Adult human retina harbours a population of Müller cells with stem cell characteristics. Although these cells have the ability to grow and neurally differentiate in vitro, there is no evidence that they regenerate retina in vivo. It has been thought that factors released during reactive gliosis, a glial proliferation observed in all retinal degenerative conditions, are responsible for the inhibition of retinal regeneration by endogenous stem cells. The proposed research aims to identifiy factors that may promote neural regeneration of diseased retina by stimulating the endogenous proliferation and neural differentiation of Müller stem cells. Using proteomic approaches, we will investigate the total protein and cytokine expression profile of fragments of human gliotic retina, surgically removed as part of the treatment for complicated retinal detachment, and will compare this profile with that of normal cadaveric donor retina. Factors found to be selectively increased or decreased in degenerated retina will then be examined for their ability to inhibit or promote Müller stem cell growth and differentiation in vitro. Once candidate factors have been found to be active on the inhibition or promotion of these cell functions, we will confirm their roles by blocking or promoting their activities using agonist or antagonist molecules for these factors. The work will be undertaken in collaboration with Prof. Sun Xinghai and Dr Lei Yuan from the Eye Hospital at Fudan University, Shanghai. The proteomic analysis will be performed at the UCL Institute of Ophthalmology and is expected to identify candidate factors which can be examined by both the UK and the Fudan group on Müller stem cell growth and differentiation. The project will form part of a PhD training program for a Chinese student who will visit the UCL Institute of Ophthalmology for a year. Funding for her visit and that of Prof Sun and Dr Lei, her PhD supervisors, is being sought by the Fudan University group from the Natural Science Foundation of China.

The global oceans act as a sponge, soaking up significant amounts of the excess heat and carbon that have been added to the atmosphere due to human activity. Our oceans therefore play a key role in buffering the magnitude of climate change. However, the future storage capacity of the ocean sponge is uncertain, alongside the distribution of nutrients and oxygen, key ingredients for a healthy marine ecosystem. To address these uncertainties, we need to better understand how the oceans flow deep below the surface layers - in particular current flows that span scales of tens of metres to hundreds of kilometers, otherwise known as submesoscales. Submesoscale currents matter because they provide a pathway to harness energy from the winds and tides and use it to stir and mix different water masses around the globe, along with the heat, carbon and nutrients that they carry. Despite their importance, little is known about ocean submesoscales because of their intermediate size and intermittent nature. This means they are both difficult to capture in nature or model with computers. In this project, my team will conduct a pioneering experiment that will capture for the first time the full range of current flows that exist beneath the surface ocean layers, alongside the mixing and stirring that they generate. A targeted sea-going programme using active acoustics will sample the ocean at unprecedented resolutions (two orders of magnitude better than other techniques) and fully capture submesoscale currents. Similar to how bats echo-locate, a ship at the surface releases sound pulses into the water and records reflections from water layers. Acoustic measurements will be combined for the first time with cutting-edge robotics, vessel-mounted and moored instrumentation. In parallel, state-of-the-art model simulations will be both validated and improved using our new ocean observation data. The result will be the most realistic representation of the sub-surface ocean to date. The simulations will be used to quantify submesoscale initiation, ubiquity and interactions, and assess their role in driving energy and property exchanges in the global ocean. The experiment will take place at a global hotspot of ocean activity: the Brazil-Malvinas Confluence off the coast of Argentina. Here sub-tropical waters from the Atlantic collide with polar waters from the Southern Ocean. Water mass exchanges at this confluence, which are likely driven by submesoscale currents, play a key role in the distribution of heat, salt, carbon and life sustaining nutrients and oxygen throughout the global oceans. By revealing interior ocean dynamics in unparalleled detail at the Brazil-Malvinas Confluence, COSSMoSS will shed light on a significant missing piece of the scientific ocean puzzle helping us to better understand our future biosphere and climate.

The operation of modern day electronics depends upon electric currents that transport electron charge. However, the electron also possesses intrinsic angular momentum, known as "spin", that is responsible for its magnetic moment. Spin is a quantum-mechanical quantity with two allowed values. We can therefore think of the electron as the smallest possible bar magnet with its north pole pointing either up or down. Ordinarily an electric current transports equal numbers of electrons in the up and down states. However, inside a ferromagnetic material there are more electrons in the up state than the down state; this is the origin of its magnetic behaviour. This means an electric current drawn from a ferromagnet will have a preponderance of up spins. In fact, under certain circumstances in non-magnetic metals, we can arrange for equal numbers of electrons with up and down spins to move in opposite directions so that there is a flow of spin angular momentum without any flow of charge. This is what is meant by a pure spin current. Within a ferromagnet an additional mechanism is available to transport spin current. Rather than the electrons moving, we can think of one electron flipping its spin from up to down and the location of this flipped spin moving from one atom to the next. This mechanism is present even when the material is an electrical insulator and is known as a "spin wave". Ferromagnets are only one of many types of material that have magnetic order. This proposal is concerned primarily with antiferromagnetic materials, where the direction of the spin alternates between up and down for successive layers of atoms. Antiferromagnets have no net magnetic moment, because those on adjacent atoms cancel out, so are generally more difficult to study, and for a long time were thought to be useless in terms of practical applications. However, spin waves also occur in antiferromagnets and so antiferromagnets can be used to transport pure spin current. It was recently observed that the amplitude of a spin current can be enhanced by the insertion of thin antiferromagnetic layers into a stack of ferromagnetic and non-magnetic layers. We have shown that the antiferromagnetic layer is able to transport both dc and ac spin currents, confirming a model that also predicts that spin currents could be amplified by at least a factor of 10 if the thickness of the layer is chosen carefully. This additional angular momentum is drawn from the crystal lattice. Given that a small electric current is usually required to generate a pure spin current, the ability to amplify spin current in the antiferromagnetic layer means that the energy efficiency of devices using spin currents could be significantly improved. One immediate example is a type of magnetic random access memory (MRAM), where spin current is injected into a ferromagnetic layer to reverse its magnetization so as to represent a 0 or 1 in binary code. Reducing power consumption by just a factor of 2 would already make MRAM an attractive alternative to dynamic random access memory (DRAM) within data centre applications. In this project, we will use an ultrafast laser measurement technique to first observe the spin wave modes that exist within antiferromagnetic thin films that may be the order of 10 atomic diameters in thickness. This will be a major achievement since ultrathin films can behave very differently to bulk crystals, and methods for observing their spin waves have yet to be demonstrated. Once we have this information, we will then be able to design multi-layered stacks in which to observe the propagation and amplification of spin currents. Specifically, we will use a time resolved x-ray measurement technique at a synchrotron source that we have already developed and demonstrated. Finally, we will explore how the stacks can be optimised so that they can be used in practical applications such as MRAM.

Antimicrobial resistance (AMR) and particularly resistance to antibiotics (ABR) has become one of the most complex public health challenges globally. Estimates have suggested that by 2050 AMR will be responsible for 10 million deaths, of which 4.73 million are in Asia, with an associated reduction of 2% to 3.5% in Gross Domestic Product (GDP) that will cost the world up to 100 trillion USD. Our collaborative research and training programme will bring together international experts at leading universities in China and the UK to tackle antibiotic resistance, the type of AMR that is the most pressing concern for human health. China is estimated to be the second largest consumer of antibiotics in the world, with widespread and often inessential use in both humans and livestock. Widespread consumption leads to antibiotic residues in water and soil that may exacerbate the development and transmission of resistance through organisms and chemicals in the environment. Studies have investigated the epidemiology and pattern of drug-resistant infections in China, but the size of the health and economic burdens caused by ABR on a national level and the role of the environment in the development and transmission of drug resistance are still unclear. Most ABR research in China has focused on specific bacteria in hospital patients, selected food animals, or isolated determinants. Better evidence and broader understanding of environmental, community, economic and health care drivers and burdens of ABR based on a systems perspective that recognises interactions between these areas is urgently needed, as are evaluation tools to measure the effectiveness of different ABR-reducing intervention strategies. Due to a dense population, an intensive livestock breeding industry and massive antibiotic use, Eastern China is a key region for controlling antibiotic use and ABR. Our research aims to bridge these key evidence gaps and strengthen disciplinary and methodological research skills, through a set of closely linked projects that will generate the holistic knowledge which is needed to design, deliver and monitor targeted strategies to limit ABR in China and comparable settings. We will also establish sustainable partnerships with cross-disciplinary research expertise that is currently lacking in China and strengthen capacity in policy-relevant research. Since antibiotic resistant infections and their genetic components spread rapidly through international travel, research into ways of reducing the burden of ABR in China is important not only for populations in China and the wider Asian region, but globally. Through three linked programmes of work based at three leading universities in China, supported by UK academics from a wide range of disciplines, we will: 1. Estimate the economic burden of AMR and determine the cost-effectiveness of potential intervention strategies 2. Design and evaluate a tailored intervention to modify antibiotic prescribing behaviour among health professionals and reduce antibiotic consumption among outpatients 3. Measure human exposure to antibiotics from environmental and livestock sources, estimate their health effects & develop tools for risk assessment and monitoring of environmental exposures to antibiotics and antibiotic-resistant genes 4. Gather evidence on current patterns of antibiotic use and the implementation of ABR-related policies and regulations at local, regional and national levels 5. Produce evidence-based recommendations on optimising antibiotic use, monitoring ABR and assessing the success of strategies to reduce ABR in China 6. Build cross-institutional and international collaborative groups to increase China's research capacity in a range of relevant disciplines and methodologies, as well as in the design and conduct of inter-disciplinary research.

The applicant is an experienced researcher and has a broad background in physical chemical characterisation, whose principal research interests include the synthesis, functionalisation and characterisation of advanced and nanostructured electro-materials for applications such as bionics, sensors, and energy storage. The applicant has pioneered the use of carbon nanotubes fibres as possible implantable electrode materials, when previously they were known for their exceptional mechanical properties. Novel fibres were developed, the electrical properties of which far exceeded that of previously made bio-fibres. The methods developed allowed fibre formation with broad material applicability. A challenge for nanomaterial research is aggregation. To allow the extraordinary properties of nanomaterials to be fully exploited, they must be effectively dispersed and integrated into useful devices. Following appropriate dispersion these materials lend themselves to processing by fibre spinning. Flexible fibre electrodes have to date been produced almost exclusively from carbon. Recently, we published the first report combining a metal oxide nanotube with carbon nanotubes to create multi-functional fibre electrodes for biomedical applications. Since it has been shown that it is possible to spin fibres from titania nanotubes it should also be possible to extend the range of nanotubes to those made from other materials. More recently in a very exciting development, researchers have combined graphene sheets with CNTs to produce macroscopic fibres with extraordinary strength properties. Combining the high electrical conductivity we previously achieved, with the strength of intercalated graphene and sustainable energy storage capabilities of manganese dioxide will enable the fabrication of highly novel and patentable flexible fibre electrodes. This proposal aims to broaden the scope of our initial studies by incorporating nanotubes of manganese dioxide with carbon nanotubes and graphene, for the first time. We will demonstrate this approach by fabricating a novel flexible fibre electrode for sustainable energy storage. The overall aim of the proposed research is to fabricate fibre supercapacitors, which can be woven to make energy storage options for e-textiles.