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Inflammation, the most important response of our 'Innate Immune System', is a normal defence mechanism that protects from infection and repairs damage caused by trauma (e.g. wounds). However, the full benefits of inflammation are only realised when the response is turned off and the infected or traumatised tissue is returned to normal. This process is known as 'resolution' and is essential to successful wound healing facilitated by immune cells. When this process is defective it can 'stall' leading to damaging chronic inflammation and non-healing wounds. By studying the resolution of inflammation and understanding the mechanisms by which immune cells communicate with each other, we have identified crucial factors that drive resolution and thus support wound healing. These factors are small membrane bags (called extracellular vesicles: EV) which carry important cargo - active signals that flick the switch in inflammation from defence to repair. This switch is present in important immune cells - macrophages - and switches the cell from an M1 (defence) phenotype to an M2 (repair) phenotype to resolve inflammation. EV are therefore crucial in resolving inflammation. Why is this important? Poor wound healing is a major challenge especially with the advancing age of our population and incidence of important co-morbidities such as diabetes. Estimates suggest that each year 3.8 million patients are managed by the NHS for wounds, with over 130 million patient visits from healthcare staff, at an annual NHS cost of £8.3 billion, of which £5.6 billion is associated with managing non-healing (chronic) wounds. Consequently, there is an urgent and unmet need to understand and exploit the immune control that is impaired with ageing and to develop novel approaches to promote wound healing. In chronic (non-healing wounds) the resolution is 'stalled' in the inflammatory phase i.e. the switch is inactive in chronic wounds and our work has identified a route to reactivation of this switch. This proposed programme will exploit this to achieve impact in wound healing therapies by producing EV loaded with the appropriate 'switch' cargo. Our proposal brings together a strong multi-disciplinary team and cutting-edge technology to undertake key technical developments to move our research to the next stage of exploitation as a product to benefit wound healing. To do this we will take industry standard cell lines used for production of therapeutic agents and engineer them to carry the active cargo needed for switching to repair. We will then prove the ability of these engineered EV to 'flick the switch' in inflammation to repair in a manner that supports effective wound healing. This programme of work will deliver for the first time EV engineered to carry inflammation controlling cargo with a proven benefit in wound healing. This novel and fundamental development will have a significant impact in the field of wound healing and regenerative medicine. Our use of industry relevant cell and culture systems de-risks the programme for further development at the end of this project, ensuring the outcomes of our programme can be progressed rapidly to clinical trials.

The University of Edinburgh (UoE) is an international centre for soft matter research. Soft matter scientists study complex liquids in which there are structures intermediate in size between the small molecules making up the solvent and the macroscopic world of structures visible to the naked eye. The structures may be pigment particles in paint (colloids), self-assembled aggregates of soap molecules in washing-up liquid (surfactant micelles), bubbles (say, in whipped cream) or long-chain molecules (polymers) such as DNA (as used in gene transfection). The field is of fundamental interest because the properties of these materials are controlled by many competing length and time scales, and can change dramatically under everyday conditions. Such materials are also ubiquitous in formulations of all kinds, such as medicines (CALPOL is a suspension of colloidal paracetamol) and personal care products (a shampoo is a surfactant-polymer mixture). They are also key intermediates in many sectors: all ceramics, for example, begin as soft pastes (think potter's clay) that are pumped into moulds or extruded before they are sintered at high temperatures to form the final hard products. A fundamental challenge in soft matter is to figure out the way these intermediate structural elements are organised, and how such organisation changes in response to external forces. Most of such materials are opaque to light, so that optical microscopies of all kinds are not useful except to give surface information. As a result, scientists sometimes resort to various kinds of electron microscopy, which, however, operate in a vacuum, so that wet samples are desiccated and their native structures destroyed. A major development in the last decades is cryogenic scanning electron microscopy (cryo-SEM). A native, wet soft sample is frozen in liquid nitrogen, using special techniques to ensure rapidity of cooling to preserve intricate microstructures. Then these frozen samples are fractured, exposing internal structures to be imaged by SEM. (One disadvantage is that samples fracture more or less randomly, so that what is exposed to view is haphazard.) A single cryo-SEM instrument exists at UoE. This decade-old instrument is limited in both resolution (ten times worse than the best instruments today) and in access for soft matter scientists, as it requires laborious conversion of the system to cryogenic mode. We propose to purchase a state-of-the-art cryo-SEM to enable this cutting-edge technique to become routinely available for day-to-day work. This purchase is timely, because cryo-SEM has recently been revolutionised for soft matter researchers by the addition of focussed ion beam (FIB). This powerful technique uses a focused beam of charged atoms (ions) to cut and section specimens very accurately inside the SEM. This not only allows the user to expose desired sections at will, but also to build up a complete 3D picture (literally) by imaging the sample section by section to a resolution of 10 nm (100 times the size of atoms). We propose to purchase a cryo-FIB SEM. The technique is so new that we know of only two current instruments in the UK, neither of which is dedicated to the study of soft matter. We propose to add X-ray tomography capability to our cryo-FIB SEM. This allows us to build up a 3D picture non-destructively to 350 nm resolution, much like the way X-ray CT scanners build up 3D images of the body in hospitals. The availability of this combined suite of instruments will transform the ability of soft matter scientists to see inside their samples routinely. A host of exciting applications immediately follow. One example is 'designer electrodes' based on novel soft materials that minimise expansion/shrinkage during charge/discharge cycles. A programme of outreach and training will make this facility available to academic and industrial researchers UK-wide.

Repercussions of the semiconductor manufacturing crisis in 2021-2022 have highlighted how much modern society depends on semiconductor technologies. Semiconductors are an important part of the UK economy, with a market worth around $8bn in 2020 and still on the rising. Semiconductors are fundamental components of electronic and optoelectronic devices thus playing a key-role in the advancement of a number of seemingly unrelated technologies such as the field of microelectronics, the renewable energy sector and the communication sector. Traditional semiconductors such as silicon are getting pushed to the edge of their physical limits by the constantly increasing and often conflicting requirements of modern devices. van der Waals (vdW) semiconductors and related two-dimensional materials (2D) can provide a solution to these challenges due their ability to overcome some of the physical limitations affecting traditional semiconductors. This EPSRC New Investigator Award will support the growth of the UK semiconductor department by designing mixed-anions vdW semiconductors with new and improved functionalities, and a scalable deposition method to produce them. Prime example of vdW semiconductors are black phosphorous (BP) or transitional metal dichalcogenides (TMDs). Most vdW materials are either metallic or insulating. Only few chemical families, such as BP or TMDs possess semiconducting properties and can be exfoliated to 2D form. This limits the functionalities that can be accessed to those available in these chemistries. The variety of functionalities available in vdW semiconductors can be drastically increased if we leverage the properties of multiple anions to design new materials with new functionalities. This was recently demonstrated for CrSBr, a rare case of 2D ferromagnetic semiconductor. I will further advance this field by designing new mixed-anion vdW semiconductors belonging to the family of metal chalcohalides and metal oxyhalides that display high mobility of the electrical carriers, non-linear optical properties and room temperature ferroelectricity. To boost the manufacturability of these materials, I will modify the Polymer Assisted Deposition (PAD) method to enable simultaneous insertion of multiple anions at once. This method is scalable and cost-effective, thus suitable to rapidly move across the technology readiness levels (TRL) scale towards industrialization. The PAD method will also be pivotal in allowing the chemical flexibility to design materials with targeted properties based on the unique physical and chemical properties of the incorporated anions. For example, in oxyhalides, the choice of the halide will determine the size of the material's fundamental band gap, determining the material's ability to absorb or emit a different portion of visible light. This enables an atomic control over the materials' properties based on the anion inserted. The relevance of these materials for the semiconductor industry will be finally demonstrated by fabricating current rectifying devices (e.g., p-n junctions), whose properties must be equal or superior to those of the industrial standard, silicon.

Photovoltaic (PV) devices convert sunlight directly into electricity and so are set to play a major role in the global renewable energy landscape in the coming decades as humanity transitions to a low carbon future. Today's PVs are based on conventional semiconductors which are relatively energy-intensive to produce and largely restricted to rigid flat plate designs. Consequently, PVs that can be fabricated by printing at low temperature onto flexible substrates are attractive for a broad range of applications in buildings and transportation, where flexibility, colour-tuneability, light-weight and low cost are essential requirements. Two emerging PV technologies that have strong potential to meet these requirements are organic PVs and perovskite PVs. It is however widely recognised that these classes of PV can only fulfill their full cost-advantage and functional advantages over conventional thin film PVs if a suitable transparent, flexible electrode is forthcoming. Indium-tin oxide (ITO) is currently the dominant transparent conductor used in opto-electronics, including PVs. However, its fragile ceramic nature makes it poorly compatible with flexible substrates and indium has been identified as a 'critical raw material' for the European economic area, due to the high risk of supply shortages expected in the next 10 years. Consequently there is a need to develop a viable alternative to ITO and conducting oxide electrodes in general, particularly for utility in PVs where large quantities will be needed in the coming decades to help address the threat posed by global warming. This proposal seeks to address this challenge by developing a high performance transparent electrode based on a copper grid that can be integrated with the rest of the PV device by simple lamination. This approach avoids the inevitable compromises in electrode transparency and conductivity that arise when using the conventional approach of fabricating the transparent electrode directly on top of the rest of device. Two unconventional approaches to fabricating this electrode using low cost sustainable materials and processes will be explored. The outputs have the potential to be transformative for the advancement of OPV and PPV, as well numerous other optoelectronic devices requiring a transparent top-electrode. The UK is a global leader in the development of materials and processes for next generation PVs and so the outputs of the proposed research has strong potential to directly increase the economic competitiveness of the UK in this increasingly important sector and will help to address the now time critical challenge of climate change due to global warming.