Epithelia are layers of cells that cover body surfaces and line internal organs. They form functional barriers that protect us from the environment and enable our organs to generate and maintain compartments of different compositions, such as the barrier that separates the retina from the blood at the back or the eye. For individual epithelial cells to interact and form epithelial tissues, they need to assemble adhesive complexes with neighbouring cells. One of these adhesive complexes is called tight junction and forms a barrier in between neighbouring cells; hence, tight junctions are essential for epithelia to form tissue barriers as they prevent random diffusion along the space in between neighbouring cells. Consequently, the integrity of tight junctions must be maintained in order to prevent epithelial barrier breakdown and tissue failure. However, epithelial cells are often under physical strain and undergo cell shape changes during cell division or during the development of our organs and tissues. Therefore, mechanisms are likely to exist that allow tight junctions to adapt to changing cell shapes and, possibly, help cells sense and adapt to external physical forces that act on tight junctions. Here, we focus on the questions of whether such mechanisms exist and how such molecular bridges are built. Tight junctions are composed of many different proteins that form a molecular network that starts with cell-cell adhesion proteins at the cell surface by which cells interact with each other. These cell-cell adhesion proteins interact with a large range of proteins inside the cells that regulate the various junctional functions and that are thought to function as molecular scaffolds that support the structure of tight junctions. Some of these proteins can also interact with the cytoskeleton, a network of protein fibres that supports the cell's structure and shape. However, the functional relevance of these interactions is not well understood. We hypothesized that components that can interact with the cell-cell adhesion proteins at the cell surface and the internal cytoskeleton might work as force transducing linkers. Hence, we have constructed a sensor based on such a protein that allows us to determine whether the molecule is indeed under tension. Pilot experiments indicate that the sensor is functional and that tight junctions are indeed a force-bearing structure. Our objectives now are to determine the junctional architectural principles that enable tight junctions to bear forces and transduce them between the cytoskeleton and the cell surface, and to make use of functional assays to determine the physiological function of these principles for epithelial tissue formation and development. The expected results will help us to understand physiologically important processes relevant for organism development, and tissue function and regeneration. They will contribute to our understanding of common diseases that disrupt epithelial tissues such as cancer, viral and bacterial infections, and common chronic inflammatory and age-related conditions. We also expect that the results and principles to be discovered will support tissue engineering and regenerative medicine approaches.

This research project uses a novel methodological approach to determine where mineral dehydration reactions can trigger failure in deforming rocks. This link between dehydration and failure is important at convergent plate boundaries. Where plates collide, the shallow portions of the Earth's crust are affected by so-called thin-skinned tectonics. There, dehydration reactions enable the emplacement of tectonic nappes, which shape mountain belts such as the Swiss Jura, or the Appalachians in the US. Plate collision also leads to the subduction of tectonic plates, where dehydration reactions are suspected to trigger seismic events at depths of several tens of kilometers. In both tectonic settings hydrous minerals in rocks become unstable as temperature increases. They start to transform into denser minerals by releasing water in dehydration reactions. The density increase produces pores, which are filled by the water. The pores, the fluid pressure in them, and the newly grown minerals weaken the reacting rock mechanically. It may become unable to support tectonic stresses and fail. The processes that control large-scale tectonics start at the grain scale. These grain scale processes entail a series of complicated, intertwined developments that involve the chemistry, hydraulics and mechanics of a dehydrating rock. Coupled chemical, hydraulic and mechanical processes may facilitate the self-organization of the dehydrating rock into a state where it ultimately fails. Unfortunately, neither classical laboratory experiments nor field-based studies allow a spatial and temporal (4D) characterization of these coupled processes on the micro-scale. Models to explain failure in dehydrating rocks therefore lack a robust observational basis. We will use a unique combination of new methods to overcome this severe limitation. Our interdisciplinary team of experienced researchers will establish a technique to directly observe dehydration reactions in deforming rocks. We will employ the most powerful x-ray sources in the UK and Switzerland to observe dehydration reactions in a new generation of experimental pressure vessels. These vessels are transparent to x-rays and allow us to reproduce conditions at the base of tectonic nappes and at intermediate depths in subduction zones. They are designed and built in Edinburgh. Combining these vessels with time-resolved (4D) x-ray microtomography will enable us to document mineral dehydration at a wide range of conditions. The resulting 4D microtomography data sets will have a volume of several tens of TB. New analysis techniques based on machine learning will allow us to extract the relevant information from these vast quantities of data. Our analyses will determine conditions where dehydration causes rocks to become unable to support tectonic stresses. Using these analyses, we will test and advance theoretical concepts used to link dehydration and deformation in numerical simulations. The first direct observation of the complex grain-scale developments during dehydration reactions will significantly advance our understanding of some key processes in tectonics. Because our data are time-resolved and dynamic, they will support the interpretation of field data that otherwise capture a static, fossilized picture of dehydration reactions. Our data will allow testing and refining existing mathematical models that provide a foundation for robust simulations of large-scale tectonic processes. Ultimately, our findings will support the assessment of risks associated with plate collision. Our project will also make a new experimental imaging method available for research on geothermal energy, CO2 sequestration and nuclear waste storage. The method combines time-resolved x-ray microtomography in our new experimental vessels with advanced data mining and image analysis and computational simulation.

Energy is one of the most important issues of the twenty-first century, because our future supply is currently threatened by progressively decreasing fossil fuel reserves, political instability and environmental problems resulting in pollution and global warming. Renewable hydrogen, H2, is widely considered as a potential future fuel, but its cheap and efficient production is still a major unresolved practical issue. The sun provides our planet with a continuous flow of electromagnetic and carbon-free energy and it is the only energy source, which is capable of sustaining human kind's long-term energy demand. The aim of this EPSRC-funded project is the development of an efficient bio-inspired H2 production catalyst from abundant and inexpensive raw materials and its coupling to light-harvesting complexes to capture energy provided by the sun to power H2 production from water - the storage of solar energy in the chemical bond of H2.Selective and economical chemical catalysts are needed for the central chemical interconversion of energy, water and H2 if there is to be a real prospect of promoting H2 as a sustainable fuel. Commonly employed precious metal catalysts (e.g. platinum) cannot be used for H2 production in the post-fossil fuel era, because of (i) limited resources and high cost, (ii) poor reaction selectivity (e.g. energy is wasted on unwanted side-reactions), and (iii) poisoning (catalyst-killing) by trace amounts of common chemicals, e.g. carbon monoxide. Microbial life forms handle the challenging task of H2 production using bio-catalysts (hydrogenases) to drive the selective and reversible production of H2 from water at fast rates under the safe conditions of room temperature and neutral pH. The catalytic reaction centre (active site) of hydrogenases contains an iron or nickel-iron metal centre surrounded typically by cysteine, carbon monoxide and cyanide ligands. Thus, the active site of a hydrogenase is an interesting biological motif to mimic in order to build H2 production catalysts from abundant and inexpensive raw materials. This adventurous work on solar H2 production has the prospect of being a fundamental step towards large-scale water photolysis for a sustainable hydrogen economy. International (France, USA) and national (Manchester) academic as well as industrial (Evonik Industries) collaborators with expertise in enzyme biology, spectroscopy, solar cells, nanoparticles, and neutron diffraction will support this project under my guidance. In addition, this work on bio-inspired/biomimetic H2 production catalysts will also deal with wastewater treatment, the synthesis of fine chemicals, and might give us insight into how living organisms convert water into H2 on a molecular level, and reveal how the reverse reaction works: the generation of energy from H2, which is important for fuel cell applications.

Subglacial hydrology is a critical control on mass loss from the Greenland Ice Sheet via its impact on ice motion in the ablation zone and frontal ablation of marine terminating glaciers. Subglacial lakes are a key component of this subglacial hydrological system. Sediments that accumulate on lake beds are potential archives of past ice sheet configurations, paleoenvironmental and palaeoclimate change, and the presence of life. Subglacial lake water provides a habitat for microbial communities and an analogue for life on other planetary bodies. The localised storage and downstream drainage of large volumes of water modulates basal hydrology and biogeochemical cycles/processes, and can trigger calving at the ice margin and transient (weeks to months) and long-term ice-flow variations. Drainage events can also form channels, cut up into the ice or down into the bed, and transport large volumes of water and sediment downstream. Finally, outburst floods onto the glacier foreland present a major hazard to downstream life and infrastructure. Although it is well documented that hundreds of subglacial lakes exist beneath the Antarctic Ice Sheet, in Greenland, subglacial lakes have until recently received little attention because the geometry of the ice sheet led to the assumption that they were scarce. However, recent work from members of our team demonstrate that lakes are widespread beneath the Greenland Ice Sheet and moreover, can be highly dynamic features that, in contrast to Antarctica, are fed by melt from the ice surface and can drain rapidly in a matter of weeks. They therefore represent an important end-member for how subglacial lakes in both Greenland and Antarctica will behave in a warmer world as surface melting becomes more prevalent, accesses a wider portion of the bed, and lake drainage becomes more vigorous. Yet the key processes controlling subglacial lake formation and dynamics, and their impact on basal hydrology and ice flow in Greenland have yet to be identified. What is needed therefore is detailed field data integrated with numerical modelling to accurately determine the properties of these environments and assess their influence on ice sheet subglacial hydrology and ice dynamics. The project will assemble a world-leading multidisciplinary team to undertake the first field-based characterisation and monitoring of multiple fast-draining subglacial lakes in Greenland, which will be used to constrain and test a state-of-the-art subglacial hydrological model. It benefits from the confirmed discovery of three fast-draining subglacial lakes beneath Isunnguata Sermia, which are the most accessible on the planet and therefore provide an opportunity to conduct high-reward discovery science with logistical economy and low risk. The aim is to quantify the role of fast-draining subglacial lakes on the hydrology and dynamics of the Greenland Ice Sheet to: (i) improve our understanding of the role of subglacial lakes in modulating subglacial hydrology and dynamics in Greenland; (ii) provide insight into their future impact in both Greenland and Antarctica, (iii) generate data to enable ice sheet and hydrological modellers to improve their predictions of the future contribution of the GrIS to sea level rise, and (iv) develop the scientific basis for future subglacial lake exploration in Greenland for investigating past ice and climate change and exploring subglacial biology and biogeochemical fluxes.

Satellite observations provide glaciologists with increasingly complete and frequent maps of ice velocity and thickness changes of the Antarctic Ice Sheet (AIS). For nearly three decades, satellites have helped us identify the physical processes that underlie contemporary rates of mass loss from the AIS, and have been key in quantifying Antarctica's present-day contribution to global sea level rise. However, the fundamental issue remains how these changes will evolve in a warming world, and what their global impact will be on sea level, climate and ecosystems. In order to provide reliable forecasts of ice sheet changes, and CONNECT the past, present and future, we need validated models with robust uncertainty quantification. This is what this project offers. In parallel with the satellite revolution, ice sheet models have advanced significantly over the last decade. Confidence in their ability to produce numerically robust projections for complex geometries and 'external' forcing has greatly improved, and essential dynamical interactions with the ocean and atmosphere can now be included. Yet, no systematic attempt has been made at comparing hindcasts of past changes from modern ice flow models with the rich, 30-year repository of satellite data from Antarctica. A model validation exercise of this type is both timely and critical: it needs the long time series of observations and sophisticated models that are now available, and it forms a prerequisite for reliable forecasts of the AIS's impact on global sea levels in the 21st century. In light of this important deficiency in ice sheet modelling and the need for robust, century-scale forecasts, De Rydt and his team of PDRAs and international project partners will address three distinct challenges: (1) the initial value problem of predicting the evolution of the Ice Sheet given an uncertain estimate of its present-day state, (2) the structural problem of unknown/uncertain physical parameters, and (3) the boundary value problem of assessing future changes in the state of the Ice Sheet due to uncertain future climate forcing. Building on De Rydt's internationally recognised expertise in ice dynamics and ice-ocean modelling, the team will first generate a best estimate of the state of the AIS in the 1990s through data assimilation in a coupled ice-ocean model, and perform the first circumpolar Bayesian uncertainty analysis to quantify how errors in the initial conditions are amplified by forward integration with realistic forcing between 1990 and 2020. Next, they will use newly developed techniques in perturbed physics ensembles in combination with model emulators to systematically sample uncertain model physics (basal sliding, ice rheology, calving, etc) and assess their impact on forecasts within a probabilistic framework. This will allow them to comprehensively validate a next-generation coupled ice-ocean model for the first time and identify the physical parameter space that is consistent with observations. Finally, they will use output from a range of global climate simulations in combination with perturbed physics ensembles to obtain an improved estimate of ice loss from the AIS between now and 2100, with a robust quantification of all model errors and consistent with the observational record. The project will foster international collaboration, bring significant advances in the field with broader societal impact, and establish the PI and his team as world-leaders in the field. Key findings will be published in high impact scientific journals and contribute to future IPCC reports. Through partnerships with NUSTEM and the International Glaciology Society and through project websites, public lectures, school workshops and social media channels, the team will communicate about the wider societal and environmental aspects of sea level rise with key stakeholders in climate policy, young people and their influencers in North East England, and a worldwide audience.