In order to develop new vaccines, or new ways of delivering vaccines, it is necessary to demonstrate that they provide protection from the disease of interest. One of the most frequently employed ways of doing this is by the use of vaccination challenge studies. In such studies laboratory animals are immunized with the vaccine and then exposed to the disease of interest: if the vaccine is effective then the animals are protected from illness (or at least more protected than animals which did not receive the vaccine). In the case of certain diseases, the number of laboratory animals which are used in these kinds of studies can be reduced by measuring the immune response of the animals following vaccination. In such cases, the immune response can be used to predict how well an animal will be protected from disease, without the need to actually expose it to the disease causing organism. However, in the case of tuberculosis, as well as a number of other important diseases, reliable immune response predictors of vaccination success have eluded identification because there is no single immune response (e.g. antibody production) associated with protection from disease. This project aims to assess whether a recently developed technique called ?RNA sequencing? can be used to address this problem. The immune response to tuberculosis is complicated, and involves the combined action of several different types of cells, which are co-ordinated by protein messenger molecules and protein molecules on the surfaces of cells. In turn, these are controlled by genes, which can be either up-regulated or down-regulated. RNA sequencing allows the degree to which these genes are being up or down-regulated to be measured. Hence it is possible to study the combined immune response of an individual following vaccination, rather than studying specific components. The samples which will be analysed in this study come from badgers vaccinated against tuberculosis. Badgers are known to be susceptible to infection with tuberculosis, and can transmit the disease to cattle. As badgers are legally protected in the United Kingdom, vaccinating them against tuberculosis provides a potentially valuable approach to controlling the disease in cattle. This project aims to identify immune responses in badgers following vaccination which predict how well protected they will be from tuberculosis, using RNA sequencing. Identifying such responses has the potential to reduce the number of animals which need to be used in this kind of research.

The objective of this project is to use reverse genetics to develop better ways of making vaccines that protect against more than one disease (multivalent vaccines). This technology allows us to mutate RNA virus genomes through DNA copies (cDNA) of the RNA genome. The new genome cDNA can then be used to obtain the mutated form of the virus. In these studies we will use an existing vaccine for peste des petits ruminants virus (PPRV), as a vector to deliver antigens from other economically important viruses. PPRV causes a devastating plague in small ruminants and has a severe impact on animal welfare and the economies of many countries in Africa and Asia. In previous studies using this technology with a related virus, rinderpest virus (RPV), we were able to express foreign proteins efficiently in infected cells and to produce effective marker vaccines for RPV as well as identify some of the molecular factors which determine differences in virulence between virus strains. Recently it has been shown that the genome of measles virus (MV), a closely related virus, can be artificially segmented and that cDNAs of these segments can be used in a similar way to the full-length nonsegmented cDNA to rescue viable virus. The segmentation and rescue of PPRV will provide a new way to deliver immunogens from other small ruminant viral pathogens. Work with other nonsegmented negative strand (NNS) viruses has shown that there is a limit to the amount of extra genetic material that can be added to NNS virus genomes before a reduction in virus viability is seen. Segmentation of NNS genome can effectively overcome this limit, as evidenced by the ability of the segmented MV to encode at up to six foreign proteins efficiently. If this is applicable to related viruses then it would increase their coding capacity and enable us to produce multivalent vaccines to simultaneously protect against several economically important diseases of ruminants and increase their cost-effectiveness. Whilst RPV has been virtually eliminated from the globe as a result of a concerted vaccination campaign over the past 20 years, PPRV is a disease emerging in new regions of the world and is now causing great economic losses across much of the developing world as well as on the borders of the European Union. The current live-attenuated vaccines developed for PPRV are safe and highly effective and are, therefore, ideal candidates for use as vaccine vectors that can be tagged to allow differentiation between infected and vaccinated animals. We wish to explore the segmented approach using PPRV as a vector delivery system for multiple antigens from other economically significant viruses such as bluetongue virus (BTV) and Rift Valley Fever virus (RVFV), insect borne pathogens which can infect cattle and sheep, the latter also being able to infect humans. BTV and RVFV were once considered exotic diseases although recently BTV has entered the European Union, having a devastating effect on agriculture. RVFV has the potential to also enter Europe as insect vectors that carry BTV may also competent for RVFV infection. Current use of the PPRV vaccine generates a sterilising immunity that gives lifelong protection against the virus and, for RVFV, a similar response is thought to be generated post vaccination. However, for BTV a number of distinct genetic variants exist which, although diverse, cluster across distinct geographical regions. We wish to develop vaccines that target viruses circulating within a specific areas. Both RVFV and BTV are endemic across much of Asia and Africa and effective vaccination strategies are integral to their control. The three viral diseases targeted in this proposal are in line with the BBSRC's combating diseases of the developing world strategy as well as DFID's long term commitment to improving the sustainability of agriculture in developing countries.

This project will support the implementation of children's rights in Northern Ireland. The UK ratified the United Nations Convention on the Rights of the Child (the CRC) in 1990 and its obligations apply equally across the UK, including the devolved administrations of Scotland, Wales and Northern Ireland. While there have been some legislative developments in other parts of the UK in relation to children's rights, in Northern Ireland this has not been the case. Recent research carried out by Queen's University Belfast on behalf of NICCY highlighted a number of significant barriers to the implementation of children's rights in Northern Ireland and indicated a need for a much more consistent and systematic application of a children's rights framework to policy and practice. The Northern Ireland Commissioner for Children and Young People was established in 2003 under the Commissioner for Children and Young People (Northern Ireland) Order. The principal aim of the Commissioner is to safeguard and promote the rights and best interests of children and young people, including through keeping under review the adequacy and effectiveness of law and practice relating to the rights and welfare of children and young people. This project will take the form of an academic placement within NICCY. The placement will build upon the recommendations of the recent research carried out by Queen's University Belfast. Specifically, the placement fellow will develop a policy briefing on legislative mechanisms for implementing children's rights in Northern Ireland. The policy briefing will: review existing mechanisms and models of children's rights implementation as adopted by other countries; identify the advantages and disadvantages of these approaches, and the challenges experienced in their development; and assess their suitability for implementing children's rights in Northern Ireland. As part of this activity, the placement fellow will organise a workshop inviting policymakers and representatives from local community and voluntary sector organisations, to facilitate the exchange of ideas with respect to legislative measures that could be taken to implement children's rights in Northern Ireland, including the possible content of any Children's Rights Bill. The placement fellow will also work with NICCY to disseminate and publicise the policy briefing with policymakers, community and voluntary organisations and other key stakeholders. The project team will engage directly with key child rights NGOs including Children in Northern Ireland and the Children's Law Centre, and academics through an Advisory Group, which will meet regularly over the lifetime of the project. The project will enable NICCY to draw upon independent academic expertise in an area of identified need, and give the project team the opportunity to positively impact upon the policy and practice in this domain. Ultimately, it is envisaged that the project will lead to more effective implementation of children's rights in Northern Ireland, to the overall benefit of children and young people therein.

Tick-borne diseases cause a significant health burden on both the human and domestic livestock populations within the United Kingdom (UK). This includes the recently detected tick-borne encephalitis virus, a common cause of encephalitis in humans across Europe, and the livestock disease caused by louping ill virus. Both are types of flaviviruses and are closely related, and both are now endemic within the UK. Many questions remain concerning the biology of these viruses and there are key gaps in understanding virus distribution within tick vector populations, fundamental questions on flavivirus virus pathogenesis and a clear lack of serological tests that can distinguish between antibodies to either virus in order to tell which is circulating in the different host species. To address these gaps, the TickTools project aims to conduct a series of studies, each coordinated by one of the project partners. The Animal and Plant Health Agency (APHA) will conduct field surveys for adult ticks from across the UK and determine the microbiological make-up present within each sample, which will identify all viruses and bacteria present. This approach will also capture the genome of each tick that can be used to assess the relationships between tick-populations within the country, which in turn could reveal the interactions between these populations and how ticks, and their pathogens disperse. APHA will support the University of Glasgow Centre for Virus Research (CVR) in establishing a virus infection model to determine the pathogenesis of tick-borne flaviviruses. This will be achieved by comparing the virulent virus with an attenuated virus. This approach will identify potential therapeutic targets for prevention and control of flavivirus infection with the aim of preventing the most severe manifestations of virus infection. From these studies, CVR will supply organ tissue (spleen) to the University of Nottingham (UoN) to support their development of scFv antibodies that can be used to further study both viruses but also have potential as treatments for people or pets that become infected. The UoN will also develop antigen (peptide) panels that will discriminate between serological responses to infection with either TBEV or LIV. Using assays developed by UoN, serological surveillance in both human and animal populations will be possible.

This project addresses a crucial research question that must be answered in the near term is How complicated can, or should, a dynamic electricity tariff be? , such that it is accepted by the public and offers clear enhancements and incentives for reduction in energy demand? The 'can' and 'should' reflect the fact that any ubiquitous technical system is (primarily) designed and implemented by experts, but has to be accepted and operated by non-experts. This project looks at how the information potentially available from smart meters may be exploited to the advantage of both the distribution network operator and the customer. We are looking for the best overall outcome in terms of energy demand reduction, not the best 'engineering solution'. The driving forces towards the need for dynamic tariffs are strong: increased embedded generation, the introduction of plug-in electric vehicles, decreasing national generating capacity, further additions of medium and large scale variable generators, and the prospect of short-term load-shedding by suspending low priority consumption within commercial and domestic. This project aims to discover understanding of the whole interacting system. This project will take account of the smart metering and infrastructure options outlined in the recent Government consulation and response. Using High-Performance Computing to provide a scalable solution to large-scale data management for smart metering is especially timely as it addresses one of the main issues that was raised in the consultation. If, as a nation, we are to lower our overall energy demand, we will have to shift from fossil fuels to less carbon intensive supplies and optimise our energy consumption across all possible sources. This may mean that electricity demand may increase. At the same time, there is an imminent crisis in generating capacity (by whatever means), so we have to make significantly better use of the energy and the assets which make up the infrastructure. The meter is the interface between the consumer and the network operator, so in principle, a smart meter could manage and provide all of the information which describes the state of the network at that point at that time. Increasing data availability will bring benefits to both users and controllers - with detailed knowledge system behaviour in near-to-real-time at the lowest operational level, network operators have a better opportunity to balance the system load, and concurrently offer consumers much enhanced mechanisms for reducing their own power demand.