• UK Research and Innovation close
• 2018 close

Biology is complex; cells are made up of 1000s of proteins, a similar number of metabolites and tens of thousands of genes. A goal of biological research is to understand how this complexity brings about the functions of life. One way to achieve this goal is to understanding the connections between the 1000s of components that make up cells. Measuring the connections between all the components is challenging, particularly because cells are dynamical systems that are constantly changing. Accurate descriptions of the dynamical network interactions that take place in a cell are required to make the advances required for improved crops for food security and new medicines. We have adapted a new tool set from Engineering to describe biological networks in a mathematical form. We make models of each of the connections which are used to predict how the system will change over time, which is very useful in discovering how cells respond to signals such as changes in temperature, hormones or drugs. Our new mathematical tool set allows researchers to identify and quantify the changes in a biological network, which can lead to the discovery of the gene(s) or pathways that are involved in responses to stresses or drugs and might underlie disease. Our new mathematical tool set will have wide utility in understanding a wide range of cellular systems, from the effects of drugs in humans to the response of a crop plant to environmental changes or attack by pests. Our development of a tool that measures how biological networks change is important for understanding biology, curing disease and improving crop plants to provide enhanced food security. We propose to develop this so called Nu gap analysis as a practical tool for biologists. In our implementation, we identify and describe connections in biological systems using simple liner models. The Nu gap measures the difference between the mathematical descriptions of the connections obtained in different conditions, such as following a response to a drug, or an environmental stress. To develop the Nu gap as a practical tool we will undertake a research programme that increases with complexity over time. This will permit rigorous testing, development and deployment of Nu gap analyses. First, we will perform theoretical analyses of the Nu gap on models derived from fabricated datasets designed specifically to assess the strengths and limitations of the Nu gap. This will inform as to where application of the toolset would be best, and conversely the situations where the Nu gap might be less informative. Having developed good theoretical understanding of the system, we will apply the Nu gap to real world data obtained by our laboratories. We will begin using data describing the circadian regulation of gene expression in the model plant Arabidopsis. A major goal will be to investigate the effect of a pharmacological and a genetic perturbation to the circadian system. Both profoundly affect the functioning of the circadian clock, but the mechanisms by which these affect the circadian clock is uncertain. We will move from investigating the fundamental properties of the circadian clock in the model plant Arabidopsis to using linear modelling and Nu gap analyses to describe the circadian clock in a major crop, barley. The circadian clock regulates many important agronomic traits such as flowering time, seed set and cold tolerance. Our studies have the potential to inform breeders of useful gene targets. Recognising that biological systems are more than a series of interactions between genetic components we will extend our analysis to incorporate the physiology of the cell, such as changes in the concentration of calcium in the cytosol, which act as key regulators of signalling in stressful conditions.

Dairy Farmers need to detect Johnne's Disease (JD) or ParaTuberculosis (pTB), more efficiently and reliably to reduce economic loss. JD is a bacterial infection affecting both dairy and beef cattle and impacts upon productivity and profitability; its incidence is cited at between 30-80% in some literature. The impact on the UK industry is between £5 and £20m pa. Internationally, taking the USA as a baseline, the impact is £130m. The aim of this project is to develop a detector that is specific to JD to give the farmer and the veterinarian rapid, easy diagnosis. This system is based on an instrument that samples the air and analyses the atmosphere on farm for a unique mix of Volatile Organic Compounds (VOCs) which indicates the biochemistry of the JD organism. Any change in the VOC mixture to include these VOCs, will provide a diagnosis to JD upon which the Farmer and Veterinarian can make informed decisions. It is envisioned that air samples of faecal matter will be taken from cows about to calf -- allowing the farmer to separate out infected; uninfected and carrier cows and then keeping the uninfected new born calves with the uninfected animals. The reduction in JD would have an impact of herd animal welfare and productivity (milk and meat) and contribute to a more sustainable UK diary industry. This project will include experimental work showing that the concept works and will comprise the selection of JD specific sensors from existing arrays of sensors at Robo and then to carry out 4 months of testing (5 data points) on two farms. This work is expected to substantiate the results of an earlier privately funded "look/see" short project. The second phase will involve evaluating the market for this type of instrument -- identifying the actual need and format of what is needed and evaluating the market in the UK and globally.

Abstracts are not currently available in GtR for all funded research. This is normally because the abstract was not required at the time of proposal submission, but may be because it included sensitive information such as personal details.

Dealing with the consequences of weather related phenomena is an age-old problem. We have made great advances in predicting the weather, but we have made little progress in turning the outputs of these forecasts into actionable information that can help us manage their consequences. The winter storms of 2013/14 and 2014/15 demonstrated that our electrical distribution networks are not only vulnerable to strong winds, but their failure severely impacts on communities. This project will develop and test a new form of weather forecasting, which we term "consequence forecasts". These forecasts are essentially the same as traditional weather forecasts, however, they give a probabilistic assessment of the likely impacts and consequences of weather rather than just predicting the intensity of a weather variable. In this research will make forecasts of the number and location of electricity faults, provided via heat maps, and the number of customers without power. Keywords: wind storm, resilience, electricity infrastructure, natural hazard, consequence forecasts, weather forecasts Stakeholders: Western Power Distribution, National Grid, Energy Networks Association, Met Office, Electricity Consumers

Location and sensing are two important components for Connected and Autonomous Vehicles (CAVs). Sensing techniques using LiDAR, camera, radar have limitations when driving environments change due to bad weather conditions. The mass-market location techniques utilising GNSS, dead reckoning are currently unable to meet the required CAV location performance such as accuracy, availability, robustness. RECAPD will focus on the R&D of affordable new location solutions through identification of location issues on a mix of UK roads using defined CAV location parameters as major indicators. An advanced survey vehicle capable of delivering high-rate centimetre positioning accuracy will be utilised to produce "ground truth" trajectories for assessing the performance of different combinations of potential CAV location sensors. A new CAV location platform that is empowered with the latest processing engine capable of smartly switching among different location solutions according to CAV environments will be developed. It will use the existing national geospatial infrastructure, GNSS carrier-phase signals, inertial data, embedded low-cost beacons (RFID), etc., for the provision of a ubiquitous location solution. The consortium will also work with RECAPD end users for its market opportunities.

This FRL project is concerned with how rising immigration and increasing ethnic diversity affect social cohesion. The UK is currently undergoing a significant demographic shift in the ethnic composition of its populace, with the proportion of non-White British rising from 13% to 20% between 2001 and 2011. Across academic, governmental and public spheres, concerns are being articulated that this growing diversity poses a threat to: residential community cohesion (undermining trust and connectivity between neighbours); wider, societal cohesion (leading to civic disengagement, declining trust in strangers and lower support for welfare policies); and inter-group cohesion (cultivating inter-ethnic tensions, and driving support for far-right organisations). When even conservative estimates predict this trend will only increase, understanding if, how and why ethnic diversity affects social cohesion, and what can be done to ameliorate any pejorative effects, is of paramount importance to the maintenance of a cohesive, harmonious society. Yet, significant gaps remain in our understanding of how of ethnic diversity affects social cohesion. Firstly, much of the current research focuses on how being exposed to diversity within one's residential community affects social cohesion. However, the community is just one site at which individuals come into contact with other ethnic groups. In places like schools, universities, workplaces, volunteering groups, individuals are being exposed to diverse environments everyday. However, how levels of diversity in these places affect social cohesion is largely unknown. This is an important omission given that individuals are actually more likely to encounter diversity in these places than in their neighbourhoods. Secondly, most research assumes that as diversity within an adult's neighbourhood increases, their social cohesion will shift accordingly. However, how adults respond to ethnically diverse environments is likely influenced by all kinds of experiences throughout their lives, such as the attitudes of their parents, the diversity of their schools, and how diverse the neighbourhoods were they grew up in. To understand how diversity affects social cohesion we therefore also need to know what individuals' experiences of ethnic diversity have been over their entire lives. The primary aim of this research is therefore to try and create a much fuller picture of how ethnic diversity affects social cohesion by: firstly, looking at how coming into contact with other groups in schools, workplaces, or civic groups, along with neighbourhoods, affects cohesion; and secondly, how experiences of diversity over one's whole life affects cohesion. Only with this more complete picture of the complex social worlds of individuals can we hope to understand the effect of diversity on social cohesion. However, if we do find that increasing diversity, in certain places, at certain points over an individual's life, can harm social cohesion, then we need to know 'what works' to ameliorate such frictions. This research will therefore investigate how interventions, such as intercultural education, workplace diversity training, national multiculturalism policies, and ethnic mixing programs for adolescents can help alleviate any pressures of increasing diversity. Key to this endeavour will be an analysis of one of the current government's key integration policies: the National Citizen Service.

Young's famous double-slit experiment of 1803 demonstrated that light behaves as a wave. The light emerging from the slits has a characteristic intensity pattern originating from constructive and destructive interference. Later it was found that when single particles (photons or even molecules) pass through a double slit they produce similar interference patterns; this experiment became the key piece of evidence for wave-particle duality. A Mach-Zender interferometer is similar to Young's double-slit setup, except that light is split into two routes using mirrors. When the light is recombined, constructive or destructive interference occurs, depending on the difference in the phase of the light from the two routes. Subtle differences in the path-length, or refractive index, can easily be detected, because they determine the phase difference, and thus they control the interference. This project aims to synthesise and test a "molecular Mach-Zender interferometer" consisting of a molecule with two charge-transport paths; interference between the two transmission channels controls whether the whole system is conductive (in phase) or non-conductive (out of phase). Thus these molecules are expected to be sensitive to magnetic or electric fields which can change the relative phases of the two channels. Furthermore quantum interference effects tend to produce sharp changes in transmission with electron energy, which can result in strong thermoelectric effects. This project is concerned with exploring fundamental principles, but in the long term, this research has the potential to generate commercially disruptive technologies, such as thermoelectric devices for scavenging thermal energy, and transistors with reduced power requirements, abrupt switching and small footprints. This project if a thoroughly integrated collaboration of three research groups focusing on (1) Oxford: design and synthesis of molecular structures, (2) Liverpool: testing of single molecule conductance and thermopower, and (3) Lancaster: theory and computational simulation, to guide the interpretation of the experimental data, and the design of new molecular structures. At present there exists a no-man's land between the 15-nm length scale accessible to top-down technologies, such as electron-beam lithography, and bottom-up technologies such as chemical synthesis. The molecules investigated in this project are 3 nm across, but can be increased in size up to around 10 nm. This project is therefore a significant step towards bridging this crucial technology-scale gap, at the limit of Moore's law.

The epidermis is the outer covering of the skin and plays an essential role in protecting our bodies from bacteria and other pathogens. It is made up of multiple layers of cells that are stacked on top of one another. The deepest cell layer, furthest from the skin surface, contains stem cells. Their role is to divide throughout our lives to make more cells that subsequently mature as they move through the upper cell layers. The most mature cells are specialised to form a protective barrier on the skin surface. If a tiny piece of skin is removed from the body and taken to the laboratory, it is possible to grow sheets of epidermis that have similar properties to normal epidermis and indeed these sheets can be used to repair burns and other types of skin wound. One interesting feature of human epidermis is that the stem cells are clustered in specific positions in the basal cell layer, which correlate with natural undulations in the boundary between the epidermis and the underlying connective tissue. As we age the undulations become much less pronounced, but in contrast in some common skin diseases such as psoriasis the undulations become more prominent. We would like to understand why the stem cells are clustered in this way and whether the size of the undulations affects their behaviour. To investigate this we will grow human epidermal cells on special surfaces made out of artificial materials, such as the rubbery substance used as bath sealant, that recreate the undulations. We will measure whether cells in different positions on these surfaces are more likely to remain as stem cells or to leave the basal layer and mature. We will investigate whether on substrates that resemble aged skin the cells show an altered ability to divide and mature. We will discover how the substrates direct the stem cells to behave by identifying the signalling events that take place inside the stem cells. We will also find out whether we can over-ride the effects of the substrates by artificially stimulating changes in gene expression inside the cells. The outcome of the project will be to explain, for the first time, why stem cells lie in specific locations in human epidermis and whether the information provided by their location contributes to the changes in the epidermis that are linked to skin ageing.

This project will develop an autonomous scout rover system, for scanning and mapping of a nuclear environment as a part of decommissioning effort. The scout rover is an intelligent autonomous machine capable of conducting operations without human interaction, with the long term goal of making decommissioning of nuclear sites safer and quicker. The innovative robotic system will map otherwise inaccessible, cluttered nuclear environments providing vital information for subsequent safety-critical operations. It's autonomy will allow it to perform frequent, repeat inspections of a hazardous environment inaccessible to a human operator allowing hazardous areas to be routinely monitored - reducing the risk caused by nuclear plants awaiting decommissioning. This project combines OC Robotics' demonstrated experience in accessing and operating in confined and hazardous environments with Airbus Defence and Space's cutting-edge expertise in autonomous navigation, originally developed for the European Space Agency's ExoMars 2020 Rover Mission.

Since their discovery in 1967, viruses in the Filoviridae family have caused over 50 outbreaks, of which the last one was the devastating epidemic in West Africa during 2013-16. They cause hemorrhagic fevers in humans and non-human primates with 90% fatality rates and there is no licensed drug or vaccine. This family includes 5 distinct species in the Ebolavirus genus: Ebola (EBOV), Sudan (SUDV), Reston (RESTV), Tai Forest (TAFV), and Bundibugyo (BDBV) viruses; 2 viruses in the Marburg-virus genus: Marburg (MARV) and Ravn (RAVV) viruses; and 1 virus species in the Cuevavirus genus: Lloviu virus (LLOV). To date, most vaccine efforts focus on induction of neutralizing antibodies against EBOV, and also SUDV or MARV. While there is a high degree of conservation within one species, so that, for example, antibody responses to EBOV vaccine would likely cross-react with other EBOV outbreaks, protection against other filoviruses will be very low. Furthermore, future outbreaks may result not only from re-emergence of a virus of a rare species, but also of a completely new, as yet unencountered species. We have designed a vaccine designated FILOcepX with the aim to protect against all filoviruses (Theiler et al. Sci Rep 2016, 6:33987). Our vaccine focuses on induction of effective killer T cells targeting the 4 most conserved protein regions among the entire known Filoviridae family. Because there is a remaining diversity even within conserved regions, the vaccine optimizes the match to all known species by employing computed bi-valent epigraphs (a pair of proteins) used as the vaccine immunogens (cep for Conserved EPigraphs). The two epigraphs complement each other, are always used together and are delivered by safe common cold-like adenovirus and smallpox-like vaccines in a simple, in humans proven highly immunogenic regimen. The T-cell strategy is supported by published protection of macaques against challenge with homologous EBOV challenge through vaccine-induced killer T cells. In preliminary experiments in two strains of mice, research-grade FILOcepX vaccines induced killer T cells recognizing many virus regions. Achieving the aims of Stage I will demonstrate the technical feasibility of our solution, provide a proof-of-concept protection against 2 distant viruses EBOV and MARV in macaques and indicate correlates of T-cell protection for future confirmation to inform licensure, and prepare vaccines for manufacture for human use. If invited, Stage II of the Innovation UK will evaluate the vaccine safety and immunogenicity in a small phase 1 clinical trial in Oxford adults. Post Innovation UK, strong and broad immunogenicity in humans supported by protection against two viruses in macaques may lead to a phase 2 trial in most at-risk human populations. Since phase 3 efficacy trial is not likely to be feasible, licensure may proceed through alternative regulatory pathway based on macaque correlates of protection and human phase 2a safety and immunogeni-city. Licenced vaccine would have multiple uses ranging from generation of vaccine stockpiles for containment of future outbreaks, elimination of the 2013 outbreak remnants, provision of long-term protection in high risk popula-tions to saving highly endangered western gorillas. Potential funders would involve international development agen-cies, the World Bank, philanthropies, defense funds, national governments in risk countries or large vaccine Pharmas.