University of Manchester

UKRI Gateway to Research · FY 2025 · 2025-02

This project collaborates with Quilombola communities to analyze biodiversity data gaps in Amazonian conservation areas. Utilizing their traditional knowledge, we identify key animal and plant species crucial to their lifestyle and evaluate their role in ecosystem preservation amid socio-ecological challenges. Employing traditional methods and modern technologies like DNA barcoding and remote sensing, we comprehensively record biota and landscape features. Guides integrate this data with scientific literature, focusing on species important to Quilombola communities. We aim to develop automated systems for community based biodiversity measurement, involving Quilombola communities throughout the research process. Specific objectives include promoting conservation, strengthening relationships, empowering communities, and enhancing research capabilities.

UKRI Gateway to Research · FY 2025 · 2025-02

ce formation and growth is a problem wherever sub-zero temperatures exist, requiring antifreeze/cryoprotectants, spanning in aerospace, renewable energy, vaccine delivery, biomedical research and the food industry. Anti-icing strategies currently deploy unsustainable practices, using large volumes of solvents to di-ice planes, to using methane-gas burners to prevent vineyards from freezing, to emerging cell-based therapies which urgently need advanced cryoprotectants to supplement DMSO-based freezing methods. Ice binding proteins have shown potential to transform how low-temperatures are mitigated in a range of academic and industrial challenge areas, but are simply not available at scale, nor a practical price point. Current polymeric mimics of IBPs have been shown to be potent, but are obtained by unsustainable methods, and are not degradable. In this proposal we will address the challenge of how to deploy the favourable properties of ice binding proteins, but using sustainable and degradable synthetic polymer mimics. Synthetic poly(amino acid) materials expertise at RCSI will be combined with UoM expertise in biomacromolecular mimics of ice binding proteins and polymer-sustainability, to discover the next generation of polymeric 'antifreeze' agents that are resorbable and/or degrade in the environment. Our goal is to first understand the structural requirements to retain ice recognition/modulation in chemically-simple poly(amino acids). We will then develop sustainable strategies for their upscaling focussed on both production by step-growth synthesis (with integrated life cycle analysis) as well as end of life (degradation): a cradle to grave, not cradle to gate approach. We will deliver future environmental and industrial impact by showing their function as anti-icing agents and the storage of cell-based therapies and quantitative, critical, life cycle analysis considerations. We will also upskill the researchers with critical, and authentic, sustainability skills. Our specific objectives are: 1. Use N-carboxyanhydride (NCA) polymerisation as a discovery tool to obtain precision poly(amino acid)s based on polyproline (PP) II and alpha helices. 2. Map the polymer/ice binding activity relationships to identify core structural motifs which are essential to activity. - Show biodegradation under hydrolytic, microbial and in vivo relevant conditions, to identify the material (from Obj. II) which is most ideal for diverse environments of release. 1. Demonstrate scalable synthesis of the most active materials using step-growth/condensation polymerisation, which is an industrially relevant method, used for e.g. Nylon preparation 2. Use polymers in model application areas of cellular cryopreservation, anti-icing and reduced ice-adhesion application areas. 3. Quantify impacts through life cycle analysis of the materials to understand, and mitigate, their impact.

UKRI Gateway to Research · FY 2025 · 2025-02

Monasteries and rulers were not only entangled but fully interdependent in the Carolingian Empire (a polity encompassing much of Western Europe from 751-888). Rulers sought to regulate the practices of monastic life, while at the same time depending on monastic resources; monasteries sought to secure royal patronage and to shape royal policies. Yet these relationships diverged along gendered lines: while female monasteries were largely treated as Carolingian familial resources, abbots of male monasteries exerted significant agency in building institutional relationships with royal power. This study will underscore the gendered foundations of Carolingian monasticisms and provoke a reappraisal of Carolingian 'patrimonial' rule, in which royal authority, far from being vested solely in the person of the ruler, was actively constructed and deployed by male monastic communities. This project will proceed in three strands, the first of which is based around my individual research programme; this will result in a sole-authored research monograph, peer-reviewed article, and four conference/seminar papers. Second, I will co-lead an international collaboration, which will take the form of two closed workshops, presentation at a public conference, and the preparation of a peer-reviewed edited volume (to which I will contribute a book chapter and a co-written introduction). Both of these research-focused strands will allow me to develop my research profile and to expand and consolidate research networks; the collaboration will further enhance my skills in research leadership. Third, and finally, this project will include a substantive public engagement strand. This will centre around the design of a major exhibition at the John Rylands Research Institute and Library on the theme of 'Church and State: from Charlemagne to King Charles'. While this is due to open to the public in autumn 2026 (soon after the conclusion of the grant), the intellectual work to design and organize the exhibition (and its accompanying events) will take place during the period of funding. During the period of the grant, I will also work with an educational consultant to design materials for A-Level educators and students in Religious Studies, here drawing on exhibition materials; I will also organize and design Widening Participation workshops for A-Level students from the Greater Manchester area (to be held at the Rylands in autumn 2026 during the period of the exhibition). This research-led public engagement programme will present cutting-edge research, highlighting its relevance to current issues and debates.

UKRI Gateway to Research · FY 2025 · 2025-02

Effective and robust medical technology and pharmaceutical testing and approval processes are critical to public protection, enhanced health and wellbeing. However, existing human and animal trials have high failure rates and can frequently lead to negative consequences for patients. They also add time and cost to the delivery of new treatments and devices (typically eight years and 30% of costs for a pharmaceutical product). A growing body of evidence suggests that ln-silico Technologies {i.e. computational modelling and simulation techniques used across medical product R&D lifecycles) could radically improve medical product testing, trials and assessment processes, providing significantly increased reliability while reducing time and costs. This would directly benefit patients by reducing failure and recall rates for new medical products, and would generate economic growth by stimulating innovation in businesses developing pharmaceuticals and medical technologies. However, the use of evidence from in-silico technologies has not yet been integrated into regulatory processes. Our aim is to address this deadlock by establishing a UK Centre of Excellence on in-silico Regulatory Science and Innovation (UK CEiRSI) to develop tools, standards, and best practices for integrating evidence from computational models into the regulatory process.

UKRI Gateway to Research · FY 2025 · 2025-01

Goal The goal of this project is to develop a new approach to evidence review: Interdisciplinary Systematic Review (ISR). ISR will provide a way to integrate mechanistic evidence from across disciplines, alongside the studies that are the focus of orthodox systematic reviews. Background Synthesising research evidence is key to evaluating the effectiveness of interventions and to developing policy. The dominant approach in medical disciplines, championed by the Evidence-Based Medicine movement and Cochrane, appeals to an explicit evidence hierarchy in which randomized controlled trials (RCTs) are seen as having inherent advantages over other forms of evidence. Other disciplines and fields have begun to emulate this approach, producing 'evidence-based education', 'evidence-based management', 'evidence-based policing' and more. But the RCT design has significant weaknesses if used in the absence of mechanistic evidence—evidence about the causal mechanisms by which interventions produce effects. The assumption that RCT evidence can stand alone led to untrustworthy conclusions about the efficacy of masks during the COVID-19 pandemic. The lead applicant, a philosopher, has already published a preliminary outline of how mechanistic evidence might be combined at a philosophical level with RCT evidence. This project seeks to take that work forward with a team of experts drawn from multiple disciplines (including medicine, law, policy, statistics), using a review of the effectiveness of face masks as a worked example. Research questions How can mechanistic evidence be systematically and rigorously combined with RCTs and other designs to produce a more interdisciplinary and robust evidence base for evaluating intervention efficacy? What are the strengths and limitations of this new approach ('Interdisciplinary Systematic Review', ISR) compared with other mechanism-sensitive (theory-based) review methods such as realist or metanarrative review? Study design Interdisciplinary desk research to develop and apply a novel systematic review methodology, combining insights from analytic philosophy, Bayesian statistics and theory-based systematic review.

UKRI Gateway to Research · FY 2025 · 2025-01

The early developing embryo is a complex dynamic environment. During development, individual cells within the embryo must respond appropriately to a multitude of 'signals' to yield distinct cell types, e.g., neurons, muscle cells and bone to form our body's organs and structures e.g., brain, heart, and skeleton. Currently, how immature embryonic cells 'decide' their fate is not fully understood. Precise control of such developmental processes is encoded in the genome in the form of multifactorial gene regulatory networks. However, how cells interpret external signals to activate internal cell-type specific gene regulatory networks is not clear. This problem is exemplified in the neural plate border (NPB). The NPB is a discrete, transient region of the early developing embryo. Cells within the NPB region are multipotent, meaning they give rise to a number of different cell types and tissues. Specifically, NPB cells generate neural crest and sensory placode cells. Neural crest cells in turn contribute to a wide range of derivatives in the vertebrate body, including elements of the peripheral nervous system, parts of the heart, pigment cells and the craniofacial skeleton. While placode cells form the cranial sensory structures, nose, ears, and lens. Defects in the development of the neural crest and sensory placodes are associated with one-third of all congenital birth defects including cleft palate and other facial abnormalities. As well as a number of syndromes including DiGeorge, which presents in defects in the thymus and thyroid glands together with heart problems, and Hirschsprung syndrome which manifests in the intestinal nervous system resulting in defects in gastrointestinal tract movements. Furthermore, a number of cancers are known to arise from neural crest derived structures such as melanoma, neuroblastoma, and glioma. It is not known how the NPB is endowed with such unique multipotency and, when and how individual NPB cells are directed towards different lineages (i.e., neural crest or placodes). Tackling these questions has proved challenging due to the sparsity and transitory nature of NPB cells. However, with the advent of next-generation single-cell technologies and genome engineering tools it is now possible to address these questions. I plan to combine next-generation single-cell 'Multiomics' with innovative developmental biology techniques I have adapted, to resolve the complexities of cell fate decisions from the NPB. In particular, I will determine the combinatorial action of signalling molecules, transcription factors, and regulatory elements comprising the complex gene regulatory networks that direct NPB cells towards specific fates. I will conduct my research using the chicken embryo which is an excellent model for developmental biology owing to its accessibility, affordability, and similarity to human embryo development. I will extract NPB cells from chicken embryos using genetic tools I have previously developed. I will then perform single-cell 'Multiomics' experiments with isolated NPB cells to generate gene expression and regulatory data, from the same cells. I will integrate and functionally validate these datasets to reconstruct gene regulatory networks underlying NPB cell fate decisions. Unravelling the intricate mechanisms driving cell fate decisions will help us to understand the underlying cause(s) of disease as well as identifying potential targets for therapeutic intervention. Also, due to their unique multipotency, there is broad interest in using NPB cells in stem cell-based treatments. Identifying the molecular mechanisms and interactions underlying NPB development will facilitate development of efficient, targeted, protocols for this purpose.

UKRI Gateway to Research · FY 2025 · 2025-01

The role of evolving preferences over consumption goods has long been understood as a determinant of the pattern of structural transformation. However, the role that will be played by consumption preferences over particularly 'green' and 'brown' goods during the required climate transition is less well understood. The climate transition is also a 'structural transformation' problem - an issue of evolving sectoral structure -- and there is scope for extension of traditional analysis from development economics and development studies to the emergent problem of realising a just and developmental transition. Among the important socio-economic and political considerations for key stakeholders to ponder in driving forth climate action are the following issues: 1) that consumption preferences are likely to differ depending on where an individual sits in the income distribution; 2) that there may be conflict within firms over the choice of production technique since this influences the energy-intensity and emissions path of production; and 3) that workers and firm-owners, as well as other actors, influence the political process as voters, independent of their respective roles in consumption and production. In short, there are significant behavioural elements to the climate transition that require better empirical and theoretical understanding. Without understanding this behaviour, strategising a just and developmental transition to a greener economy is impossible. The central objective of this research is correspondingly to strategise how to reconcile structural transformation (raising the share of manufacturing production in total output) with the just transition. Given the historic energy intensity of manufacturing, this will be no mean feat, but it is surely one of the central global challenges for environmental activists, trade unions, policymakers -- and academics to strategise today. To do so, we aim to generate new empirical and theoretical insights into how preferences over consumption, production techniques, and voter behaviour impact the climate transition. Specifically, using the Brazilian context as an initial starting point, our research will help better understand preferences and behaviour in developing countries regarding these three crucial dimensions to the just transition. The research will consist of a survey investigating individual behaviour in each of these three dimensions and heterogeneity in behaviour along these dimensions. The objective of the research is to channel knew knowledge about behaviour of the aforementioned key actors to policy-relevant insights that can inform emboldened climate action for trade unionists, environmental activists, central bankers, treasury officials, and presidencies. The potential benefits could not be greater; a policy and political regime geared toward a reconciled vision for economic emancipation and climate action in the parts of the world in greatest need.

UKRI Gateway to Research · FY 2025 · 2025-01

Climate change has catalysed a worldwide search for renewable and sustainable products to replace oil-derivatives. One quarter of the global greenhouse gas emissions come from the transportation and chemicals industry, and there is a strong desire to find alternative fuels and chemicals, which can be produced with environmentally friendly processes. One possibility is the use of genetically modified microorganisms grown on renewable feedstocks to produce fuels and chemicals by fermentation. Of importance is the production of branched-chain alcohols, namely isobutanol, a desirable next-generation biofuel, suitable for a multiproduct biorefinery. Isobutanol is quite toxic to the production microorganism, and depending on the concentration, it can inhibit cell growth completely, or affect cell physiology in a way that lowers the yield and total amount of isobutanol produced. Yeasts belonging to the Saccharomyces genus can hybridise readily, creating first-generation (F1) hybrids with unique phenotypes enabling them to survive and proliferate in the stressful environments, and hence can be considered as potential microbial hosts for industrial processes. Hybridisation provides a novel source of variation for evolution to act upon, leading to adaptations that could not occur in either parental species. The problem with the development of inter-specific hybrids is that, although they are viable and sometimes fitter than the parents, they are sterile, and hence not genetically tractable. An example from Aristoteles's time is the hybrid between a female horse and a male donkey, namely the mule, which is a healthy animal employed in several human activities but cannot produce any offspring. Adaptive Laboratory Evolutionary (ALE) experiments, where a microbial population is evolved under a specific pressure to select for fitter progeny, has only been carried out on specific strains or sometimes on F1 hybrids. Although the F1 hybrids contain all the genetic diversity of the two parents, there is no recombination and random segregation of alleles, as it would happen after meiosis where specific parental traits are distributed in the offspring in different combinations and can give rise to different phenotypes. In our lab, we were able to overcome hybrid sterility by duplicating the genome content of the diploid F1 hybrids, making them tetraploids. Such tetraploid lines could undergo meiosis and so we were able to create F12 progenies with a large and diverse combination of traits. Here, we propose to use ALE to evolve F12 hybrid lines and their parents, for tolerance to isobutanol. The objective is to identify specific genotypes with high tolerance to this branched-chain alcohol, and to develop new potential production hosts. Furthermore, we will demonstrate that the higher genetic diversity, engrained in the ancestral F12 population, increases the microbial adaptation potential, and leads to a larger pool of extreme phenotypes in the evolved F12 hybrids compared to the evolved parents. We plan to sequence the genome of the best candidates and to study their gene expression to identify genes, promoters, and pathways that are responsible for the isobutanol tolerance trait. We will genetically re-construct in the parental strains a selection of genetic variants, identified in the evolved F12 population that are resistant to isobutanol, to validate their phenotypic effects. Lastly, we will grow the evolved high tolerant hybrids in the presence of other toxic compounds of industrial relevance to see whether they acquired some cross-protection to other branched-chain alcohols or whether, due to the acquired adaptation to isobutanol, they lost the ability to grow efficiently on other inexpensive renewable substrates. Ultimately, the more valuable hybrids will be those that have acquired isobutanol resistance with the least trade off in other relevant industrial conditions.

UKRI Gateway to Research · FY 2025 · 2025-01

Electron Paramagnetic Resonance (EPR) spectroscopy, also known as Electron Spin Resonance (ESR), is possibly the most powerful technique for characterisation of paramagnetic materials, i.e. that contain unpaired electrons. Unpaired electrons give rise to the magnetic and electronic properties of materials and often govern reactivity when present, hence understanding their environment and behaviour is important. Paramagnets are ubiquitous from biological processes to magnetic materials; hence EPR is an essential tool in physics, chemistry, materials and biological sciences. The EPSRC funds a National Research Facility (NRF) for EPR, located in the Photon Science Institute (PSI) at The University of Manchester (UoM), providing access to state-of-the art experimental techniques and expertise for the UK academic community. Crudely, there are two ways to do EPR spectroscopy: continuous wave (cw) EPR and pulsed EPR, which give complementary information. Our two previous successful core equipment grants have been used to enhance the capabilities of pulsed EPR in the NRF. This proposal is designed to markedly enhance continuous wave capabilities and capacity, through two related strands: (i) The newly commercialised multi-harmonic detection system will provide enhanced sensitivity, and its modular nature will allow it to be used across all five microwave frequencies that we currently operate: L-, S-, X-, K- and Q-bands (spanning 1-34 GHz). This will enable more ready study of samples with low spin concentrations or that are sample-limited, and it will shorten acquisition times for “normal” samples. It will also make study of lossy dielectric samples (e.g. higher water content) more straightforward. (ii) A self-contained benchtop spectrometer system will significantly enhance capacity for cw X-band measurements.  X-band is the most common screening frequency, and it is the frequency most commonly used in research applications. In addition, the kit will have new benchtop capabilities for sample cooling between 300 and 5 K (using an existing closed-system cryostat), transient signal detection, and multi-harmonic detection [item (i)]. Our current benchtop system is operating to capacity. Moreover, because the benchtop system is portable it will also enable us to take high-end research capability in cw EPR ‘on the road’, including for outreach and training events, and also to measure ‘difficult’ samples in the users’ own laboratory, where those samples are under greater control than if they were brought off site to the EPR NRF. Benchmarking in this way will then allow much greater confidence in results when those samples are subject to more detailed measurements at the NRF. A particular example of off-site use is for medical samples in a hospital, which is currently being negotiated with a user of the NRF. These extensions to multi-harmonic detection and expansion of state-of-the-art benchtop EPR capabilities will increase the capacity for EPR for all users of the NRF across the UK, including ECRs and doctoral students, and the new capabilities will widen the user base. To contact the National EPR Facility and Service, please email: epr@manchester.ac.uk and web-site: https://www.chemistry.manchester.ac.uk/epr/ EPR Team: David Collison (DC); Eric McInnes (EJLM); Alice Bowen (AMB); Floriana Tuna (FT); Muralidharan Shanmugam (MS); Adam Brookfield (AdB)

UKRI Gateway to Research · FY 2025 · 2025-01

Mission oriented innovation policies (MOIP) are a new generation of transformative policies aimed at fostering innovations that help address complex societal challenges. The uncertain, multilevel, and complex character of MOIP exacerbates the risk of policy failure, i.e., the risk of the policies not delivering their intended goals, leading to ineffective policy support and growing distrust towards governments. Despite this increased propensity for potential risk of policy failure, the nature of these risks and the appropriate approaches to mitigate them have not been analysed in the context of MOIP. Within a conceptual framework built upon risk governance and public policy research, we analyse policy failure risks in the design and implementation of MOIP and identify suitable risk governance approaches to address them. To do so we analyse specific MOIP initiatives with sustainability related goals in three selected countries (United Kingdom, Poland and Canada) using Qualitative Comparative Analysis (to identify necessary and/or sufficient links through systematic cross-case comparison) and Process Tracing (to construct key causal mechanisms at the within-case level). Based upon a review of the literature, we hypothesise that policy failure risks will originate through a lack of public actors' capabilities, internal and external coordination problems, stakeholders' motivations and incentive issues, and problems in the management and implementation of programmes. We also identify which risk management approach (risk informed, precautionary, cautionary, discursive and risk governance) is more appropriate for their mitigation. The research contributes to a better understanding of MOIP failure risks and their governance, which can in turn help reduce policy failure and increase levels of trust in institutions and public authorities.

UKRI Gateway to Research · FY 2025 · 2025-01

Graphitic components are subjected to fast neutron flux in a molten salt reactor (MSR) for several years and there is a potential for salt or fuel salt infiltration into the bulk graphitic regions. Salt infiltration is generally considered to be unfavourable or harmful to the operation of an MSR due to the potential for graphite degradation, transport of fission products such as 135Xe that can decrease moderation, generation of hotspots, and fuel inventory change. In general, salt permeation and transport, which are dependent on the salt thermodynamics and kinetics, depend critically on the pore/crack shape, morphology and interconnectivity that are not yet well-elucidated. We propose a suite of fuel salt (FLiBe with U) infiltration experiments followed by X-ray computed tomography, mechanical property evaluation, and high-fidelity data analytics and modelling along with complimentary porosimetry measurements and XPS analysis. Three graphite grades are selected in this project: NBG-18, IG-110 and POCO: ZXF-5Q; the selected grades will cover the typical porosities observed in nuclear graphite. The main objective of our investigation is to draw out the differences in fuel salt infiltration behaviour in the selected graphite grades and assess the change in mechanical properties. We anticipate that our work will assist in selecting nuclear graphite grades optimized for the current and advanced MSRs.

UKRI Gateway to Research · FY 2025 · 2025-01

Care is crucial for the maintenance of social connections that enable infrastructures to function. Care is needed to raise children, protect vulnerable people, sustain our well-being, and support older people. We are currently in a crisis of care, which undermines the foundations of everyday life and stretches communities to breaking point. The organisation of care through the state and the market has led to increasing inequalities that have been exposed by a decade of austerity, the pandemic, and the cost-of-living crisis. This brings into question the way that societies organise and resource care. The commons are based on the autonomous organisation of shared resources, which foregrounds radical forms of democracy and solidarity. The commons provide an alternative model for collectively organising care: the care commons. But despite this promise, these connections have not been systematically drawn on through academic or policy work. This project will position the care commons as 'resistant spaces' beyond formal institutions that can create a foundation for new urban ecologies of care. Social science can support learning about the commons to strengthen practices in resistant spaces. Creating a methodology that is oriented towards the commons remains a challenge that has not yet been fully addressed. Pragmatism provides a philosophical foundation to support learning about the commons. It is a paradigm for inquiry that is geared towards learning through experimental practices that are designed to address social problems. But pragmatism is associated with incremental improvements. The project will overcome this limitation by creating an original operational philosophy of 'situated utopian pragmatism' that uses social science to connect concrete issues of the everyday, experimental practices, and abstract thinking about the commons. Critical participatory action research (CPAR) surfaces everyday knowledge and leverages the strengths of critical theory and social science research to support social action. This project will use CPAR to operationalise situated utopian pragmatism to learn about the commons. It will inform the field of participatory research by generating much-needed theoretical innovation. CPAR will be used through three case studies. The first case study will explore the survival programmes of the Black Panther Party (BPP) to develop the concept of situated utopianism. The BPP autonomously organised care in everyday life, while providing a critique of inequalities in the hope of transforming them. The concept of situated utopianism will inform two case studies of organisations in post-welfare 'second' cities of the global north: Manchester and Thessaloniki. There will be four learning projects undertaken in each city: firstly, a local people's history project to define the idea of resistant spaces; secondly, a photovoice study that examines the organisations' practices as a response to the crisis of care; thirdly, participatory workshops to explore future alternatives of the care commons that 'bring back' learning to improve the organisation's strategies; and fourthly, exhibitions that bring all the resources together to inform policymakers and communities. The second case study in Manchester will develop the approach. The third case study in Thessaloniki will refine the approach and ensure that it is operational. This project will create enduring impact by improving practice and leaving an infrastructure for future activity through the case study organisations, producing creative outputs, and catalysing city-wide networks to develop the commons. It will contribute knowledge to a nascent agenda on the care commons and guide activists and academics working towards social transformation.

UKRI Gateway to Research · FY 2025 · 2025-01

The healthy lung contains only sparse immune cells to allow the physical properties necessary for efficient gas exchange and maintain its critical functions. In chronic lung diseases, such as chronic obstructive lung disease (COPD), immune cell infiltrates expand, persist and contribute to defective lung function. As a result, the lung does not return to its original state, and this can have long-term consequences for the patient. COPD is the third leading cause of death worldwide, with no available treatments to delay disease progression. Therefore, developing novel therapeutic strategies for improved disease management is a global priority. Recent studies have focussed on understanding the profile of lung-infiltrating immune cells and their contribution to COPD. Remarkably, knowledge of B cells has lagged far behind that of other immune cells, despite their accumulation and persistence in the COPD lung. This UKRI FLF aims to uncover how B cells promote COPD pathogenesis. Do lung-infiltrating B cells promote tissue inflammation and airway remodelling? Do these aberrant B cell responses associate with disease severity? Can we harness novel pathways involved to develop improved treatment approaches for patients? To address these central questions, I will study in detail the interactions between B cells and their surrounding cells and matrix, to understand how these communications either exacerbate or limit disease. Using freshly isolated immune cells and tissue sections, as well as mouse models of COPD, I aim to ask the following key research questions: - Which aspects of B cell responses in COPD patients associate with disease severity? - Can we identify a molecular signature of COPD-associated B cells in the lung and periphery of COPD patients? - How do interactions between B cells and the surrounding lung microenvironment influence disease outcomes? - Can we ameliorate disease by targeting novel pathways driving B cell dysfunction? This work will be done at The University of Manchester within the world-leading Lydia Becker Institute of Immunology and Inflammation in collaboration with clinicians and pathologists at Manchester University NHS Foundation Trust, as well as my research partners in the UK and overseas. Improved understanding of B cells in COPD could open novel therapeutic avenues for better disease management. These findings may also benefit patients with other chronic lung diseases, such as asthma.

UKRI Gateway to Research · FY 2025 · 2025-01

Context: The salt system FLiBe is considered to be one of the two options for the blanket material for breeding tritium fuel in the UK's STEP fusion reactor to be deployed by 2040, and is considered for use in a number of next generation molten salt reactor (MSR) fission designs, primarily because of the favourable neutronic properties of this salt system. However, despite its proposed deployment in looming advanced nuclear energy systems there is comparatively limited fundamental understanding of the chemical behaviour of these salts under likely operational conditions and associated performance knowledge for FLiBe containment materials. Challenge: There are few facilities throughout the world capable of studying FLiBe salt systems not only due to the challenges of preparing and handling fluoride salts, due to the potential generation of corrosive hydrofluouric acid (HF), but also the toxicity concerns in handling beryllium. The ability to safely study FLiBe with radioactive tritium to support fusion, and other radioisotopes of interest (e.g uranium and thorium for MSR systems) will make this facility unique worldwide. Aims and Objectives: The proposed glovebox system, combined with an integrated worker safety and monitoring strategy, will offer world-leading capability of high immediate interest across academia and industry, which is needed given the relatively short timelines to deployment of these FLiBe salts in advanced reactor systems. The primary aim of the proposed equipment is to provide the capability to handle FLiBe molten salts, that minimises the risk of user exposure to Be toxicity and the possibility of HF generation.

UKRI Gateway to Research · FY 2025 · 2025-01

Reproductive behaviors and their regulation are most fundamental to all animals. Since they are largely hard-wired into the brain we can learn how behavior is encoded in the brain and shaped by perception and decision-making processes. Understanding how behavior is encoded in the brain is one of the big challenges in biology and requires a behaviorally and genetically tractable model organism. Female reproductive behaviors of the fruit fly Drosophila melanogaster profoundly change after mating leading to refusal to remate and induction of egg laying. Male-derived sex-peptide (SP) is the key molecule inducing these post-mating behaviors, which can last up to one week in the presence of sperm. This very robust behavioral response of Drosophila females to sex-peptide provides the essential prerequisites to map SP responsive neurons and eventually learn how complex behaviors such as mating choice and control of egg laying are encoded in the brain. A key tool to find SP-target neurons is membrane-tethered SP (mSP), that will induce a response when the same neuron that expresses mSP also expresses an SP receptor. Our recent studies showed that there are several distinct neuronal populations that can via exposure to mSP induce refusal to remate and egg laying. Importantly, we could also show that these two post-mating responses can be separated by mSP expression either in the trunk or in the head leading to induction of egg laying or reduction of receptivity, respectively. These exciting findings draw a much more complex picture how SP interferes through multiple sites with female reproductive behaviors to coordinate the post-mating response, yet how this works at a brain systems level remains to be elaborated. We currently have very limited understanding of where SP-target neurons are located in the fly brain. To identify the neuronal circuitry underlying the sex-peptide response, we have used expression of mSP in subsets of neurons of genes involved in the SP-response and the sex-determination pathway. In particular, we subdivided the regulatory region of the broadly expressed SP receptor (SPR) gene into small regulatory fragments expressing only in subsets of neurons. Using this paradigm-shifting approach we have identified small populations of neurons, one that reduces receptivity and induces egg laying, and another one that only induces egg laying upon expression of mSP. Through these experiments we now have worked out, in principle, how to identify all the different populations of SP target neurons. Hence, we now need to identify small regulatory fragments in sex determination genes and SP response pathway genes to identify additional SP target neurons. These experiments will be then be the resource to identify the relevant neurons in the recently become available high-resolution Drosophila brain from the fly connectome project to build the circuitry directing the female post-mating response. With these experiments we will test the hypothesis that SP-target neurons are present at multiple sites in the brain to direct female reproductive behaviors for a coordinated post-mating response. Compared to a previous model arguing for central induction of all PMRs, a modular assembly of individual PMRs holds evolutionary flexibility during speciation and adaptation to diverse habitats, but can maintain basic regulatory principles such as the control of egg laying. We therefore anticipate that the knowledge obtained from our studies will be applicable to a wide range of pest insects pinpointing towards novel strategies for pest management to protect crop and control insect born diseases by interfering with egg laying. In particular, our findings are directly transferable to the close relative Drosophila suzukii, one of the few species able to lay eggs into fruits, which is currently invading Europe including the UK and causing damage in billions to fruit production.

UKRI Gateway to Research · FY 2025 · 2025-01

Microbial communities (often called microbiomes) are everywhere; on our skin, in our gut, in the soil we rely on to grow our food, indeed in almost every habitable environment on the planet. Members of microbiomes interact with one another in myriad ways which we are only just beginning to appreciate, thanks largely to powerful new tools at our disposal. In this ambitious, multidisciplinary project, we bring together expertise to use these tools to unearth the 'rules of life' that govern the interactions between microbial community members, with the view to develop predictive approaches that can help us to understand and control microbiome function. Drawing on low diversity communities that inhabit geothermal springs, we will interrogate the metabolic, ecological and evolutionary interactions between community members that collectively govern the conversion of CO2 into value-added products. These products span primary metabolites that result from direct microbial growth (and hold value as platform chemicals for manufacturing industries and as biofuels), as well as secondary metabolites that are not directly liked to growth but that play ill-defined roles in microbial communities, and often harbour bioactive properties of high value to society (e.g. antibiotics, anticancers). We will use synthetic biology approaches to engineer the microbiome and its metabolic pathways of interest, both as a learning tool with which to test hypotheses on metabolite production and function, and as a means to augment the CO2 bioconversion capacity of the system for future biotechnological development. In parallel, we will apply ecological and metabolic modelling approaches to continue to generate hypotheses that can be tested with our model system, and which will be integrated into new predictive tools to accurately infer function from microbiome genomic data. Crucially, these approaches will work in tandem to help resolve the microbe-microbe interactions that drive this model system, which we have deliberately chosen to maximise the success of our ambitious goals. By unravelling the rules of life in these low-diversity systems, we will take the first major step towards understanding the more complex communities that impact our ability to grow food and live healthy lives. At the same time, our project promises to deliver new ways to turn waste CO2 emissions into waste, towards a more sustainable and Net Zero future.

UKRI Gateway to Research · FY 2025 · 2025-01

The selective and sustainable formation of important bonds is crucial for the assembly of society's pharmaceuticals, agrochemicals and materials. Metal-catalysed cross-coupling is now routine in every chemistry laboratory and plant worldwide and the positive impact on science and society has been remarkable. Unfortunately, the majority of these cross-coupling reactions are mediated by platinum group metals (e.g. Ru, Rh, Pd, Ir and Pt). The environmental and socio-economical cost of extracting such metals from the earth's crust presents grave consequences, a fact only reinforced by their dwindling supply; this makes their use unsustainable and our reliance on them simply cannot continue. Inspired by work by the Procter group and others, I believe that the widely-abundant element, sulfur, can replace metals in cross-coupling by; (i) activating chemical feedstocks, and subsequently, (ii) generating reactive intermediates for carbon-carbon and carbon-heteroatom bond formation. More specifically, I will use sulfonium salts - generated in situ from simple, otherwise inert, feedstocks - as coupling partners and reagents for new metal-free catalytic cross-couplings driven by visible light, that also offer new and improved selectivity profiles when compared to traditional metal-catalysed processes. My overarching aim is to discover new visible light-mediated, metal-free coupling platforms through the innovative merger of; 1) in situ sulfonium salt formation, and; 2) EDA complexation chemistry employing simple, catalytic organic molecules for photoactivation. The three proposed 'concepts' in the action, involve the photochemical functionalisation of important benzothiophenes, amides, and alkyl halides. My high-risk and ambitious studies will deliver prototypical processes that will pave the way for future coupling processes that can't currently be achieved in a sustainable fashion or are simply not yet possible.

UKRI Gateway to Research · FY 2025 · 2025-01

The overall objective of this proposal is to assist in the construction of the Square Kilometre Array (SKA) telescope. The SKA is made up of two telescopes, MID and LOW, each being an interferometer comprising a large number of receiving elements: in the case of MID, reflective parabolic dishes, and in the case of LOW arrays of dipoles. The specific objectives to be pursued by the University of Manchester are as below. - To develop a system for the Pulsar Search capability of the SKA LOW and MID telescopes under the SAFe framework. This involves delivery of highly efficient software for the discovery of pulsars and time-domain fast radio transients. - To develop the MCCS component of the monitor and control system for the SKA-LOW telescope under the SAFe framework. - To provide scientific, technology, engineering and management advisory services to all stakeholders involved in the development of the SKA Synchronisation and Timing systems.

UKRI Gateway to Research · FY 2025 · 2025-01

Ion mobility-high resolution mass spectrometry (IM-HRMS) is the next-generation analytical platform in research and industry. Unlocking its full potential across applications as varied as biotherapeutics, environment and food safety requires not only pushing back the frontiers of instrumentation, fundamental understanding and applications - but harmonisation is essential. To achieve this, current shortcomings in data collection, analysis and reporting across instrument types, laboratories and research areas need to be scrutinised and overcome. The MobiliTraIN Doctoral Network will form 10 Doctoral Candidates (DCs) who will bring a new fundamental understanding of IM- HRMS, provide reference materials and guidelines for standardisation, develop state-of-the-art methods for the application of IM- HRMS in biopharmaceutical development, biological 'omics studies, and nontarget screening of contaminants, and lay the foundations for IM-HRMS adoption in industry. Through an interdisciplinary research programme, including an open science approach and training in technical, business and transferable skills, the MobiliTraIN DCs will become leading experts in ion mobility with a unique skill set to successfully advance their careers while supporting Europe's innovation capacity. Building on existing collaborations and research excellence covering the entire innovation chain of IM-HRMS development and application, MobiliTraIN unites 8 academic institutions, 3 leading instrumentation companies, 1 regulatory agency, 1 pharma industry leader and 5 SMEs from 8 countries. With complementary expertise, know-how and mentoring experience, our consortium is ideally suited to unveil the potential of IM-HRMS as a key technology for safer therapeutics, better understanding of complex disease progression and improved monitoring of food, water and public health safety.

UKRI Gateway to Research · FY 2025 · 2025-01

The main goal of this project is to explore how "science diplomacy" (which means using scientific cooperation between countries or scientists to improve international relations) can be used to support democracy, good governance, and trust (DGT). The focus of our research is on the role metascientific observatories (which are organizations that study how science works, its outputs, and how research funding is distributed) can or could play in all of this. These observatories and their practices and outputs have an increasingly important impact on how science is measured and understood so it is really important to better understand them and how they might develop in ways which are more inclusive and supportive of good DGT. To do this, the project will use a range of different research methods to (1) study how science diplomacy connects to DGT; (2) improve our understanding of "metascience observatories" in order to see if they can help improve science diplomacy; and (3) find ways that metascience observatories might help tackle threats to DGT and to take advantage of opportunities they offer to DGT. The project will be carried out in three main stages (called work packages) with several smaller tasks, involving collaboration among international partners from seven countries: Brazil, Canada, France, Poland, South Africa, the UK, and the US. The teams have a wide range of research skills, which will help gather and analyze data more effectively, leading to stronger results. The project will produce scientific papers as a core contribution to improved knowledge, but it will also produce useful information for policymakers and stakeholders. It will also focus on building networks for science diplomats and offering training for early-career researchers. We are committed to promoting fairness both within our team and in the way we encourage the development of more inclusive metascience observatories. The project will also focus on sustainability in terms of inclusive metascience, ensuring that the network of observatories brings lasting benefits to society by improving the relationship between science and society and ultimately ensuring that everyone has equal opportunities to take part in the production of knowledge and to access and make use of that knowledge.

UKRI Gateway to Research · FY 2025 · 2025-01

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

UKRI Gateway to Research · FY 2024 · 2024-12

Since its creation in 2004, the University of Manchester has focussed on building its reputation for world-class research and innovation. Through substantial internal and external investment it has established an internationally leading research environment that supports our staff and students to address key challenges facing humanity in addition to pushing the frontiers of fundamental research. These are embodied within our institutional Research Beacons of Advanced Materials, Biotechnology, Cancer and Energy, and further within the Research Priority Areas of the Faculty of Science and. Engineering including Artificial Intelligence, Health, Quantum & Digital, Sustainability and ‘Fundamental’. It is of course no surprise that these are areas where National Strategies and Programmes exist and with EPSRC priorities. Within this context we propose to utilise the Core Equipment funding to support research aligned with our above priorities, allowing us to upgrade multi-user equipment that is at end of life, increase facility capacity and accessibility, and to support early career researchers in whom we have ourselves invested through our Dame Kathleen Ollerenshaw (DKO)  fellowship scheme. Based on our internal call, review and prioritisation process for capital equipment (managed by the Faculty of Science and Engineering) open to all academics, research fellows and research technical professionals, and parallel engagement with our 2024 DKOs, we have prioritised the following items for support by the 2024/25 ESPRC Core Equipment Funding: [1] NKT Stabilised Laser - The laser system will primarily be used in the new Quantum Engineering Lab at Manchester to develop acceleration sensors operating at the quantum limit. [2] Moku:Pro Multi-Inst – This will enable the development of a new generation of portable acceleration sensors operating at the quantum limit with high sensitivity and tunable bandwidth. [3] Gasometrix Mass-Spec - A portable mass spectrometer for quantification of He, Ne, Ar, Kr, N2, O2, CO2, CH4, H2 and other gas species in gases and water. [4] Magma M4 GPU - A GPU workstation, primarily consisting of 4 x NVIDIA RTX 6000 Ada GPUs, directly benefiting ECRs and doctoral students in AI-related fields. [5] Wavemeter/Switch - A High Finesse Wavemeter and 8-channel Photonic Crystal Switch enabling the simultaneous wavelength measurement of 8 lasers with an absolute accuracy of 60 MHz. [6] Credo Ti:Sapph laser - Providing continuously tuneable laser scanning between 690 nm and 950 nm supporting novel medical isotope separation and ion source development for radioactive ion beam facilities. [7] SRI Gas Chromatography - To allow the study of surface-chemically sensitive devices and materials, specifically metamaterials for catalysis and sensing [8] R&S Network Analyser - Supporting multiple use groups across the Faculty who are increasingly turning to the utilisation of microwave electronics from quantum technologies through to communications. [9] MHz-GHz RF Source - Delivering 8kHz to 40GHz continuous wave and timed pulses meeting demand for microwave characterisation by multiple communities, for example to study spin (de)coherence in quantum devices. [10] AXIMA MALDI-TOF - A direct replacement for an end-of-life Matrix-assisted laser desorption/ionization (MALDI) time-of-flight (TOF) mass spectrometry workhouse tool in chemical and biomolecular/biochemical research. [11] Device Analyser - Enabling characterisation of transistors and passive components used in microwave, millimetre-wave and submillimetre-wave MMIC circuits.

UKRI Gateway to Research · FY 2024 · 2024-12

Spatial communication is fundamental to our species. Spatial terms, including spatial adpositions and demonstratives, are among the most frequent terms in languages and form the key connection between language and objects/locations in the world. Yet little is known regarding how spatial communication changes as one ages in later life and across different spatial scales and media. The focus of SCALA is to understand fundamentally how spatial communication changes in typical and atypical ageing across spatial scales, and how technology may be harnessed to afford enhanced understanding of spatial communication and support for spatial communication when needed in the context of an increasingly ageing European population. This DN will train the next generation of scientists in the full range of multidisciplinary and cross-sectorial methods necessary to make significant progress in understanding human-human and human-technology spatial communication across time and scales, with direct synergies between basic research and application. Training is structured around two interdisciplinary research themes - Spatial Communication in Typical and Atypical ageing, and Spatial Communication, Technology and Ageing - both involving systematic co-supervision and collaboration across sites, with extensive interplay between academic and non-academic beneficiaries and associated partners. In turn we expect that a range of applications will be enhanced with increased usability, and with associated societal and economic benefit. The training of the cohort of Doctoral Candidate Fellows follows innovative PhD training approaches and will provide comprehensive interdisciplinary training, embracing leading peer assisted learning methods that have been successively employed in previous DNs. This will produce a cohort of unique and highly skilled researchers ideally equipped to add significant value to both the public and private sectors.

UKRI Gateway to Research · FY 2024 · 2024-12

Electrical power systems are undergoing unprecedented changes that increase the levels of complexity and uncertainty, mainly driven by decarbonisation targets on the way to achieving net zero operation and addressing climate change. As an example, towards this direction the UK government has set a bold target for zero carbon electricity by 2035. Increasing complexity comes from the introduction of a large number of converter-interfaced devices (CID) that exhibit very different dynamic behaviour, governed to a large extent by control. In addition, uncertainty in power system operation is increasing, due to the intermittent behaviour of renewable sources but also increasingly by social behaviour through EVs and potential electrification of heating as well as complex market and power industry structures. This leads to an exploding search space of possible operating conditions and contingencies, which is particularly challenging for computationally intensive stability assessment and dynamic studies. This aspect coupled with the increasing complexity of dynamic behaviour, makes identifying critical operating conditions and contingencies challenging. Consequently, these developments raise the need for improved representation and understanding of dynamic phenomena as well as fast and informative dynamic security and stability assessment. Both aspects are crucial in order to avoid potentially hidden risks of instability that in the worst-case scenario can lead to widespread events and even blackouts. Consequently, the aim of this proposal is to develop methods, tools and models needed to achieve a secure, resilient and cost-effective power system operation. Building on progress made in the initial part of the fellowship, the extension will continue focusing on two main directions. From one hand, it will develop tools, methods and models to represent and investigate the changing dynamic behaviour of power systems in order to capture new arising dynamic phenomena, spanning both transmission and distribution (e.g. offshore/onshore wind, solar PVs, HVDC links, EVs, heat pumps, electrolysers, etc.). On the other hand, it will develop novel machine learning based and data-driven methods for the fast and informative stability assessment as well as the estimation of the stability boundary. This direction will enable unique understanding of the dynamic behaviour that will lead to ancillary services and control to mitigate or alleviate the impact of disturbances and improve system security and resilience. In addition, the fellowship extension will continue and ramp-up engagement with industrial partners to capture practical aspects and fine tune developed methodologies to pave the way for real world applications. In effect, the results of the fellowship will enable more secure, resilient and potentially more cost-effective operation of power systems due to better knowledge of system stability limits. Consequently, much higher integration of renewables and new technologies with various technical and environmental benefits can be achieved in order to meet bold decarbonisation targets in a secure, resilient and cost-efficient manner.

UKRI Gateway to Research · FY 2024 · 2024-12

Neurons are extraordinary cells that face huge biological challenges, not least because most neurons last a lifetime without being replaced. Neurons extend two kinds of long, fine processes that differ in their composition and function: axons and dendrites. Axons can be a metre long in a human leg. Dendrites are much shorter but are often elaborately branched. Neurons must make the right connections with other neurons via synapses, generating thought and motion, and must also communicate with muscles. Synapses can also last a lifetime, enabling us to form memories, but are rapidly remodelled to allow us to learn. To develop and then maintain neurons over decades requires constant delivery of new material, made and packaged in the cell body then transported long distances to where it is needed. This vital traffic is carried by proteins that 'walk' along protein filaments called microtubules, acting as tiny motors. Movement away from the cell body uses kinesins, such as kinesin-1. This latter role is vital since most of our lives are spent with neurons in maintenance mode, with defects leading to neurodegenerative disease and contributing to ageing. Our aim is to investigate kinesin-1's role in the development of neurons, and how it contributes to their maintenance. We will use the nematode worm, C. elegans, which is ideal for studying neurons as they develop and function in a living animal. Complete loss of kinesin-1 is lethal, so most studies have used worms with partially functional, defective kinesin-1. These worms have never had normal kinesin-1, so if a function is affected, it could be due to an underlying developmental problem, rather than something happening now. Likewise, one cannot pinpoint precisely where in the neuron kinesin-1 works. Instead, we will use an approach where we can degrade kinesin-1 rapidly at will, simply by adding a chemical to the worms. The key novelty is the ability to remove, not just hobble, kinesin-1 on a fast timescale, in worms that have developed normally up to that point. Our objectives are: To determine how acute loss of kinesin-1 at different times in development and adulthood affects worm locomotion (crawling and swimming) To investigate how kinesin-1 works with another motor—kinesin-3—to drive the movement of a vitally important cargo: dense core vesicles. To distinguish between kinesin-1's role in neuronal development and maintenance through the life of the worm. We will look in detail at PVD neurons and at the neuronal network more generally. This work will reveal when and where kinesin-1 is needed at specific times in development and identify for the first time precisely how kinesin-1 contributes to the maintenance of neuronal structure, function, and worm locomotion. Such unrivalled detail will help reveal the full impact of kinesin-1 deficit, which occurs during neurodegeneration or ageing. This research aligns with BBSRC's goals of understanding the rules of life; generating integrated understanding of health, ageing and wellbeing; and developing a highly skilled workforce. It will use transformative technologies to generate C. elegans strains that will be a valuable resource for the C. elegans research community. Our novel method of mounting C. elegans for Lattice Lightsheet microscopy will open up this microscopy method for others. Our analysis of complex particle behaviour will provide novel functional insights that will be of importance for cell biologists, neurobiologists, biophysicists and mathematicians.