Potato late blight, caused by Phytophthora infestans (Pi), is a devastating disease of potato crops and led to the Irish potato famine of the 1840s. Most potato varieties are susceptible to blight, and its control costs ~£60M in fungicide applications in the UK, and ~$7B world-wide. Genetic resistance to blight would greatly reduce the need for agrichemical sprays and save on tractor journeys that emit CO2 and compact the soil. Plants have powerful defence mechanisms, but the key to resistance is recognition. Blight is a rapidly evolving pathogen, with many different races. As with antibiotics, reliance on one mode of action or one source of resistance is risky, and as with COVID, pathogens can rapidly evolve to cope with resistance mechanisms. We have deployed a stack of 3 Resistance to Pi (Rpi) genes in a potential new variety ("PiperPlus"), but more Rpi genes are needed in anticipation of pathogen evolution, and also to enhance our understanding of plant/pathogen coevolution, and pathogen virulence mechanisms. Our primary objective is to understand the near-immunity to late blight of the potato relative Solanum americanum ("Sam"), the diploid ancestor of the widespread UK native plant black nightshade (S. nigrum). We have 54 different accessions from around the world, but all are fully resistant in the field, though some show susceptibility under disease-promoting lab conditions, which enabled us to use genetics to clone two Resistance to P. infestans (Rpi) genes, Rpi-amr1 and Rpi-amr3. Because we have cloned the Pi molecules (Avramr1 and Avramr3) that are recognized by Rpi-amr1 and Rpi-amr3, we could identify many additional "non-amr1,3" resistances in our collection. We have extensive Sam genome sequence data that greatly helps analysis of genetic variation for detection of and resistance to Pi. A central goal of this proposal is to clone multiple additional resistances and to verify their efficacy against multiple races of Pi. We are confident there at least two additional resistance genes in our set of accessions; Rpi-amr5 from Sam accession SP2275 (perhaps but not necessarily the same as Rpi-amr12 from SP3370), and Rpi-amr13 from SP2300 (perhaps but not necessarily the same as Rpi-amr15 from SP2298) and Rpi-amr14 from SP1101. Genetic mapping to identify these new Rpi genes is well advanced and will be completed and published during the grant period, with function verified in transgenic potato plants Since Sam is so resistant, it is likely to have many different ways of recognising Pi. We have identified another 7 virulence components from Pi that are recognised in at least one Sam accession, and are well on the way to identifying the Sam gene that underpins each of these recognition capacities. One is already cloned. We hypothesise that these multiple recognition capacities contribute to resistance. We will test this in two ways (i) we will test if transfer of these additional recognition capacities into potato, alone or in combination, can elevate resistance tp Pi. (ii) we will use the recent "CrispR" technology for targeted mutagenesis to mutate three of these genes in accession SP2271, and test if reduction in recognition capacity compromises resistance and elevates susceptibility Pathogen effectors have evolved to promote their reproductive success when growing on their hosts. Effectors contribute to pathogen virulence by interfering with plant mechanisms that are part of the plant defence response. By identifying the host target of a pathogen effector, we identify key components of plant defence mechanisms. Thus, every new resistance gene isolated not only helps enable durable disease resistance, but also provides a route to identifying the recognised molecule that is a key pathogen virulence component, and therefore also their plant targets, enabling us to greatly enhance our understanding of plant immunity.

The speed of a wave moving through a material is set by the refractive index; something immutable we might look up in a table and perhaps promptly forget. But imagine having the power to change it at will. What could we do? It would allow a single object to have different functions: a chassis that becomes transparent at the flick of a switch, or a room that can be made instantly private, turning thin walls into sound absorbers. Yet these ideas are just the beginning of the story. If we can rapidly switch the wave speed, then completely new effects emerge. For example, changing the refractive index abruptly causes a wave to "reflect in time" - a paradoxical temporal analogue of the ordinary reflection we see and hear every day (e.g. the echo from a wall), but one that can cause the wave to gain energy. Other new effects arise if we can also change the refractive index differently at each point in space. With this control it becomes possible - for instance - to make a stationary object look like it is moving. Unlike true motion there is no restriction on this speed, and we can even mimic objects moving faster than light! Our research will develop new materials where the refractive index can be changed in time, exploring switchable functionality and the plethora of new wave effects that emerge when the material properties are varied rapidly. This is not always an easy thing to do and to avoid potential obstacles to our research we take a "wave agnostic" view, where we - in parallel - explore the effects of a time varying wave speed for airborne acoustic waves, mechanical vibrations, radio frequency waves, terahertz waves, and in optics. To illustrate the huge advantage of this approach, consider the time scales involved: "rapid" means the change must be imposed more quickly than the wave oscillates. For audible sound this is milliseconds, for visible light femtoseconds. We should use very different techniques in these two cases! In optics, special materials are subject to ultra-fast, high-intensity fields, while in acoustics we use electronically controlled transducers. Through considering different wave regimes we can implement a time varying wave speed by the most promising means, avoiding the limitations of any individual technique. Our program of research is split into four, first developing experiments to demonstrate rapid switching of acoustic, elastic, and electromagnetic wave speeds in time, and the theory required to design them. The second part pushes this work to the next stage, developing materials where the wave speed varies in both space and time, allowing us to e.g. mimic motion. Having developed these experimental and theoretical capabilities, the final two parts of the project explore new wave effects in these materials, specifically wave amplification and unusual materials where the wave can only propagate in one direction. While our research is a fundamental study into wave physics in time-varying materials, we predict multiple applications of this technology. Future communications (6G) is perhaps the simplest. This will need an enormous number of separately powered antennas to precisely direct beams of electromagnetic waves. But if we can rapidly change the reflective properties of a surface next to a single antenna, we can make it alone perform the function of these many different antennas, reducing energy requirements and complexity! Wave-based computing is a second example: like every physical process, the scattering of a wave from a material is equivalent to a computation. Although electromagnetic waves perform this computation very quickly - at the speed of light! - to use it as a "computer" we need to program it. The material properties are fixed, so the wave always scatters in the same way. If we can switch the material properties, we can program it and create a new class of high-speed computational devices based on wave-scattering.

In recent times, our enthusiasm for "disposable" plastics culture has been replaced by a more environmentally and carbon-conscious ethos that has created a strong desire amongst consumers and producers for greater use of recyclable or biodegradable materials. Whilst there are already some examples of such plastics in use (e.g. shrink wrapping for magazines or BioWare plates and cutlery) their relatively low volumes of usage, slow breakdown rates in the natural environment and widespread confusion with conventional plastics mean that this little more than a token effort at present. Similarly, while reducing single-use or unnecessary plastic packaging is very important, some packaging is still required to maintain food quality, shelf-life and international distribution networks. With this project, we plan to supplant the widespread use of fossil-derived plastics with materials made from naturally derived sources, such as wood (cellulose) and plants (sugars). These materials will degrade more easily in the natural environment, and result in no additional carbon being returned to the biosphere. By changing the genetic code of the plants, or blending with other additives from food or agricultural waste, we can engineer materials with new functional properties, such as improved strength or better protection, resulting in a reduction in overall volume of plastic packing used to keep food fresh. We will also ensure that these new plastics are compatible with existing recycling infrastructure to enable maximum reuse before degradation. Of course, changing wholesale from fossil-derived to plant-derived feedstocks will entail major changes to our economic and environmental processes. At present, many sources of natural feedstocks are in direct competition with food resources and are unprofitable to produce at large scales compared with feedstocks for conventional plastics. By assessing the impact of switching to plant-derived sugars and making better use of waste products from food and forestry industries, we will explore the trade-offs between the benefits of plastic packaging and the impacts of its production and disposal, both for existing plastics and new natural feedstock alternatives. Success of the project will result in fulfilment of many of the UK Plastic Pact 2025 challenges and help to achieve the objective of establishing the UK as a leading innovator in smart and sustainable plastic packaging.

Obesity and associated conditions such as type 2 diabetes and cardiovascular disease are major global health concerns. A contributing factor is overconsumption of energy dense foods, rich in fat and sugar, driven by our hedonic and physiological desire to consume energy rich foods. One approach has been to reduce the energy content of foods whilst retaining the sensorial quality. The food industry has developed a wide range of healthier products. In order for these products to be successful, consumers must continue to purchase and consume them. However, recent studies have suggested that reducing the energy content of a food may have unintended consequences. Specifically, if a food looks, and tastes like it is rich in nutrients, the gut and brain systems prepare to expect a high energy intake. If this does not happen, as in the case of a reduced calorie food, the brain appears to induce hunger signals that drive the individual to overconsume at subsequent meals (rebound hunger), resulting in an increased calorie intake, thus negating the whole effect of consuming the reduced calorie food. This leads to consumer dissatisfaction with these products, and potentially to imbalances in appetite and hunger hormones that often cause rapid weight gain following periods of dieting. Therefore we need to rethink how reduced calorie foods can be used more effectively to control energy intake. To do this, we need to understand the relationship between how we sense foods, how we digest and absorb the nutrients and how the brain responds to these processes and controls subsequent appetite signalling. This Mouth-Gut-Brain system is key to controlling our appetite and energy intake. The aim of this project is to understand how the mismatch between sensory properties and nutrient intake of food controls our appetite and rebound hunger. The key question we aim to address is, by how much can the energy content of a food be reduced before rebound hunger and overconsumption occurs? The key impact will be our ability to modify reformulated foods to reduce the gap between sensory and nutrient signals in order for reduced-energy alternatives to satisfying and not result in subsequent over-consumption. This project will focus on fat, as fat has the highest energy content, and the sensory properties of low fat foods are challenging for both consumers and the food industry. We will investigate the impact of reducing the fat content of foods by determining how the sensory properties control consumer expectations of satiety (feeling of "fullness"), and measure how much we can reduce fat content before consumers develop rebound hunger and overconsume at a subsequent meal. Using this information we will design a more realistic food where the structure, physical behaviour and sensory properties are closely matched, but with a range of fat contents and fat type, to carefully control how much fat is "sensed" and how much is absorbed. We will measure how the appetite response of these foods controls the consumption of food in a following meal; and study differences between individuals who are sensitive or insensitive to fat content in foods. This will determine how much we can alter the sensory and fat content of food and still maintain an overall reduction in energy across subsequent meals. Results will provide valuable information on how mouth-gut-brain signalling fundamentally controls appetite, and begin to unravel why different individuals may be more susceptible to rebound hunger following the consumption of reduced calorie foods. The research will also enable us to define a broader research programme to investigate mouth-gut-brain interface that will study in more detail variations between individual responses, and the biological mechanisms behind our behavioural measures (such as gut hormone levels). Knowledge generated will enable better approaches to reduced calorie foods that are more effective at reducing energy intake in the longer term.

We propose a new imaging platform that combines ultra-fast confocal imaging with the the nano-fluidic functionality delivered by an integrated Fluidic Force microscope (FluidFM-UFCLSM). The proposed capability opens a new phase of exploration of biological systems by enabling characterisation of localised biochemical and physiological processes. The proposed capability provides new avenues for specific applications such as new antimicrobial agents, functional genetics and the development of sustainable crops. The unique design of FluidFM-UFCLSM enables accommodating an array of complex biological samples to perform quantitative and predictive characterisation of biofilms, tissues, whole plants, small animals, insects, mucosal membranes, food systems and tissue scaffold hydrogels. The unique feature of FluidFM-UFCLSM is it will enable study of the smallest units of biological organisation such as proteins as well as larger objects such as cells, tissues and organs. The use of FluidFM-UFCLSM cuts across many disciplines and delivers benefits to a broad range of research topics in the areas of biofilm formation, plant science, tissue engineering, food science and cell physiology. Some examples of FluidFM-UFCLSM applications are: 1) Elucidate anti-microbial resistance and the localised mechanisms underpinning quorum sensing 1) Probe interaction between immune cells with lung epithelium as one of the key pathways of Covid-19 pathogenies 2) Uncover the secrets of plant development and mechanical signalling to develop new resistant crops 3) Probe the effect of nutrition on gut microbiome and associated health outcomes 4) Explore new plant-mimetic materials for designing new food-compatible films for environmentally sustainable food production The broader areas of impact will be achieved by supporting emerging areas research that targets the major problems and challenges of food security, improved nutrition, animal and human health, combatting antimicrobial resistance, microbiome research, industrial biotechnology, waste valorisation, sustainable agricultural and synthetic biology.