University of Manchester

UKRI Gateway to Research · FY 2026 · 2026-09

With more than 30 missions planned to take place by 2030, culminating with the return of humans to the Moon through the NASA Artemis programme, we are currently witnessing an incredibly exciting lunar exploration renaissance more than half a century after the end of the Apollo programme. Studies of samples returned by the Apollo astronauts between 1969 and 1972 have transformed our understanding of how planets form and evolve. And 50 years after these samples were returned to the Earth, we are still making crucial discoveries about the Moon, for example that volcanic rocks from the Moon contain water trapped inside tiny crystals. Yet, many fundamental questions have remained unanswered, such as how and when did the Moon form, and how did the Moon's primordial crust form. Canonical models postulate that the Moon formed as a result of a giant impact between the proto-Earth and a body called Theia. In these models, the Moon started as partially to wholly molten, a stage known as the lunar magma ocean. During cooling, dense mafic minerals crystallised first and sank to the bottom of the lunar magma ocean; Ca-rich plagioclase then formed and floated atop the lunar magma ocean after 70-80% solidification, forming a global anorthosite crust. Chronological investigations of Apollo samples from this primordial lunar crust have yielded dates clustering around 4.35 billion years - some have argued that this indicates protracted crystallisation of the lunar magma ocean over ~150 million years with a Moon formation 4.5 billion years ago, though others have suggested that the Moon was much younger and only formed shortly before 4.35 billion years ago. Thanks to detailed remote sensing investigations of the composition of the lunar surface over the past couple of decades, we now know that samples returned by the Apollo missions all originate from an anomalous region of the lunar nearside characterised by elevated abundances of some geochemical elements such as potassium (K), rare earth elements (REE), and phosphorus (P) - an area called the Procellarum KREEP Terrane. These features may have been caused by a large impact soon after the Moon’s formation, forming the putative ~3000 km diameter Procellarum basin. This Procellarum impact event could have triggered large-scale melting of the lunar nearside and resetting of chronological systems at 4.35 Ga, explaining why Apollo sample-based models could be biased towards younger Moon formation ages. To decipher when the Moon formed, we will investigate samples from outside the Procellarum area, and notably newly discovered anorthosite meteorites that likely originated from the Moon's farside. Our work will involve two complementary approaches, including (1) precisely dating the formation of these farside meteorites using the Sm-Nd and Pb isotope chronological systems, and (2) revisiting the model formation age of the Moon using the iodine-plutonium-xenon system. Our team has a strong scientific track record of tackling important lunar and planetary science questions through sample analyses, and we have pioneered the development of most of the techniques that are central to this project. We are, therefore, ideally placed to finally unravel when the Moon formed.

UKRI Gateway to Research · FY 2026 · 2026-09

The solar system formed from the collapse of a cloud of interstellar gas and dust ~4.6 billion years ago. The violent nature of planetary accretion modified the composition of the original planetary building blocks, erasing much of the record of the material that made up the early solar system. However, some primitive grains of dust and ice survived accretion and were later incorporated into primitive comets and asteroids. By Identifying and characterising the chemical composition of these primitive grains we aim to provide new insights into the chemical makeup of the interstellar material that comprised the early solar system and better reconstruct the processes that resulted in the distribution of volatile elements, including water, throughout the solar system potentially making Earth the habitable planet we know today.   Comets are balls of dust and ice that formed in the deep outer solar system. As such, they are made up of some of the most pristine material left over from the formation of our solar system. However, because comets are essentially made up of ice and loosely packed dust, they are destroyed when they enter our atmosphere. Our understanding about the composition of comets is therefore primarily from material returned from comet 81P/Wild 2 by the NASA Stardust mission, and from the ESA Rosetta mission which visited and measured the cloud of ice and dust surrounding comet 67P/Churyumov–Gerasimenko. The composition of volatile elements including oxygen and the noble gases measured within these two comets was found to be distinct from the composition of the Sun, which makes up more than 99.9% of all the matter in our solar system. Comets are therefore likely made up of material inherited from the cloud of interstellar gas and dust that existed before the formation of the solar system. Comets therefore witnessed the birth of the solar system and If only we could get our hands on cometary material, it could provide us with a record of how our solar system went from a cloud of gas and dust to the dynamic planetary system we know today.   This project will therefore measure the oxygen and noble gas composition of cometary remnants grains found within primitive meteorites. These grains potentially represent cometary material, or grains that formed through the interaction with cometary ice. By studying the proportion of different isotopes of O and noble gases we will confirm if these grains have a cometary origin and then use them to reconstruct the composition of the early solar system. Finally, by measuring grains from different meteorites that formed in different parts of the solar system, we will better understand how cometary material was distributed across the solar system and the role this material played in delivering volatiles to Earth.   We will develop new extraction techniques to measure noble gases in these small sub mm-sized grains and interface that to unique highly sensitive instruments we have previously developed. These developments will provide the best chance at measuring cometary volatiles signatures held within cometary remnant grains and ensure that the UK maintains the analytical facilities required for future sample return missions. The results of our project will provide a detailed picture of the different volatile-rich material that made up our early solar system and provide a foundation for the upcoming UK-led ESA Comet Interceptor mission planned for launch in 2029.  

UKRI Gateway to Research · FY 2026 · 2026-09

This proposal focuses on exoplanets - planets that orbit stars other than the Sun. We currently know of around 6000 such planets. The arrangements of exoplanets around their host stars and the frequency of exoplanetary systems throughout our Galaxy remain poorly understood. This is mostly because the data we have obtained so far are dominated by planetary systems occupying only the portion of our Galaxy near the solar neighbourhood. The Vision of this proposal is to seek to dramatically expand our knowledge of exoplanet systems to encompass host stars with a much wider range of age and composition. This vision requires the capability to detect exoplanets in large numbers across Galactic distances in order to access different stellar hosts. Soon after launch in October 2026, the NASA Nancy Grace Roman Space Telescope will initiate a 5-year Galactic-scale planet census of up to 200,000 exoplanets that will include planets orbiting close to their host (hot exoplanets), planets orbiting far from their host (cool exoplanets), and even planets that do not appear to orbit any star (free floating planets). This dataset will be obtained using two very different exoplanet detection methods. This proposal seeks to develop tools that can effectively combine the results of both methods. In March 2025, the ESA Euclid mission is due to image the area later to be surveyed by Roman, in a unique scientific partnership that will ultimately provide significant improvements in the quality of results Roman will deliver. Kerins, the Project Lead of this Small Award proposal, has leading roles within both the Euclid and Roman exoplanet surveys and his work has been pivotal in getting Euclid to undertake coordinated observations with Roman. Through this Small Award, Kerins requests support for his work and for a new Research and Innovation Associate to develop, test and apply tools that will form the heart of the exoplanet census studies with Euclid and Roman data. Funding from April 2026 will span the critical period from completion of the Euclid survey component to early Roman observations, including first science results from joint Euclid/Roman observations. These early results will have huge scientific impact and will capitalise on UK leadership within both missions. The science from Euclid and Roman will allow us to relate exoplanet properties to stellar host properties. It will enable us to measure more accurately the Galactic abundance of planets that could support life. It will provide much stronger and more comprehensive tests of planet formation theory. The proposed work, undertaken as a key part of the Euclid and Roman science team effort, will include: 1) the development and application of next-generation Galactic scale simulations of exoplanet detection through both transit and microlensing methods; 2) joint Euclid-Roman analyses of some of the first exoplanetary systems detected by Roman using transit and microlensing methods; 3) early identification and analyses of free-floating planet candidates detected using microlensing.

UKRI Gateway to Research · FY 2026 · 2026-09

Particle physics seeks to answer the most fundamental questions about nature. This involves identifying the basic constituents that make up our Universe and understanding their interactions. While such an aim is undoubtedly ambitious,  particle physicists have made giant strides in answering these questions. In particular we have a very successful theory known as the Standard Model which describes, to often astonishing precision, three out of the four fundamental forces in nature. Yet in spite of this great success, many profound questions still remain unanswered. This includes the observation that only five percent of the material Universe is visible matter described by the Standard Model, the remainder being the so-called dark matter and energy.  The observed excess of matter over anti-matter, which explains our physical world, is also not described by the Standard Model. Our proposed project wishes to significantly advance the understanding of such key unanswered questions. We aim to play a leading role in ongoing efforts by the  international particle physics community to better understand still murky aspects of the Standard Model and to discover new physics beyond it. We have world-leading expertise in Standard Model physics as well as in theories of physics beyond the Standard Model, which are both crucial for future discoveries. Our expertise in Quantum Chromodynamics (QCD) is critical to exploit the data from particle colliders such as the LHC. Our research is at the forefront of constructing tools known as "parton showers" which are needed to simulate the high-energy proton-proton collisions at the LHC and physics at future colliders. Our proposal addresses an urgent need to develop the accuracy of parton showers to keep up with the increasing precision of the experimental data, without which future discoveries will be severely hampered. On the other hand, work of this nature requires deep insight into QCD and presents many theoretical and computational challenges. A major part of our proposal is concerned with confronting such challenges and developing computer simulations for collider physics that offer unprecedented theoretical accuracy. We expect that the work we propose in this direction will be used by all the experimental collaborations at the LHC and future colliders, and thus have a major impact on future discoveries. Another important part of our proposal is concerned with developing theories of physics beyond the Standard Model. If Standard Model predictions are found to disagree with experiments, then we need concrete models of new physics to confront against the data and build a new theory. We have considerable expertise in physics beyond the Standard Model which we have used for the construction of compelling extensions of the Standard Model. Such work directly addresses understanding the nature of dark matter, the question of matter-antimatter asymmetry, exploring systems showing novel quantum behaviour, and the possibility of new as yet undiscovered forces in nature. Here we also propose to combine expertise in particle physics with that in cosmology, allowing us to combine interpretation of LHC data and astrophysical observations to discover answers to puzzles like dark matter. Our proposed work involves new theoretical ideas, rigorous methodology and the use of the latest and most precise experimental data from both colliders and cosmology. We thus expect that the work carried out here will strongly influence the course of future studies and shall be of lasting value to the field.                          

UKRI Gateway to Research · FY 2026 · 2026-06

Therapeutic oligonucleotides are a powerful drug modality with the potential to treat many diseases. The rapidly growing number of therapies approved and in advanced clinical trials will place unprecedented demands on our capacity to manufacture oligonucleotides at scale. Solid phase phosphoramidite chemistry has underpinned small scale DNA synthesis for decades, however this approach was not developed with large scale applications in mind and the method suffers from inherent limitations that restrict its scalability and sustainability. During Phase I of my Future Leaders Fellowship, my team developed a transformative biocatalytic approach to efficiently produce oligonucleotides in a single operation, which contrasts with the iterative rounds of chain extension, capping, oxidation and deprotection associated with established methods [Science 2023, 381, 754; Science 2024, 384, eadl4015]. Using engineered enzymes, we were also able to produce diverse oligonucleotide sequences containing a range of pharmaceutically relevant modifications [manuscript in preparation]. In Phase II of the research program, we will extend our approach to the production of real-world therapeutics with increased structural complexity. To this end, our cascade process will be adapted to produce oligonucleotides equipped with bioorthogonal reactive handles (e.g. amines, alkynes) to allow facile downstream conjugations to a variety of drug delivery vehicles, including glycans, antibodies and peptides. Such conjugations are commonly needed to ensure effective delivery of the oligonucleotide therapy to the target organ or cell. Finally, we will develop convergent oligonucleotide assembly strategies where enzymatically synthesized fragments produced in parallel are assembled using DNA ligases to produce sequences containing a greater variety of chemical modifications.

UKRI Gateway to Research · FY 2026 · 2026-06

Earth is a habitable planet as a result of its unique atmospheric composition and the presence of liquid water at its surface, both of which help regulate long term climate. The amount volatiles (e.g., H2O, O2, CO2 and Ar) is controlled by a careful balance between the amount going into the solid Earth (for example during subduction) and that coming out (for example during volcanism). The majority of outgassing is thought to occur in volcanically and tectonically active regions. However, recent work has identified that volatiles may be passively degassed in regions not directly related to volcanism. The diffuse nature of this passive outgassing makes it difficult to identify, accurately quantify and determine its extent, meaning it has not previously been fully constrained. Determining these fluxes becomes increasingly difficult when trying to measure volatiles such as carbon, which are critical to understand due to their role in climate regulation, but take part in chemical and biological reactions. Whether this hidden diffuse flux is globally significant and whether it is an important component of the global volatile cycle over geological timescales, therefore remains unknown. Groundwater is ubiquitous across the globe. Volatiles can accumulate within and interact with groundwater as they are exchanged between the deep interior and surface making it an excellent archive of these processes. Noble gases are powerful tracers of fluid provenance and physical processes as they are inert and different terrestrial reservoirs have distinct noble gas compositions. Noble gas measurements in groundwater therefore provide the ideal tool for understanding volatile fluxes from Earth’s interior to its surface. Typically helium has been used to investigate fluxes but in isolation, it cannot fully distinguish between different mantle sources. However our recent analytical advances allow for argon measurements at sufficient precision to determine excesses in groundwater and for mantle sources to be fully disentangled. We therefore plan to analyse the noble gas composition of groundwater and couple this with groundwater age constraints to better understand the role of quiescent magmatic diffusive degassing regionally and globally.  This research will shed new light on the provenance and migrationary history of magmatic volatiles within areas where there is no volcanism and evaluate how this changes spatially and temporarily across Earth to determine whether this is a globally significant flux. More specifically we address the following questions: 1) does this diffusive magmatic flux occur in different non volcanic geological settings? 2) What is the source of these fluxes and how do volatiles migrate within the aquifer? 3) how does the flux change between different non volcanic geological settings? 4) Is this globally pervasive and can this be quantified? By addressing these questions, and quantifying these new fluxes this project will provide a more detailed account of Earth’s global volatile cycle, feeding into the UN Global Carbon Project, GEO-CARBON and IPCC inventories, and help us better understand the geological processes that control volatile distribution and the long-term evolution of Earth’s surface environment.

UKRI Gateway to Research · FY 2026 · 2026-03

Groups are algebraic structures that encode symmetries of mathematical objects. These objects may be very concrete geometric shapes like polyhedra, abstract algebraic structures like rings or fields, or even physical systems. Groups are therefore of fundamental importance in many areas of mathematics and physics. Some groups are naturally represented as symmetries of a space. For instance, the symmetry group of a polyhedron consists of rotations and reflections of the Euclidean space the polyhedron lives in. But many other groups are not of this form, and the main thrust of representation theory is to describe how a given abstract group can be represented as symmetries of some vector space in terms of linear maps or matrices. This project focuses on the representation theory of finite groups on vector spaces over fields of positive characteristic, or lattices over rings closely related to the integers. This area is called the “modular representation theory of finite groups”, and it is one of the major research directions within representation theory due to the rich and difficult structure of such representations and multiple strong and well-evidenced conjectures, including Donovan’s conjecture which we will address in this project. Using the terminology of the field, the overarching aim is to understand “block algebras” and their “module categories”, which encode their representations. This project is subdivided into three work packages. In the first package we will broaden the scope and look at the modular representation theory of profinite groups – a class of topological groups closely related to finite groups. Profinite groups appear naturally in number theory, but their modular representation theory is still being developed. Moreover, there are striking structural similarities between block algebras of finite groups over p-local rings and block algebras of profinite groups. I will explore these structural similarities and develop the theory of blocks of profinite groups further. There is evidence that Donovan’s conjecture may have a much cleaner answer in the profinite setting, and exploring this idea is a main aim of this project. Profinite groups are ubiquitous across mathematics, in particular in number theory, so results on their modular representation theory will have fruitful applications elsewhere. In the second work package we will study the deformation theory of block algebras defined over a p-local ring. Deformation theory is a powerful tool in the representation theory of finite-dimensional algebras, and my own research has generalised that to the mixed-characteristic setting encountered in block algebras defined over a p-local ring. This approach has already had an impact on Donovan’s conjecture, and in this project we will develop this approach further with a view towards not just Donovan’s conjecture but also the Donald-Flanigan conjecture – the main conjecture on the deformation theory of block algebras. Both work packages above are linked to the representation theory of finite-dimensional algebras in terms of methodology and approach. The proposed work will reexamine the links between the representation theory of finite groups and finite-dimensional algebras, two areas which have diverged in the past few decades. In the third work package we will apply all of the above to make headway on a general reduction for Donovan’s conjecture in the classical finite group setting. This is very ambitious, but good progress has been made in recent years and results will have a major impact on the whole field.

UKRI Gateway to Research · FY 2026 · 2026-03

Inflammasomes are multi-molecular protein complexes that play key roles in amplifying inflammatory responses in different disease settings. For many years we have known that a cell, typically a macrophage, is able to generate a single inflammasome complex that will catalyse the unconventional secretion of interleukin-1 (IL-1) family cytokines and thus drive inflammation. However, we still have very little understanding of the cellular mechanisms that coordinate and control inflammasome formation, both in the healthy state and in disease. In this application we will explore new concepts to better understand inflammasome activation. Principally we propose that a cell coordinates inflammasome formation through the spatial remodelling of its intracellular cytoplasmic compartment leading to inflammasome formation on endolysosomal/organelle membranes. Here we propose studying the effects of diverse NLRP3-inflammasome activating stimuli on organelle position, morphology, and dynamics, and to investigate the interactome of endogenous NLRP3 that coordinates its membrane recruitment and activation in space and time. Thus, here we will examine the temporal and spatial molecular interactions that govern control of inflammasome-dependent inflammation. Importantly, we aim to translate the basic mechanistic cellular work into an in vivo context to understand mechanisms of inflammasome activation in an organism. The NLRP3 inflammasome is known to contribute to the worsening of major cardiovascular, metabolic, and neurological diseases and so our findings will be directly relevant to the therapeutic targeting of NLRP3-dependent inflammation.

UKRI Gateway to Research · FY 2026 · 2026-03

How is the universe evolving and what roles do dark matter and dark energy play? What is the nature of dark matter and dark energy? What are the fundamental particles and fields? Why is there more matter than antimatter? What is the nature of neutrinos? To answer these fundamental physics questions, the next generation flagship experiments in neutrino and dark matter will employ noble elements (argon and xenon) as active targets for particle detection. These internationally-leading experiments will rely on detection of light emitted in the vacuum ultraviolet (VUV) wavelength range. Argon and xenon scintillate in the 120-140 nm range and 165-185 range, respectively. This is a problematic region for light detection, where current photodetection technologies perform poorly. Indeed, efficient detection of light down to a single photon using optoelectronic devices is a key theme in the UK’s Quantum Strategy, and extending the detectable spectral range is an established goal of quantum imaging research. We target this extension to VUV, where the decreasing wavelength poses challenges for detection due to the rapid increase of the reflectivity. The state of the art in large-area silicon sensor array technology is Silicon Photomultipliers (SiPMs) with unsatisfactory performances of photon detection efficiency between 15% (Hamamatsu, at 178 nm) and 22% (FBK Low Field UV optimized), dropping to 10% for 128 nm. With this project, we aim at boosting the quantum efficiency and collected number of photons for VUV sensitive photon sensors via a strategy that combines smart sensor designs, the use of 2D materials, and the application of novel readouts. This will unlock the potential of a wide range of tonne- and kilotonne-scale neutrino and dark matter experiments such as DUNE, NEXT, DarkSide, LZ and nEXO. These experiments will need to instrument large readout areas (10–100 m2) both at room temperature (DUNE near detector and NEXT experiments) and in cryogenic conditions (DUNE far detectors, DarkSide, LZ and nEXO experiments).  The technologies pursued aim to reach at least a factor of two improvement in the VUV wavelength range relevant for noble elements, whilst preserving comparable cost per unit area and timing performance. Our strategy is to develop high-efficiency single photon sensitive devices using novel graphene coatings on silicon and selenium, and metaoptics. Our R&D program comprises the development of three distinct lines of technology and their integration into detectors: SiPMs with increased VUV detection efficiency  (WP1), amorphous selenium sensors (WP2), and metaoptics devices (WP3). While the three technologies are distincts, they are highly complementary and can be combined for further improvements. We also propose a common testing strategy (WP4) to characterise the relative noise and quantum efficiency of the sensors in the VUV, and will assess the benefits of merging metaoptics and the novel photosensors. Such a common strategy will optimise not only the performances of each design, but will also allow us to abate the testing cost and lab time. This program leverages capability and infrastructure across a range of UK institutes for the DUNE and DarkSide programmes.

UKRI Gateway to Research · FY 2026 · 2026-03

We will create a Hub of excellence in Arts and Humanities Doctoral training in the North of England. Bringing together the collective strengths of 10 successful HEIs, the Hub puts quality, inclusivity, and student voice at the centre of its training and development offer. The developmental opportunities we provide allow our students to excel and think in new and innovative ways about how their research may be communicated, created, articulated, responded to and used. Our emphasis on outreach and widening participation emphasises the democratising of research, creative, and academic practices. We embed EDI, student voice, and shared decision-making in a responsive and efficient Hub. Our planned activities provide opportunities for student involvement and leadership. We engage our cohort in various ways to recognise different learning, working patterns, and skills needs. We envisage a set of projects and initiatives that mean the Hub is the most inclusive space for PG work in the UK. We look to embed EDI, sustainability and wellbeing in every activity, thereby equipping a new generation of students with the skills to be inclusive, attentive, ethical research leaders.

UKRI Gateway to Research · FY 2026 · 2026-03

Context and challenge: The neural tube is the precursor to the brain and spinal cord. Congenital neural tube defects are prevalent in humans (>1/1000 births). Designing prevention strategies is complicated by the many different mechanisms that must occur at a subcellular level to control this tissue-scale event. Adding to this complexity, the neural tube forms via different mechanisms along its length. For example, most of the human neural tube forms via folding a sheet of cells and subsequent inflation (primary neurulation). One important subcellular mechanism behind this process is mechanical contractility at the belt of cell-cell junctions that connect cells. This bends the tissue into shape. Contractility is driven by a protein complex called actomyosin. However, the base of the spinal neural tube forms via inflation of a fluid-filled cavity within an initially solid tissue, from the inside out (hollowing neurulation). Although this mechanism of cavity inflation has relevance to the development of many structures (kidney, gut, early embryo cavities), the complex interrelationship between cell mechanics and chemical signalling has prevented a full understanding of the cell biology behind this process. Using zebrafish embryos as a tractable model of hollowing neurulation, we recently discovered that actomyosin contractility is required for neural tube inflation. However, instead of acting at cell-cell junctions (as in primary neurulation), actomyosin is active at the base of small structures called primary cilia, where it appears to modulate their function. Acting like ‘antennae’ for the cell, cilia project into the fluid-filled cavity and integrate chemical and mechanical information, translating this into signals within the cell. Interestingly, we found that both zebrafish with defective cilia and zebrafish with defective actomyosin contractility had similar inflation defects. Together, this suggests that actomyosin is playing a role in regulating the pressure within the inflating neural tube, via a role in cilium function. Aims: We aim to uncover the mechanisms linking cell mechanics and cell signalling during inflation of the vertebrate neural tube. Objectives: To unpick the interrelationship between actomyosin contractility, cilium signalling and lumen inflation, we propose an optogenetic approach developed in the lab, which will allow us to specifically manipulate actomyosin contractility at cilia in response to light. We will also use light-activated approaches to manipulate cilia signalling with precise temporal control and will modulate the pressure within the neural tube cavity via microinjection. Using fluorescently labelled sensors for cilia and for organ structure and signalling components, we will carry out high resolution imaging within live embryos. This will allow us to assess the effects of these manipulations from the subcellular to the tissue scale in real time. Using this approach, we will determine how A) actomyosin regulates cilium structure and function, B) ciliary signalling regulates tube inflation, C) cilia transduce mechanical signals. Applications and benefits: Together, this research will 1) further understanding of how early organs form, 2) uncover links between cell mechanics, cell signalling and the shaping of animals, 3) uncover new roles for actomyosin and cilia in cell biology and signalling. These applications and benefits have relevance to both animal development and disease. Relevance to BBSRC: As well as furthering our understanding of the important and disease-relevant developmental process of neurulation (BBSRC objective 3.2 ‘understanding the rules of life’), this proposal will further develop cutting-edge optogenetic approaches within a live vertebrate (BBSRC objective 5.1 transformative technologies).

UKRI Gateway to Research · FY 2026 · 2026-03

This proposal investigates fundamental robust feedback control theory of nonlinear dynamical systems via input-output methods. The input-output approach in control theory describes dynamical systems as operators mapping an input to an output. Feedback stability in this input-output framework means that endogenous signals around the feedback loop are well-behaved for all exogenous inputs – in an input space – injected into the feedback loop. Influential input-output feedback stability results which can be applied to nonlinear systems to guarantee robust feedback stability include the classical small-gain, input-output passivity, input-output dissipativity, and absolute stability criteria, as well as more modern input-output stability approaches such as the Integral Quadratic Constraint framework and dynamic dissipativity. However, all these important methods guarantee feedback stability for all exogenous inputs within a specified input space. If a closed-loop system is well behaved for a subset of inputs within an input space, but not well-behaved for every input in that space, these methods cannot guarantee closed-loop stability in this scenario. However, no feedback system will ever encounter every possible exogenous input. In fact, in many applications, some basic prior information is known about the exogenous inputs, such as the maximum energy or the maximum magnitude of the possible input excitations, that the feedback loop will encounter. If a controller can be designed to guarantee feedback stability only for the exogenous inputs a feedback loop is expected to experience, instead of guaranteeing feedback stability for all possible inputs, this controller would be less conservative and therefore can provide high levels of closed-loop performance as a trade-off for this reduced conservatism in stability. It is therefore the aim of the proposed research to develop theory which can guarantee stability of a closed-loop nonlinear dynamical system for a restricted subset of exogenous inputs, even if such a system would be destabilised when subjected to inputs outside of this restricted subset. We call this type of stability ‘input-restricted stability’. Using graph-separation techniques, we intend to show how restricting the exogenous inputs of a feedback system restricts the regions of the system graphs which we are interested in, such that only separation of the restricted graphs is required to prove input-restricted stability. Once such theory has been established, we aim to develop input-restricted feedback stability synthesis theory to enable the design of controllers which achieve a certain specified level of input-restricted stability. Such controllers would enable an engineer to guarantee input-restricted stability for a given norm restriction on the exogenous inputs, such as the maximum energy or maximum magnitude of external disturbance/noise excitations, thereby allowing greater freedom in controller design compared to standard controller synthesis methods. This then leads to higher levels of closed-loop performance in exchange for reduced conservatism in stability. After developing the input-restricted stability theory and input-restricted controller synthesis methods, we shall develop both simulation and hardware experiments to demonstrate the power of these new methods. These examples will be physically motivated and designed to showcase the applicability of input-restricted feedback stability control theory.

UKRI Gateway to Research · FY 2026 · 2026-03

Authoritarianism is rising globally. According to the latest V-Dem Institute Democracy Report, the democratic gains made over the past 30 years have been eroded, with 71% of the world’s population now living in autocracies, an increase from 48% in 2013. Many former liberal democracies (such as Hungary, India, Tanzania, and Turkey) have elected populist, right-wing governments that have undermined civil and political rights, such as by weakening judicial independence and violating LGTBQIA+ rights. At the same time, authoritarian powers that reject liberal democratic values have been rising in influence. Rising global authoritarianism also has a transnational element, with authoritarian actors working together in transnational partnerships, including partnerships between political leaders (such as between Viktor Orbán, Donald Trump, and Marine Le Pen) and international gatherings of conservative and far-right actors (such as at the Conservative Political Action Conference (CPAC)). What should be done in response? Although recent work in political philosophy has considered how to counteract authoritarian practices domestically, on how to frustrate and block authoritarian movements within your own state, political philosophers have not addressed the justifiability of potential responses to rising global authoritarianism, tackling democratic backsliding and authoritarian shifts in other states and challenging the rising influence of authoritarian actors globally. Our project will therefore help to understand much more fully the ethics of the potential responses to rising global authoritarianism by liberal actors, including individuals, civil society actors, liberal democratic states (both in the Global South and the West), and regional and international institutions. It will offer a two-level analysis of both more ideal responses and nonideal responses relevant for an even more problematic global order. The responses range from developing new forms of international leverage and increasing military capabilities, to using means such as cyber-attacks and coercive economic responses that could potentially compromise liberal values. Each form of response raises vexing ethical issues that will be the focus of the project, including the following: Should liberal actors use means of ‘militant democracy’ applied internationally to respond to global authoritarianism, even if this will undermine ideals of liberal integrity? Should military spending be increased to tackle threats to liberal states? Which liberal actors (e.g. liberal governments, civil society organisations, political parties, and individuals) have rights and potentially weighty duties to respond to rising global authoritarianism? Should tackling global authoritarianism be prioritised over other goals, such as responding to global poverty and climate change? The project team will comprise Pattison (PL) and Hjorthen (PcL). It will contribute to the fields of political philosophy and International Relations on how to respond to rising authoritarianism and aim to assist practitioners in their efforts to respond to authoritarians. The project will lead to a jointly authored monograph and two academic papers, as well as a policy brief, a podcast series, a series of short videos (distributed via Tik Tok and YouTube Shorts), and a policy-focused workshop aimed at influencing policymakers.

UKRI Gateway to Research · FY 2026 · 2026-03

Interactions between waves and vortices play a crucial role in a vast range of physical scenarios, ranging from atmospheric fluid flows to superconductors. In superfluids, vortices can arise as discrete, indivisible units with quantised circulation, giving rise to many celebrated quantum fluid phenomena e.g. topological phase transitions and quantum turbulence. However, the detailed dynamics of vortices is less well understood in quantum fluids with a free surface - i.e. a liquid interface like the one commonly seen between air and water - which is a prominent feature of strongly interacting quantum systems like liquid helium. This project will develop a microscopic theory of quantum vortices in the presence of a free surface, focussing in particular on their interaction with surface waves. Our theory will elucidate the fascinating stability properties of these systems observed in recent UK experiments, and find ways of using the free surface to control vortex dynamics. Advancements in understanding these strongly interacting quantum systems could have applications in emerging technologies, which can drive innovation and economic impact. Alongside the scientific objectives, the project will leverage its ties to the UK quantum community to produce a series of short films about the National Quantum Technologies Programme (NQTP) - increasing public awareness of this important investment. These films will be displayed as part of an Art-Science exhibition (2025) in collaboration with researchers at the University of Nottingham, culminating in a mini-documentary sharing some of the most important success stories of NQTP. The filming process will be further used as an opportunity to engage with junior researchers in the UK community, providing them with an online platform to share their research with a broader audience. In doing so, the ambition of the project is to identify the next generation of outreach talents, with the long-term goal of making cutting-edge research more accessible and raising science literacy in the general population.

UKRI Gateway to Research · FY 2026 · 2026-03

Osteoarthritis is the most common arthritis, and a leading cause of disability globally. This debilitating disease is characterised by the breakdown of cartilage in synovial joints. In a healthy joint, cartilage is a smooth tissue that covers the ends of the bones, allowing friction free movement. Cartilage is a dense matrix consisting of large collagen fibres produced by a specialised cell type, chondrocytes. Collagens are a vital component of cartilage, providing structural integrity to the tissue and allowing it to withstand mechanical load. In osteoarthritis, the matrix irreversibly degenerates, leading to chronic pain and stiffness in the affected joints, co-morbidities, disability, and premature death. In the UK alone, 10 million adults suffer with osteoarthritis, yet treatments are limited to pain relief, physiotherapy, and joint replacement surgery (arthroplasty), which is expensive and risk-laden, with variable success rates.   Our recent studies of human DNA and patient cells has identified that a subset of adults who are at higher genetic risk of developing osteoarthritis produce greater amounts of COLGALT2, specifically in chondrocytes. COLGALT2 is an enzyme capable of glycosylating collagens, a process of transferring sugars to the protein surface. This is essential for collagen structure and function. We have further identified that these elevated levels are present from the beginning of life (during development of the skeleton), indicating individuals are “pre-programmed” to develop osteoarthritis, ostensibly due to conferred weaknesses to the cartilage. To date, this enzyme remains largely uncharacterised, and its biological role in joint disease is unknown.   This proposed research will utilise three interlinked yet independent innovative approaches to understand the biology of COLGALT2 in cartilage and how this contributes to osteoarthritis pathogenesis. We will primarily answer three key questions: Do COLGALT2 levels in mature chondrocytes directly impact collagen glycosylation, impacting fibril assembly and stability, contributing to disease?  Do COLGALT2 levels impact the development of the joint, shape or tissue composition, predisposing individuals to disease? Can drug repurposing allow us to modulate COLGALT2 in chondrocytes and be applied as a health intervention?     In Newcastle, we will first culture human primary chondrocytes, isolated from osteoarthritis samples post-arthroplasty. Applying established molecular technologies, we will modulate COLGALT2 levels and quantify the impact upon both the chondrocyte proteome and the matrix composition using a range of cell biology and 3D culture methods. To ensure the success of this work, we will draw upon the vast expertise of our global network of leading scientific collaborators. In Bristol, we will use in vivo technologies to complement and validate these findings in zebrafish. Zebrafish provide an excellent model of the skeletal system. Many skeletal structures are shared with humans and can be easily visualised in the translucent fish. This is enhanced by our ability to fluorescently label specific musculoskeletal cell types. Finally, we will conduct a high-throughput screen of approved drugs to identify pharmacological modulators of COLGALT2. We will then transfer this knowledge to the Newcastle and Bristol laboratories, to validate the results in our optimised in vitro and in vivo models, respectively.   Understanding the fundamental biology underlying disease will bridge the gap between genetic studies and targeted therapies for osteoarthritis patients. This research has the potential to benefit millions of adults in the UK. The development of drug treatments for osteoarthritis would confer a long-term benefit at both an individual and societal level.

UKRI Gateway to Research · FY 2026 · 2026-02

Small molecule drugs continue to play a central role in the progress of medicine, accessing target space and opening up new modes of action that are inaccessible to other drug modalities. However, over the last decade, it has been widely recognised that compound libraries and lead compounds have become increasingly populated with flat and heteroatom-rich functional groups that are far removed from those present in natural products and biomolecules, instead, tending to mirror advances in contemporary synthetic chemistry. While these have undoubtedly led to the development of countless pharmaceutical products, many argue that these gaps in molecular architecture have limited biological coverage. As such, efforts are currently underway to include more three-dimensionality, bioavailability, and metabolite-likeness in emerging candidates. Nowhere is this paucity more acutely demonstrated than in the prevalence of oxygen-based functional groups such as alcohols and carbonyls in small-molecule therapeutics. Therefore, the development of new late-stage oxygen-atom insertion methodologies that are simple, general, and robustly applicable to the synthetic demands required in drug discovery pipelines is crucial. To meet this challenge, this proposal will introduce a novel strategy for the metal-free insertion of oxygen atoms into unsaturated carbon frameworks, termed PhotoOxyEdit. This approach seeks to leverage a widely underutilised reactive intermediate – monoatomic oxygen (oxene) – to generate valuable biradical intermediates. We propose that these seldom-encountered species can act as linchpins for the synthesis of complex oxygen-containing molecular architectures. Such intermediates have historically proven challenging to access due to the lack of practical methods for oxene generation. To overcome this, we have designed a new platform that employs violet light and the ubiquitous two-electron oxidant periodate. Through a process of targeted photoactivation, we can unlock a previously elusive pathway to selectively generate oxene under mild conditions. This approach will not only convert abundant unsaturated carbon feedstocks into value-added oxygenated fragments but also permit late-stage oxygen-atom insertion and editing within complex molecules and the potential repurposing of failed clinical candidates. Preliminary work in the group has established the successful implementation of our periodate photoactivation platform resulting in the oxene-mediated epoxidation of olefins. In addition, we have demonstrated the successful oxidative cleavage of olefins to carbonyl compounds; current methods rely heavily on the use of explosive gases and toxic transition metals. Capitalizing on these results, we propose to expand our photo-mediated oxygen editing approach towards the preparation of novel oxy-heterocyclic molecules via unprecedented oxygen-based cycloadditions, strain-release oxy-annulation, and oxidative skeletal modification. We further seek to explore the activation of strained C–C bonds to generate previously elusive oxygenated aryl bioisosteres. We finally propose to use our experience in photogenerated reactive intermediates to expand the toolkit of low-valent atom insertion chemistry to other chalcogens, including sulfur. This program is set to provide a new blueprint for the synthesis of oxygenated molecules using a novel and operationally straightforward platform centred on the targeted photoactivation of periodate. By allowing facile access to underutilised biradical intermediates, we will develop a range of new C–O and C–S bond-forming reactions from readily available feedstocks. Our research will contribute towards the UK pharmaceutical, agrochemical, and fine-chemical sectors by overcoming bottlenecks in organic synthesis and repurposing existing function-orientated molecules.

UKRI Gateway to Research · FY 2026 · 2026-02

Interactions between biomolecules sustain life as we know it. Accordingly, the spatiotemporal coordination of biomolecular interactions is critical to all biological processes. Methods to precisely measure biomolecular interactions are thus critical to the entirety of all biological research. Historically, biomolecular interactions have been studied by isolating molecules of interest and looking at what else was present. In the ‘omics-era’ of modern biology, this could be scaled up and combined with unbiased screening platforms to profile the interaction networks of isolated biomolecules at high throughput. These approaches, however, struggle to identify interactions that are either transient or labile (i.e. destroyed upon preparation of the sample). Proximity labelling technologies offer a solution by labelling nearby ‘interactors’ that can be detected in downstream analyses. Most rely on enzymes that convert inert small molecule probes into free radical intermediates that, via diffusion, bind promiscuously to nearby biomolecules. The probes contain a conjugation handle that can be used for identification, for example, biotin, which enables enrichment with streptavidin. These technologies have facilitated discoveries in various aspects of cell biology but suffer from poor resolution, labelling molecules over hundreds of nanometres. This prevents such technologies identifying bona fide interactors. The nature of the reactive intermediate dictates both the spatial resolution of proximity labelling and the types of biomolecules that are labelled. Recent advances employ photocatalytic approaches to generate localised carbene intermediates with extremely short half-lives, transforming labelling by bringing it within nanoscale proximities (~4 nm) enabling the precise identification of interactors. This ‘super-resolution’ approach, termed µMap, has defined targets of immunotherapies and small molecule-protein interactions with unparalleled precision. Although these technologies have transformed proximity proteomics, they do not efficiently label other biomolecules, such as nucleotides. Moreover, current nucleotide proximity labelling technologies also suffer from poor labelling efficiency, requiring large amounts of starting material. Nucleic acid (DNA and RNA) interactions are as ubiquitous in biology as protein-protein interactions and improvements to technologies that enable efficient and precise nucleotide proximity labelling would be of great importance, value, and interest. Here, we will develop a novel nucleotide labelling technology based on the photocatalytic generation of new nucleotide-targeting reactive intermediates that can label DNA and RNA at nanoscale distances. We will design and examine a range of precursor molecules that can be activated by a photocatalyst, adapting µMap technology for nucleotide labelling. We will undertake the development of both the photocatalyst and nucleotide-targeting probes, optimising their nucleotide proximity labelling potential. We will test our technology in vitro on synthetic DNA and RNA constructs, allowing us to establish both the efficiency and resolution of our labelling technology. We will then showcase its nanoscopic labelling potential in cells by demonstrating DNA/RNA labelling compared to the current state-of-the-art approaches. Our technology could provide 100-fold greater precision than current nucleotide proximity labelling approaches. Our technology will also be modular, so that it can be used for numerous downstream applications. Consequently, our technology could i) enable precise, efficient and sensitive nucleotide labelling to generate super-resolved nucleotide interaction maps, ii) enable precise nucleotide labelling for high-resolution imaging (electron or light microscopy; in both fixed or live cells), iii) enable the first spatially restricted labelling of nucleotides (due to reactive intermediate generation being dependent on targeted blue light irradiation), and iv) enable simultaneous super-resolution protein and nucleotide proximity labelling, in combination with µMap.

UKRI Gateway to Research · FY 2026 · 2026-02

This project seeks to understand and reduce a common and potentially dangerous type of error, where a person fails to respond to something that is right in front of them. These "Look but fail to see" (LBFTS) errors can be something trivial, like a typo in an email, or something much more significant, like a pedestrian in the street. To qualify as an LBFTS error, the item that is missed must be clearly visible and the observer must be "expert" enough to identify the item. Thus, for example, no one would be expected to find a typo in a letter that was written in a language they do not know. Collaborating researchers in the US and the UK will create object and scene databases using real-world stimuli for use in LBFTS experiments. The goal is to identify strategies that reduce these errors, so that they can be minimized in many arenas. Of particular interest are those arenas that impact national health and security, as when a radiologist fails to see signs of cancer in a lung x-ray or a screener fails to see a weapon in carry-on luggage at the airport. The creation of carefully curated object and scene databases will benefit many. Existing object databases are aging and often include objects that observers may not easily recognize (e.g., a dial-up modem). The experiments will identify objects that are correctly recognized by observers over 90% of the time. They will also quantify the memorability of each object and scene. Stimuli will be validated by replicating previous LBFTS experiments and the relative contributions of recognizability and memorability will be assessed. The resulting pattern of LBFTS errors with real-world stimuli should inform the types of interventions that are more likely to improve performance. For example, random errors are minimized when two sets of eyes look at a stimulus. LBFTS errors can provide information to improve artificial intelligence systems, so that AI might provide one of those sets of eyes.

UKRI Gateway to Research · FY 2026 · 2026-02

Austerity and Altered Life-Courses (AALC) is a major research programme exploring in detail how austerity policies across Europe since the global economic crisis of 2008-2010 have led to 'socio-political ruptures' in young people's life-courses. Austerity-driven policy agendas continue to dominate across Europe, with limited direct policy reversal and reinvestment to date. Austerity’s impacts thus remain ever-present, stretching further into the life-courses and futures of young people who have lived their formative adult years in austerity, and manifest differently according to local and national contexts. Altered lives and futures under austerity thus constitute a form of significant and long-term intergenerational inequality across Europe. This renewal project builds on the successes of the first phase of AALC, which generated over 100 young people’s unique stories of lives and futures of austerity from across the autonomous/devolved regions of Greater Manchester, Sardinia and Barcelona. Our findings and partnerships led to major conceptual and methodological developments in life-course approaches, impactful place-based community co-creation projects and future-proofing policy co-production, facilitated by PI Hall’s distinctive feminist, solidaristic leadership.   Advancing this work, the renewal project is framed around a refreshed focus on co-creating space, stories and solidarities, aiming to reframe and redress socio-economic inequalities resulting from austerity across Europe in theory, method and praxis. The research objectives are as follows: ROi. Gather and share stories of socio-economic inequalities under austerity across Europe; ROii. Co-create new spaces at multiple scales and sectors to leverage socio-economic change; ROiii. Build solidarities across and between academic and community researchers.   To meet these aims and objectives, the renewal is arranged into four main work-packages. Generating empirically informed and groundbreaking conceptual innovations, expansion of the research sites will enhance understanding of austerity futures across Northern European city regions, to include Dublin County, Ireland and Rotterdam Municipality, the Netherlands, whilst also continuing with research in the three original sites. These two new sites contribute a further empirical layer with a focus on youth migration and housing in the context of austerity, which is a growing and timely issue in these locations and within the field of austerity inequalities research more broadly (WP2). Methodological innovations are likewise anticipated, enhancing our novel Oral Histories and Futures approach to include return interviewing and group-based discussions. Collating insightful future-facing narratives from these novel life-course techniques will contribute to building a unique, cutting-edge longitudinal dataset on young people’s futures in austerity across Europe (WP1). Drawing on our original research insights, and collaborating with creative professionals and community researchers, we will also co-create a range of creative interventions (play, art piece, community podcast, and zine archive) by using storytelling as a powerful technique to engender policy and social change. These creative interventions also support our ongoing innovations in co-creating future-proofing policy praxis at local, regional and national scales (WP3). Finally, the renewal will build radical local and international solidarity research networks via the Bread and Roses collective and the CARE network, respectively, to address the inequalities generated by austerity’s lives and futures (WP4).    

UKRI Gateway to Research · FY 2026 · 2026-01

Advanced super-resolution imaging systems are crucial for driving discovery in bioscience by enabling real-time, high-resolution observation of dynamic cellular processes. The current imaging systems at the University of Manchester (UoM) do not meet our experimental needs for fast, live-cell, 3D super-resolution imaging of multiple fluorescently-labelled proteins and consequently compromises must be made between speed, resolution, and sensitivity. After extensive evaluation and testing, the Zeiss Elyra7 structured illumination microscopy (SIM) system has been selected for its exceptional performance in live-cell super-resolution imaging. This system provides super-resolution imaging at high speed, allowing 3D optical sectioning in live tissues, and the ability to image multiple fluorophores simultaneously. The camera sensitivity and low laser powers minimise photo-damage, making it possible to observe live samples over extended periods without compromising their viability. Our planned additions of laser manipulation (including optogenetics) and microfluidics drug delivery systems will further enhance its capabilities, allowing biological processes to be perturbed and simultaneously imaged at high speed and resolution. The Elyra7’s powerful image processing capabilities will allow researchers to analyse large datasets efficiently, extracting meaningful information from complex data. UoM’s commitment to open data sharing ensures that the findings and data generated using the Elyra7 will be accessible to the broader scientific community, promoting transparency and collaboration. The equipment will be housed in a purpose-built imaging suite and embedded into the UoM Bioimaging Core Facility, which is accessible to all UoM researchers and external users. The Bioimaging Facility employs 5 full-time, experienced Research Technical Professionals (RTPs) who will ensure the system is well maintained and will provide extensive user training to ensure that its full capabilities are utilised. The Facility’s commitment to inclusivity and sustainability ensures that the system will be accessible to a diverse group of researchers, maximising its impact on the scientific community while minimising its detrimental effects on the environment. The Bioimaging Facility is managed by a senior RTP, Peter March, who is Project Lead (PL) on this application, and supported by academic-lead, Sarah Woolner, a Project Co-lead (PcL) on this project. We have assembled an additional team of 15 research-leads from a range of disciplines including cell biology, cancer research, immunology, mechanobiology, matrix biology, and regenerative medicine, who all use live-cell imaging for their research and will provide an immediate skilled userbase for the system. The acquisition of the Zeiss Elyra7 live-cell super-resolution system will provide a step-change for their imaging capabilities and lead to new discoveries currently “hidden” in low resolution images. This will be particularly important for the 6 early career researchers included as PcLs on this application. These are researchers in their first independent academic position for whom access to cutting-edge tools, such as the Elyra7, is particularly crucial to advance their research and accelerate their careers. In summary, the proposed live-cell super-resolution imaging system will enable UoM researchers to observe, and manipulate, cellular processes in incredible detail, leading to new discoveries across the biosciences.

UKRI Gateway to Research · FY 2026 · 2026-01

Molecularly imprinted polymers (MIPs) are synthetic materials engineered to mimic natural recognition processes, offering high selectivity and affinity for target molecules. NanoMIPs, the nanoscale version of MIPs, have shown great promise in fields such as diagnostics, drug delivery, and environmental monitoring. However, a major challenge remains in the detailed characterisation of nanoMIPs, particularly in understanding their structure, heterogeneity, and interactions with biological targets like proteins or extracellular vesicles (EVs). Current techniques, such as dynamic light scattering (DLS) or transmission electron microscopy (TEM), provide limited insight, often lacking the resolution and detail needed for complex, polydisperse systems. This project aims to address this gap by developing asymmetric flow field-flow fractionation (AF4) as a powerful platform for studying nanoMIPs. AF4 is a versatile separation technique that provides high-resolution fractionation of particles based on size and shape making it well-suited for the analysis of sensitive materials like nanoMIPs. Our project seeks to unlock the potential of AF4 for high-resolution characterisation of nanoMIPs, providing new tools to study their structure and molecular recognition properties in unprecedented detail. This project will bring together experts from the University of Manchester and the University of Sheffield, combining complementary strengths. McDonald’s group at Manchester specialises in AF4 and nanoparticle characterisation, while Turner’s team at Sheffield is a leader in MIP design and synthesis. Together, they will leverage cutting-edge AF4 instrumentation at the Henry Royce Institute and collaborate with PostNova, an industry leader in AF4 technology, to ensure the development of protocols that are both scientifically rigorous and commercially viable. The characterisation and understanding of nanoMIPs remain limited by current analytical techniques, which struggle to resolve the complex structures and heterogeneous nature of these materials. This project seeks to overcome these limitations by developing AF4 into a robust platform capable of separating and analysing nanoMIPs at high resolution. Moreover, the project will explore the interactions between nanoMIPs and biological targets, which is crucial for applications in fields like biosensing and targeted drug delivery. Aims and Objectives: This project will develop AF4 as a routine analytical tool for nanoMIP characterisation. The specific objectives are: Design and optimise methods for the AF4 platform to provide high-resolution separation and analysis of MIP nanoparticles. Validate the AF4 platform by comparing it with existing analytical techniques demonstrating its capabilities, and limitations. Characterise the size, shape, and molecular recognition properties of nanoMIPs using AF4 when interacting with either a free protein, or surface-bound protein (EV model). Explore the relationship between nanoMIP synthesis parameters and their ability to be studied via the AF4 technique. The successful development of AF4 as a platform for nanoMIP characterization will have wide-reaching impacts across several fields. In diagnostics, nanoMIPs could be used as robust alternatives to antibodies, leading to more stable and durable biosensors. In drug delivery, understanding nanoMIP-target interactions will enable the design of more selective drug carriers, improving therapeutic outcomes. The ability to precisely characterise nanoMIPs will also be critical in environmental monitoring, where these materials could be used for detecting pollutants or toxins with high specificity. Overall, this project will establish AF4 as an essential tool for nanomaterials research, supporting the commercialisation of nanoMIPs.

UKRI Gateway to Research · FY 2026 · 2026-01

Cell function is profoundly influenced by the physical environment of the body. Changes in the stiffness of tissue environments are vital for organs to grow and wounds to heal. Cells detect and respond to such changes to adapt to mechanical strain, maintain tissue structure and coordinate cell movement. To do this, cells use their cytoskeleton to transmit mechanical force rapidly from their surroundings, via adhesion proteins at the cell surface, to the nucleus. At the nucleus, force is then converted to biochemical signals that trigger alterations in nuclear shape and rearrangements of DNA. These signals regulate processes that are fundamental to tissue growth and development, including cell movement and gene expression. Abnormal nuclear shape and altered mechanical properties are hallmarks of ageing and various diseases, highlighting the importance of understanding the processes underlying how cells respond to tissue stiffness. Remarkably little is known about how force actually leads to the precise gene expression changes required for cells to respond to their physical environment. A key challenge is the lack of detailed understanding of the molecular events that regulate this process at the nucleus. I will address this fundamental question by building on my recent unexpected discovery that some adhesion proteins, usually found near the cell surface, can locate in and around the nucleus to regulate gene expression. The surface of the nucleus is an essential interface point for registering force within the cell, so my aim is to investigate the role of adhesion proteins at the surface of the nucleus, and how they connect the cytoskeleton to the nucleus to regulate nuclear functions. I will focus on an adhesion protein called Mena, which is important for controlling how the cytoskeleton forms in cells. I found that Mena locates on the nuclear surface, where I predict it has a key role in regulating the linkage of the cytoskeleton to the nucleus. My objectives are: To establish how Mena regulates the cytoskeleton-to-nucleus connection to allow cells to respond to different physical factors, such as stiff surroundings and confined spaces, which can be encountered in different tissue environments. To determine how the association of Mena with the surface of the nucleus, and its connection to the cytoskeleton, alters DNA organisation to regulate the activity of genes. To identify how force influences a broader collection of cytoskeleton-associated adhesion proteins at the nuclear surface, and how they work with Mena to generate signals that control gene expression. This work will reveal how cells use adhesion proteins to regulate the transmission of force into the nucleus. This will impact our understanding of how fundamental nuclear functions are controlled as cells respond to the stiffness of their surroundings, and it will provide insight into the regulation of genes in tissue homeostasis, regeneration and therefore ageing. This research complements BBSRC’s mission to understand the rules of life, and closely aligns with its investment in bioscience for an integrated understanding of health. It will use sophisticated technologies to generate comprehensive maps of DNA function, and the molecular events that control this, that will be a valuable resource for the adhesion biology and gene regulation research communities. Importantly, the integration of these technologies with functional cell biology will build strategic skills capacity in data science and bioinformatics, UKRI priority areas, contributing to the development of a highly skilled workforce.  

UKRI Gateway to Research · FY 2026 · 2026-01

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 2026 · 2026-01

Failure of proteins to adopt an appropriately folded conformation is a prevalent cause of human disease and hinders the biotechnological production of valuable proteins. Misfolded proteins usually either refold to their functional states or are degraded by quality control mechanisms. When misfolded proteins evade quality control, they form aggregates that have been viewed as a hallmark of proteostasis. For instance, the organized sequestration of misfolded proteins to defined inclusion sites is a regulated process that depends on dedicated molecular chaperones, termed sequestrases. Appropriate sequestration of protein in aggregates is a defence strategy that prevents the potential dysfunction and toxicity associated with protein misfolding diseases. Although aggregation is a well-studied phenomenon and many key players are known, it remains unclear how changes in cellular states including stress, quiescence, or nutritional alterations cause protein aggregation, and the degree of stress specificity in the chaperone response to aggregate formation is unknown. Sequestrase chaperones help cells to cope with accumulating misfolded protein by sequestering proteins away from their normal productive pathways to protect against cytotoxic effects and facilitate targeted degradation. More recently, chaperone-mediated sequestration has also been identified as a regulatory response that compartmentalises key signalling molecules. For example, sequestration can act to separate signalling molecules away from their substrates and inhibitors under stress conditions. This current proposal builds upon our recent studies where we show that chaperone-mediated sequestration provides a non-canonical mechanism to fine-tune protein kinase A (PKA) signalling in yeast. We have identified a PKA inactivation mechanism based on sequestration of a specific PKA isoform. Sequestration is controlled by the Hsp42 sequestrase and is reversible such that PKA activity is restored following stress recovery. These studies reveal a previously unknown mechanism that regulates a conserved cellular signalling pathway and provides a new rationale for protein aggregation upon stress. This proposal addresses fundamental questions concerning sequestration as a protein quality control (PQC) mechanism in eukaryotic cells including: 1) How do sequestrase chaperones mediate the spatial sequestration of proteins as a stress defence strategy? The overall aim is to provide a mechanistic understanding of protein sequestration and the stress specificity of sequestrase chaperones. 2) How and why do cells sequester misfolded proteins into aggregates? As a part of this project, we aim to define rules and principles governing the formation and resolution of aggregates, which can then be exploited to design strategies to mitigate aggregate toxicity. 3) How does sequestration act as a reversible response to control enzyme activity and key signalling pathways during stress exposure and recovery. This research will provide a greater understanding of how protein aggregates form in cells and the rules determining this will address the BBSRC strategic objective: Understanding the rules of life. Beneficiaries will include researchers in the immediate 'protein homeostasis' and 'chaperone biology' communities, as well as scientists broadly interested in protein misfolding and stress. The use of yeast biochemical and genetic techniques has in the past served as a paradigm for the study of protein misfolding across all eukaryotes and much of the current knowledge in these fields has stemmed from such work. Importantly, the proposed work will expand skills, training and experience for a RA1A and Technician. This project will provide a conduit for researcher progression to positions that positively impact on academic and industrial sectors, addressing the BBSRC's strategic objective: World-class people and careers.

UKRI Gateway to Research · FY 2026 · 2026-01

Immune responses to pathogens are essential for human health. After seeing pathogens for the first time, our immune system can remember this encounter and respond to re-infection with the same pathogen more effectively. This process, termed ‘immunological memory’, is vital in allowing us to deal with repeat infections, and is also the cornerstone of successful vaccination. Key cells in promoting memory responses in the immune system are T-cells. These cells are activated during initial infection, with most dying off when the infection is cleared, but some becoming long-lived memory T-cells that respond more quickly and effectively to re-infection. Understanding how memory T-cells function is therefore crucial in understanding how we successfully fight infection, and in the design of vaccines to promote immunological memory. Our exciting new data has identified an unexpected role for a subset of memory T-cells in regulating responses to re-infection. Thus, a proportion of T-cells previously classified as CD4+ effector/memory T-cells have the ability to activate the cytokine TGF-beta and play an unexpected role in keeping the brakes on the T-cell response during viral re-infection in the lung. In the absence of this pathway, more damage occurs in the lung during re-infection. Thus, we have uncovered a pathway that appears to limit the immune system during re-infection to prevent unwanted inflammation and tissue injury. It is now critical that we determine in detail the properties and characteristics of these cells, why they are specialised to suppress tissue damage during re-infection, and whether they function during specifically during viral re-infection in the lung or to other immune challenges as well. Additionally, we have discovered that these suppressive memory T cells are present in tumours, where they may play roles in suppressing anti-tumour immune responses. The overarching aim of this project is to investigate how a newly identified sub-population of CD4+  T-cells regulate immune responses to lung re-infection and determine the broader importance of this pathway in other tissues, and cancer. This will be achieved via the following three aims: Aim 1: Investigate the molecular, functional, and spatial characteristics of suppressive CD4+ effector/memory T-cells that limit immunity during lung re-infection. Aim 2: Determine the broader role of suppressive CD4+ effector/memory T-cells in inflammatory challenge. Aim 3: Examine the role of suppressive CD4+ effector/memory T-cells in regulation of cancer immunity. The enhanced understanding generated will provide fundamental insights into how immunological memory is regulated to help us balance responding robustly to pathogens upon re-infection without causing tissue damage. Our work will also determine other situations where these pathways act and could be targeted in disease or exploited therapeutically – for example targeting these cells to enhance immune responses in cancer.