortium members and funding agencies is met, and that the science capabilities of the instrument are well advertised/promoted,  and exploited to the full. The PI is responsible for the high-level management of the project and for maintaining broad oversight of the project and its progress, but is not responsible for its day-to-day technical and project management. The PI is the primary contact point with the European Southern Observatory (ESO) as described in the ESO contract.

UKRI Gateway to Research · FY 2025 · 2025-06

All our cells contain the same DNA and the same genes. However, not all genes are needed in every cell type. Cells can turn off genes that are not needed in several ways. One of these is by chemically modifying DNA by methylating it.   When people develop cancer, the patterns of DNA methylation change. Scientists believe these changes could play a crucial role in the helping tumours grow. There's a lot of interest in finding ways to manipulate these DNA methylation changes as a cancer treatment or to use them to help diagnose cancer. However, we are not sure how why these DNA methylation changes happen in cancer.  This makes it hard to understand how important they are and to use them to help treat patients.   One of the most common changes in DNA methylation in cancer is its loss from parts of the genome where genes are absent or inactive which scientists call heterochromatin.   We have found that a gene known as DNMT3B is important in placing DNA methylation on the heterochromatic part of the genome. We think this observation could be a key that helps unlock our understanding of why cancers might lose methylation from heterochromatin and how that promotes cancer.   In this project, we will investigate this further in the laboratory by studying colorectal cancer, a type of cancer where DNMT3B seems to play an important role in causing the disease. Specifically, we want to know: • What goes wrong in cells when the heterochromatic part of the genome losses DNA methylation. • How DNA methylation gets placed at on the heterochromatic part of the genome. • How the heterochromatic part of the genome changes during the development of cancer.   Our study will help us understand how changes in DNA methylation contribute to colorectal cancer, which causes around 10% of cancer deaths in the UK. We will help understand whether it might be possible to treat colorectal cancer by targeting DNMT3B in the future. Since similar losses of DNA methylation are seen in other cancers, our findings could have broader applications for cancer research and treatment. Furthermore, some people are born with a rare genetic syndrome known as Immunodeficiency Centromeric Instability and Facial Anomalies Syndrome Type 1. This is caused by mutations in DNMT3B, and the cells of these people have little DNA methylation in the heterochromatic part of the genome. It is possible our results could help us understand why DNMT3B mutations cause this syndrome.  

UKRI Gateway to Research · FY 2025 · 2025-05

In the UK, 7.6 million people are living with heart and circulatory diseases which are subsequently responsible for 27% of deaths, with myocardial Infarction (MI) and heart failure a major factor (BHF Factsheet 2024). Rodent MI models using infarcts generated via invasive thoracotomy have been the cornerstone of cardiovascular research, allowing investigation of the pathological mechanisms driving adverse outcomes, identifying imaging/therapeutic targets and evaluating novel therapies. Rats are particularly important to preclinical molecular imaging studies using positron emission tomography (PET), owing to their larger size vs. mice and the resolution of preclinical PET scanners (~1mm). In the last decade across the UK, 79 papers have been published using invasive rat MI models, representing the use of thousands of rats. This application aims to significantly reduce these numbers, and greatly refine these models which are classified as severe, through the development of a first-of-its-kind ultrasound guided minimally-invasive approach to MI generation in rats. This novel model, developed by embedding the 3Rs principals of reduction and refinement, will replace the gold standard approach of invasive infarct generation in rats and remove the need for: mechanical ventilation, skin incision, thoracotomy, lung collapse, pericardium rupture, exteriorisation of the heart, muscle/skin wound closure and breathing reflex recovery. Due to the exclusion of these aspects, we anticipate that our minimally-invasive model will result in a significantly higher recovery rate which will reduce the number of animals required, as well as reducing pain and suffering while shortening procedure and recovery times. Further to this, under ultrasound guidance, we propose that there will be greater control of infarct size, reducing the likelihood of unnecessarily large infarct sizes and missed occlusions. These expectations are based on an equivalent minimally-invasive model in mice using permanent occlusion to generate MI which has recently been developed and is now in use in our research centre(1,2). This published mouse model provides the blueprint for our first-of-its-kind rat model and establishes the proof-of-concept that this can be achieved in rodents, increasing our likelihood of success. The aims of this project are to 1)develop a rat ultrasound phantom to be used for equipment optimisation and future training purposes, 2)establish the recovery, accuracy and actual severity of this proposed minimally-invasive rat approach using permanent coronary artery occlusion and 3)for the first time in any rodent species establish a minimally-invasive method of temporary coronary artery occlusion to induce reperfusion injury-driven MI in rats.

UKRI Gateway to Research · FY 2025 · 2025-05

Antimicrobial resistance (AMR) is an increasing global threat to both human and animal health as infections become increasingly difficult to treat with commonly used antimicrobials. Vaccination is a powerful approach for limiting the impacts of AMR by disease prevention. However, major bacterial pathogens such as Staphylococcus aureus remain refractory to vaccine development due, at least in part, to a lack of translation of vaccine testing in animal models to human protective efficacy. Clinically, S. aureus is a major infectious burden of humans and farmed animals with particular lineages specialized for causing mastitis in ruminants. This bacterial infection of the udder generates a £120 million economic cost to UK sheep farmers annually as well as being a food security concern with 6% of ewes culled annually. In order to achieve the United Nation’s Sustainable Development Goal (SDG) of Ending Hunger, food production efficiency needs to be increased with reductions in underperforming animals. The ability to vaccinate ruminants to eliminate productivity costs associated with mastitis would be hugely beneficial in our fight to create a sustainable future and to limit the impacts of bacterial AMR. To create an effective S. aureus vaccine targeting mastitis we first need to understand what bacterial factors to target and how to promote an effective immune response. A major pathology during chronic sheep mastitis is the development of abscesses that promote persistence. These abscesses are palpable in the udder as lumps and will often inform the farmer about whether to cull a ewe. In humans, such abscesses contain a dense population of viable bacteria at the core called Staphylococcal abscess communities (SACs) that are protected from the immune system and antibiotic treatment by an outer fibrin layer, promoting bacterial persistence and infection recurrence. There is currently a lack of understanding of the bacterial factors required by sheep strains of S. aureus to produce these SACs during chronic mastitis limiting the design of a vaccine targeting sheep mastitis that would prevent abscess formation. This project aims to address this challenge by (i) identifying potential vaccine candidates for S. aureus-mediated sheep mastitis, and (ii) identifying the key immune cell interactions for effective control of ovine S. aureus strains in vitro. These aims will be achieved through the following objectives: Use transposon mutagenesis to identify the bacterial factors required for SAC formation in vitro by ovine aureus strains Evaluate bacterial factors required for SAC formation as vaccine candidates Establish in vitro systems for evaluating the interaction of aureus with ovine immune cells isolated from milk and blood Use transcriptomics to identify markers of aureus control by immune cells isolated from sheep Taken together these aims and objectives will identify potential vaccine candidates involved in abscess formation that could be employed to control sheep mastitis. Additionally, it will identify markers and pathways associated with effective S. aureus control in vitro, which will aid in vaccine design by informing routes of vaccine delivery and enhancing vaccine success. By addressing major gaps in our understanding of the pathogenesis of sheep mastitis, this project has the long-term vision of enhancing ewe welfare, increasing financial return for farmers and contributing to the SDG of Ending Hunger through increased food security globally.

UKRI Gateway to Research · FY 2025 · 2025-05

The first objective of the National Quantum Strategy (NQS) missions, published on 14th December 2023, is to enable the development of “UK-based quantum computers capable of running 1 trillion operations and supporting applications that provide benefits well in excess of classical supercomputers” [1]. At present, quantum computers are far from this objective: qubits are noisy, and approximately 1% of operations fail [2,3]. To fulfil the NQS missions, quantum computers need to be made fault-tolerant using quantum error correction (QEC). The essential principle underpinning QEC is that multiple noisy qubits can be combined to form so-called logical qubits. These logical qubits are robust against errors and will serve as the fundamental building block of arbitrarily scalable quantum computers. During this fellowship, my primary aim is to develop the tools and innovation required to integrate QEC into near-term quantum computing architectures. The National Quantum Computing Centre (NQCC) recently invested £30m in seven quantum computing testbed systems across a range of qubit technologies [4]. I will collaborate with the NQCC to design and deploy QEC protocols for each of the testbed devices. This will be the most extensive comparative assessment of fault tolerance in quantum computers to date. The experimental data gathered will be pivotal in guiding the NQCC in strategic decisions on which qubit technologies to support in the long term. Quantum computers must be built in tandem with classical co-processors to decode QEC measurement information before the qubits become irreversibly corrupted. For a full-scale quantum computer, QEC measurement information can be generated at rates of terabytes per second [5]. As such, access to high-performance decoders is critical. To alleviate the load on classical co-processors, I will develop low-power parallel decoding algorithms. Through a collaboration with the Edinburgh Parallel Computing Centre, I aim to implement these algorithms on specialised hardware such as GPUs, FPGAs, and RISC-V boards. To accelerate the transition to fault-tolerant quantum computing, it will be necessary to discover methods for reducing the overhead of QEC.  I will conduct research into quantum low-density parity check (QLDPC) codes as a resource-efficient alternative to surface code QEC. To this end, I will leverage existing expertise from classical communications technology to design QLDPC protocols for near-term quantum hardware.  Further to this, I will develop improved methods for performing QLDPC encoded computation and conduct resource estimations for practical quantum algorithms. These new QEC protocols, as well as their benchmarks, will be made publicly available through an online database. Given the steep learning curve for newcomers to QEC, there is a pressing need for intuitive software that simplifies the exploration and evaluation of fault-tolerant protocols. To address this, I will develop user-friendly design automation tools to streamline the incorporation of QEC into the quantum computing stack. In the first instance, I will develop an end-to-end QEC compiler that automatically translates a high-level description of a quantum algorithm to a fault-tolerant circuit. This will simplify the process of fault-tolerant design and accelerate the rate at which new QEC protocols are deployed in hardware.

UKRI Gateway to Research · FY 2025 · 2025-05

Identifying the role of host genetics associated with disease resistance in humans and animals has led to important advances in disease control, but there is increasing evidence that individuals not only vary in their resistance to acquire infectious pathogens, but also in infectiousness - their ability to transmit pathogens. The contribution of host genetics to the phenotypic variation in infectiousness is largely unknown for most infectious diseases. An urgent - but elusive - agenda in disease ecology and epidemiology is therefore to identify the genetic drivers of variation in host infectiousness. This proposal will focus on the genetic and immune determinants and evolutionary constraints underlying individual variation in host infectiousness. We will harness the fruit fly Drosophila melanogaster as an established model system of infection, immunity, and behaviour to disentangle the genetic and immune determinants, and evolutionary constraints underlying extreme host heterogeneity in pathogen transmission.  We will further enhance these empirical strengths by employing recently developed statistical inference and epidemiological modelling tools which allow quantifying the effect of known host genetic polymorphisms on specific epidemic outcomes. Given the pervasive threat of emerging infectious diseases in human, animal and plant populations, our aims are to produce timely and novel research focusing on the genetic and immune determinants and evolutionary constraints underlying individual variation in host infectiousness: While we know much about genetic variation for some disease-related traits, the contribution of host genetics to infectiousness is generally unknown. A deeper understanding of the relationship between host susceptibility and infectiousness, and their relative contributions in transmission dynamics, is urgently needed to devise and predict the outcome of disease control strategies. Immune-related pathways are well-described in several vertebrate and invertebrate systems, but we have little knowledge of the extent to which immune pathways regulate variation in host infectiousness. Genetic variation is the fuel for evolution, but how host infectiousness is likely to evolve in response to disease control methods is unknown. We propose selection experiments as a powerful approach to uncover evolutionary constraints and trade-offs between host infectiousness and other traits. Our overarching, long-term goal is to achieve both an advance in our fundamental understanding of the role of host heterogeneity in infectious disease, and useful insight into biomarkers for disease control and prevention in animal and human populations. These aims align directly with UKRI’s Strategic Delivery Plan, specifically with the aims of supporting world-class ideas in bioscience discoveries by understanding the rules of life and in achieving world-class impacts, particularly in the integrated understanding of health.

UKRI Gateway to Research · FY 2025 · 2025-05

It has been known for more than a century that the Sun rotates "differentially": its equator rotates more rapidly than regions near the pole, and parts of its interior spin at different rates, too. This differential rotation is thought to play a major role in building the Sun's organised magnetic fields, which ultimately drive Solar activity that can impact our technological society. But we still don't have a good theoretical understanding of how this differential rotation arises. For the past several decades, most models have suggested it comes ultimately from the action of convection -- the roiling motions of plasma that occur in the outer third of the Sun. These transport heat, in much the same way as a boiling pot of water on a hob, and they can also transport angular momentum. But recent observational and theoretical developments have called this view partly into question: for example, observations indicate that the convective motions are weaker than expected (so they might have a tough time generating the observed rotation profiles); meanwhile the latest supercomputer simulations have suggested that small-scale magnetic fields in the Sun are much stronger than previously believed, so that their transport might "win out" over the convection. Here, we propose to use a series of carefully-constructed numerical simulations to determine whether the Sun's observed equatorial acceleration is driven primarily by the convection or (directly or indirectly) by the magnetism. It isn't possible to simulate all aspects of the problem at the same time, even on the largest supercomputers available today: the range of scales (of motion and magnetic field) present in the Sun is simply too large. In particular, we can't self-consistently capture the generation of the magnetic fields and their feedback on the flow in the limit of "small magnetic Prandtl number" -- the limit that applies in the Sun. But one of the key ideas in our work is that it is possible to model the angular momentum transport specifically -- which gives rise to the differential rotation -- by solving a slightly simpler problem, called "magnetoconvection," in which magnetic fields of varying strength are essentially imposed amidst a simulation of turbulent convection. This method doesn't tell you how strong the magnetic fields actually get, but it can tell you what fields of a particular strength will do, and how they will affect the convection. We will use a combination of local simulations, which model a small portion of the Sun and can be run in extreme parameter regimes, alongside global spherical-shell models, to determine how the combination of convection and magnetic fields gives rise to the Sun's differential rotation. In parallel, we will use our simulations to determine how the properties of "inertial waves" amidst the convection -- which have recently been observed at the Solar surface -- depend on the flows and imposed magnetic fields, providing a new window into dynamics in the deep Solar interior.

UKRI Gateway to Research · FY 2025 · 2025-05

The Earth’s daily rotation dictates the timing of activities for almost all organisms and is assumed to explain the evolution of circadian clocks and daily rhythms. However, the evolutionary ecology of rhythms is poorly understood, especially for parasites/pathogens, for whom the environments experienced inside hosts and vectors changes dramatically over 24 hours. Yet, rhythms play fundamental roles during infections; for example, the time-of-day an infection is acquired by organisms as diverse as insects and mammals can determine whether they survive or succumb. Daily rhythms exhibited by hosts/vectors also affect the fitness of the parasites/pathogens they transmit. This includes the costs of time-of-day dependent dangers imposed by immune rhythms, and the benefits of time-of-day specific opportunities, such as the influx of nutrients available to parasites/pathogens following the rhythmic foraging of the host/vector. Yet, how parasites/pathogens cope with the constraints of environmental rhythms and exploit rhythmic opportunities, is a fundamental knowledge gap in understanding the evolutionary ecology of infections. Addressing this neglected aspect of infections is critical for vector-borne diseases because the activities of insect vectors – which are highly sensitive to rhythms in the abiotic environment – dictate the time-of-day that parasites/pathogens transmit and complete their lifecycles. Thus, we will push the frontiers by using the model system of Anopheline mosquitoes and malaria (Plasmodium) parasites to uncover how daily rhythmicity in transmission opportunities affects vectorial capacity, infection spread, and parasite evolution. Specifically, we will use field and lab experiments coupled with theoretical modelling to test hypotheses derived from integrating concepts of life history evolution with chronobiology and parasitology. First, we will quantify variation in the time-of-day that wild Anopheline mosquito vectors forage for blood (bite), uncover the environmental and physiological factors that generate variation between mosquitoes in biting time-of-day, and experimentally determine the consequences of different blood feeding times for survival, biting rate, and fecundity. Knowing how many, and what kinds of, vectors bite at different times of day will uncover the roles of rhythms in vectorial capacity. Second, we will test how biting time-of-day affects Plasmodium infection rate and proliferation within mosquitoes, and transmission to subsequent hosts. We will integrate these rhythms into the well-established theoretical framework for predicting malaria parasite fitness (R0) to estimate time-of-day-dependent transmission rates, identify which rhythms are the most influential for transmission, and predict the epidemiological consequences of shifts in biting rhythms. Uncovering which rhythms matter, and explaining why, for malaria transmission is urgently needed because malaria-transmitting mosquitoes are shifting when they bite. Third, we will reveal how parasites adapt in response to shifts in biting time-of-day. We will do this by experimentally evolving parasites through sequential cycles of host-vector-host transmission at the classical time-of-day (in the middle of the night) or at early, late, and erratic times of day for transmission, and comparing the resulting phenotypes (traits underpinning within- and between-host fitness) across treatments. Parasites express their own rhythms which exhibit genetic and environmental variation and so, identifying their evolutionary potential is central to predicting the short- and long-term consequences of the anthropogenic forces disrupting vector rhythms. By opening up a neglected aspect of the evolutionary ecology of infections, we bring a novel perspective to the NERC’s Environmental and Social Ecology of Human Infectious Diseases initiative, and will inform how to protect health, disrupt transmission, and identify intervention targets for a major disease.

UKRI Gateway to Research · FY 2025 · 2025-04

Volcanogenic massive sulfide (VMS) deposits are globally significant resources of copper, zinc, lead, silver and gold in the Earth’s crust, that have been targeted by miners for over a thousand years. These deposits have formed on the ocean floor since ~3.5 billion years ago and are preserved on land during mountain building processes associated with episodes of ocean closure. Given the growing urgency for countries to divest from fossil fuels and embrace a variety of renewable energy technologies, VMS deposits are now being targeted as potential sources for a variety of critical minerals. These include cobalt, tellurium, gallium and germanium, and are essential components in the manufacture of several technologies for the green energy transition. If present in significant quantities and economically viable, critical minerals can be extracted from some VMS deposits as by-products of base metal mining. The Caledonian-Appalachian orogenic belt extends from Norway, through Scotland, Ireland and Newfoundland, to maritime Canada and the northeast USA. It resulted from the progressive closure of the Iapetus Ocean from the Late Cambrian to Devonian, and along its length it hosts numerous VMS deposits. In the Canadian Appalachians, these include some of the world’s largest deposits, and those with the highest percentage metal from anywhere on Earth. Despite its comparable geology, in the British and Irish Caledonides only a handful of VMS deposits have been discovered and two deposits mined (at Avoca and Parys Mountain). This disparity in regional metal endowment is striking and unexplained. Furthermore, fundamental processes controlling critical mineral enrichment in these systems are poorly understood. This project aims to constrain the tectonic, magmatic and hydrothermal processes across the Caledonian-Appalachian orogenic belt to understand why some regions of the orogen are VMS-rich, and others poorly mineralized or devoid of any deposits, and what controls critical mineral endowment at the deposit scale. We will track magmatic and fluid processes through the chemical and isotopic analysis of rocks and their accessory minerals, trapped pockets of preserved melts and fluids, and the chemistry of host sulfide minerals. Detailed deposit-scale studies will include world class deposits (e.g. Buchans), subeconomic systems, host rocks barren of mineralization, and critical mineral-enriched systems. Our two-year research project will undertake detailed deposit-scale studies of VMS mineralization across the UK, Ireland and Newfoundland, and will be led by staff at the University of Edinburgh, University College London and the British Geological Survey. We will partner with leading Canadian Researchers to develop new models for magmatic-hydrothermal controls on metal budgets in VMS systems. Our results will potentially inform UK, Irish and Canadian policy on the critical mineral potential of these regions; enhance exploration globally through improved evidence-based targeting methods - possibly reducing waste; and facilitate more efficient mining through a greater understanding of the distribution of critical minerals within VMS deposits.

UKRI Gateway to Research · FY 2025 · 2025-04

Context: Silicon photovoltaic cells are by far the most common with >400GW of capacity installed in 2023. But they suffer from an Achilles' heel; they are bound by the laws of physics never to attain an efficiency greater than 31% as silicon’s bandwidth means they only generate electricity across a narrow range of wavelengths. Our technology utilises programmed assembly of biomolecules to template the synthesis of non-linear meta-atoms which interact with the sun's light and shift infrared wavelengths into the red region of the spectrum, so they contribute to electricity generation. This boosts the PV efficiency to a theoretical maximum >38%. Importantly, our technology can be sustainably produced using biomanufacture and is readily integrated into PV manufacture, but also easily retrofitted to existing PVs in the field. By boosting both installed and future capacity, the significant carbon savings will make a meaningful contribution to humankind's journey to meet the UN's SDG7 renewable energy goals, and ultimately net-zero. We have demonstrated design and fabrication of optical metamaterials in the lab (millilitre scale). Funded by Dstl/DASA we have achieved proof-of-concept for biomolecule-templated synthesis of nanoscale metallic resonators that interact with optical wavelengths of light. Our recent BBSRC Breakthrough Award took the first step towards upscale using engineering biology approaches to manufacture our template biomolecules in a bacterial chassis (sub-litre scale). These pilot studies give us great confidence in the technology with techno-economic analysis indicating we can deliver an attractive reduction in levelized cost of energy. Challenge addressed: Our metamaterial may be thought of as an optically-active additive that must now be encapsulated in a “binder”, akin to a pigment in a paint. The requirements for the binder are that it facilitates the transportation of the metamaterial to the PV’s surface, it acts to promote favourable orientation of the resonators and it forms a protective overlayer. These requirements must be delivered without compromising light transmission. The challenge that this bid tackles is the formulation of the binder material system to achieve a family of metaVarnish products to take our metamaterial from the lab to real-world deployment. Collaboration enabled: The award enables a new collaboration between the academic team and the National Formulation Centre at CPI. Elfick & Seviour have backgrounds in Engineering Biology and Electromagnetic Materials respectively, but lack the requisite expertise in coatings and formulations. The fit to NFC’s competences is excellent. We anticipate that this will be a long-term relationship as we re-imagine our metamaterial for different applications and reformulate our coating accordingly, e.g., metaInks for inkjet printing in optoelectronic devices. Aims and objectives: The aim of this Working with Centres Award is to accelerate us from TRL2 to TRL5 through delivery of a multidisciplinary collaboration delivering a PV coating technology. Facilitating rapid, large-area treatment, the material system must meet the challenges identified above with the end-goal of passing accelerated environmental tests prior to deployment in a field trial at the University of Edinburgh's 3MW solar farm. Potential applications and benefits: Whilst framed around silicon-based PVs, our technology can be redesigned to boost performance in any PV technology by harvesting wasted wavelengths of light. The benefits to solar energy sector stand to be considerable as will the contribution to addressing the drivers of climate change. Beyond this, the metamaterial coating has trickle-down applications across myriad domains including optoelectronics and architectural/horticultural/vehicular glasses.

UKRI Gateway to Research · FY 2025 · 2025-04

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 · 2025-04

The TERC Report highlights a set of key priorities crucial to our future. Of those, we are focusing on  socially and environmentally responsible approaches to engineering, nature-based engineering, and global engineering solutions. Environmental sustainability and the creation of a global community that is prepared to mitigate and adapt to climate change are common threads to those priorities, and arguably, some of the most important challenges that we will ever face. Engineering is at the interface between society and the environment, making it a powerful tool to fight climate change at a global scale. Women are disproportionately affected by the impact of climate change, and that their full inclusion in developing engineering approaches is crucial to finding effective solutions to these grand challenges. In order to understand the issues and potential that engineering brings to tackle this problem, we propose here the use of “failure modes”, a method taken from traditional systems engineering, to develop a network that delves into the complex relationship between engineering, nature, and society. Failure modes are commonly used in engineering as a methodical approach to identify and prioritize potential issues in design, manufacturing processes, or products. By examining the causes and effects of these failure modes, engineers can enhance reliability and improve outcomes. Drawing on this concept, our network aims to tackle the failure modes of current engineering practices, particularly in relation to climate change and its impact on women, children,  and underrepresented groups globally. Moreover, we want to empower them as crucial agents for the future engineering that we need. This systems-thinking approach will enable us to propose solutions for the future challenges of engineering. The failure modes will form the foundation of our proposal and guide our activities. Our failure mode analysis identified several areas that are critical to enable the future engineering that our planet needs, such as the inclusion of female talent, social acceptability, global data provision, involving underrepresented groups, interdisciplinarity, and working with limited resources. The excellence of our proposal stems from our unique perspective on engineering challenges and our approach to identify and address them . Following this whole systems approach, we have co-created our network with multiple partners: our core leadership team is composed of academics from a range of academic schools at the University of Edinburgh, University of Glasgow and Heriot-Watt University, and we have the support of several other colleagues in different academic, industrial and third sector institutions globally. Together, we are proposing a wide range of activities to grow and support our global network, including workshops, seed funding calls, training and dissemination activities, awards, a mentoring scheme, a coaching and leadership programme, secondments, building communities of practice, or design challenges that bring engineers from the Global South and the Global North together, among others. A relevant proportion of these activities will take the form of flexible funding calls to allow the inclusion of innovative and timely ideas. Our activities have a special focus on the role of education as a tool to empower children as future environmentally conscious engineers, and to create a society that reflects holistically on needs and resources. Moreover, we propose the use of feminist methodologies as a framework to nurture the diversity of our engineering profession from an alternative perspective.

UKRI Gateway to Research · FY 2025 · 2025-04

The field of synthetic biology enables industrial chemicals that are currently derived from unsustainable fossil fuels to instead be manufactured from sustainable feedstocks by living microorganisms. However, the diversity of chemicals that can be accessed via this approach is currently limited to molecules that have evolved in nature. Accessing 'non-natural' chemicals that we need to manufacture our clothing, medicines and many other every-day products is a current limitation of this emerging new technology. Project MICROCAT aims to address this limitation by developing biocompatible chemical catalysts that can perform non-natural reactions under bio-relevant conditions, and then be transported inside of microorganisms and interfaced with metabolism to enable the biosynthesis of new-to-nature compounds in living cells. This new approach will rapidly increase the range of products that can be bio-manufactured in the future and will simultaneously contribute to defossilizing the chemical industry towards net-zero. To achieve this, project MICROCAT is working on three main objectives: (i) The intracellular transport and activity of chemo-catalysts within lipid droplet producing microorganisms. (ii) Fully integrating biocompatible reactions with cellular metabolism to create self-propagating metabolic circuits. (iii) The scale-up of chemo-enzymatic processes in engineered microorganisms. During Phase 1 of this Future Leaders Fellowship, various new biocompatible reactions were discovered and shown to react cooperatively with native and engineered microbial metabolism. During Phase2, these concepts will be extended to include the use of catalytically active transition metal catalysts within living cells, within active metabolic pathways, and within large-scale bioreactors.

UKRI Gateway to Research · FY 2025 · 2025-03

The problem. Proving  the efficacy of new drugs is very costly and time-consuming and both grow exponentially with each stage of development – preclinical,  first-in-human, then several phases of clinical trials. The pathway can take over  ten years and cost more than US$1Bn. Many drugs fail and are discarded along the way, resulting in a huge waste of time, resource, and money. This does not deliver parity of access to populations across the globe nor across the strata of society and is severely constraining the rate of new drug development. This is especially true for drugs targeting infection and inflammation as the antibiotic pipeline is diminishing due to the huge costs for new drug development using outdated methods and trial methodologies. A potential solution. One way forward lies in an approach called “Intra target Phase-0/Microdosing”. “Phase-0” occurs very early in the drug development cycle, before the longer and more expensive phases. “Intra target Microdosing (ITM)” involves administering a tiny amount of drug to a microscopically small region of the body and measuring any therapeutic benefit at that point. There is  no wider systemic safety risk to the subject.  When accomplished effectively, ITM  can reject poor candidate drugs and raise confidence in the later success of promising drugs resulting in substantial savings of time, resource, and cost for drug developers and a more efficient pipeline of effective drugs becoming available to the population. Our contribution. ITM, while promising, is at a relatively early stage of development.  We have already, delivered multiple ITM studies , but have been limited by the underpinning measurement technology. One of the main factors limiting the rate of uptake is the capability of the techniques required to deliver a precise microdose to a specific location in the body then to measure the effect of that microdose later at the same location. This shortcoming must be addressed to unleash the potential of ITM. MicroTex will help bring this about. First by leading the way – pursuing its own pioneering research to begin solving the problems by developing and optimising an initial set of scientific and engineering techniques to improve ITM in a small number of exemplar organs (we have selected the lung and the eye). We have the expertise and track record required to progress these technologies into human studies. Second by making the case for ITM by actively partnering and networking to bring more players to the table – persuading members of the wider scientific and engineering community to participate in expanding the range of techniques available, and the number of conditions and organs addressed, alongside pharmaceutical companies and Phase-0 international networks. Third by developing a people-centric research environment with embedded training capacity so that researchers and other professionals can access the knowledge and skills necessary to effectively implement the new multidisciplinary approaches thus allowing their use to spread rapidly. This will all be enabled and augmented through deep engagement with patients and the wider population to explain the benefits, risks, and limitations, take on board their concerns, and work together with them to achieve the best solutions. Our mission. Through development of a new toolset to increase the performance of ITM , we will bring about a positive transformation of the drug development pipeline, that will be of huge and long-term benefit to mankind.

UKRI Gateway to Research · FY 2025 · 2025-03

Proteins and the nucleic acids DNA and RNA are the most fundamental building blocks of life and all living matter is either composed of proteins or substances produced by proteins. Proteins are chains of amino acids consisting of the same pool of 20 canonical amino acids. They are defined by the sequence of amino acids within the chain, a sequence that is encoded in DNA. The genetic code is the cipher that links the nucleotide sequence in DNA with the amino acid sequence in proteins. Genetic Code Expansion (GCE) is a ground-breaking genetic technology that gives cells the ability to expand the number of different amino acid building blocks at their disposal for making proteins. The additional amino acids, called non-canonical amino acids (ncAA), are chemically synthesized 'designer' amino acids with properties not found in nature. The addition of ncAA to the natural amino acid repertoire offers the ability to install entirely new functionalities into proteins, enabling customization for specific research goals. It is for example possible to introduce optical switches, bioorthogonal linkers to attach other molecules, or post-translational modifications. Despite the inherent power of the technology, its adoption as a research tool, especially in complex organisms like animals, has been held back thus far by low efficiency. We have recently solved this problem for the nematode worm C. elegans, where GCE is now robust, efficient, and ready for routine applications. The next step, and the objective of this proposal, is to apply our improvements to mice and make the technology accessible for fundamental and biomedical research using animals other than C. elegans. To demonstrate the broad utility of GCE across diverse animal systems our first target will be neurons in mouse brains, where numerous hypotheses related to the brain's inner workings await to be tested. We aim to use optimised GCE to develop new types of genetic tools that will allow introducing genetic modifications to neurons which can in real time be identified based on their functional or dysfunctional properties. Light mediated targeting of these select neurons will allow precise genetic changes leaving the environment of the neuron intact. This will allow testing how modification of key genes can impair or repair neuronal function in intact systems. The advancements we hope to make here are expected to overcome current efficiency barriers, making GCE technology widely accessible and unlocking its full potential for scientific research and discovery.

UKRI Gateway to Research · FY 2025 · 2025-03

This Place Based Impact Acceleration Account (PBIAA) aims to incorporate university research strengths in offshore wind engineering into the Forth and Tay region to address challenges in the areas of design and manufacture of fixed and floating wind systems, the development of a workforce, and the delivery of large offshore energy infrastructure projects. The Lead Civic Partner Forth & Tay Offshore (FTO) is a place-based supply chain cluster, established to drive the growth and implementation of offshore renewable energy on the east coast of Scotland. It's vision for 2030 is for the region to address the timely opportunity to become home to a thriving, comprehensive, internationally competitive offshore energy supply chain serving local, national and international projects. This proposal has been co-designed with FTO via a rigorous consultation process, to identify the needs where the region can benefit most from the expertise of the university partners, and where partners outside the consortium can be involved to augment this expertise further. This PBIAA aims to establish the partnership mechanism, then accelerate and grow the impact of academic research into the cluster, particularly in the areas of offshore and geotechnical engineering, manufacturing, operations and maintenance as well as the environmental and social aspects of offshore wind. It has a number of objectives (see Table 1) and activities (see Table 2).