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.

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.

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.

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.

All cells are covered in a forest of diverse carbohydrates structures known as the glycocalyx. There are many types of cell-surface carbohydrates (glycans) - some are long linear polymer chains, while others have short highly branched architectures like small trees. The composition of the glycocalyx is different for different types of cells - while the range of glycan structures present can be similar, the relative quantities of each glycan can vary considerably from one type of cell to another. Glycocalyx composition also changes if a cell becomes cancerous, and so measuring the composition of a glycocalyx presents opportunities for cancer diagnosis. Currently, the only way to measure how much of each type of glycan is present on a cell is to chop them off the cell, and weigh them individually in a mass spectrometer. The aim of this research project is to develop molecular tools that can be used to quantify how much of a particular glycan is present on an intact cell surface, and to bind with high selectivity to cells that have a particular glycan composition. These probes will have applications in understanding biological processes, and could ultimately be used as medical diagnostics and for targeted delivery of drugs to specific cell types. So how do you differentiate between two cells that have the same set of cell surface molecules, and differ only in the relative abundance of those molecules? Traditional probes like antibodies usually bind with high affinity to only one or two copies of their target molecule. They can be used to tell if a specific type of molecule is present on a cell surface, but not to bind selectively in response to a specific density of their target molecules. Density-dependent 'superselective' binding requires a different strategy that is inspired by glycobiology - the biology of carbohydrates. Carbohydrate-binding proteins often interact relatively weakly with their target glycan and strong interactions are achieved by having many copies of the glycans and glycan-binding proteins interacting with one another in concert - so-called multivalent binding. In this way, many weak interactions come together to enhance binding strength, but it also greatly enhances the selectivity of binding. Here we will develop multivalent probes that can bind in a density-dependent manner to cell surface glycans. We will develop probes that can distinguish between cancerous and healthy cells, and probes that can be used to map out complex net-like glycocalyces that regulate the function of neuronal cells. The methods developed will have much broader application for highly specific binding to target cells in both biology and medicine.