Food and healthcare are the foundations on which our current quality of life is built. The pressure on these resources will only increase as the UK population ages, the global population reaches 9 billion in 2050 and the worst effects of climate change begin to manifest. Now more than ever, new medicines and agrochemicals will be vital in combating the growing and evolving threats that face society. A major challenge to the development of new medicines and agrochemicals is the high attrition rate of the candidate molecules being investigated, which drives up the financial cost, environmental impact and time associated with bringing a new product to market. Methods that allow rapid cost- and resource efficient preparation of desirable candidate molecules are therefore extremely valuable. This programme will deliver a suite of synthesis methods to streamline the discovery and development of the next generation of agrochemicals and pharmaceuticals. Building on our recent discovery, we will develop new ways of making valuable molecular architectures while minimising the number of chemical operations required and avoiding the use of toxic or precious elements. By working in close collaboration with leading innovators in crop protection (Syngenta) and human healthcare (AstraZeneca, Pfizer and Carbometrics), we will ensure that our methods will be of direct and immediate benefit. We will also seek to make the reagents we develop commercially available, thus further enabling the rapid and barrierless uptake of our methods.

Doctoral Training Partnerships: a range of postgraduate training is funded by the Research Councils. For information on current funding routes, see the common terminology at https://www.ukri.org/apply-for-funding/how-we-fund-studentships/. Training grants may be to one organisation or to a consortia of research organisations. This portal will show the lead organisation only.

Macrophages are large white blood cells that are the first line of defense against pathogens, but also contribute to much of the pathology of infectious and inflammatory disease. Macrophages are also the bodies cellular waste disposal system, and they are needed for wound healing and for many aspects of normal development. Chickens are of interest because they are an economically important livestock species, they are tractable model in which to study development, and they are vectors for diseases that can affect humans including bacteria that cause food poisoning and avian influenza. This project aims to understand how the production of macrophages is controlled in birds and the function of macrophages in embryonic development. Our hypothesis is that two growth factors, macrophage colony-stimulating factor (CSF-1) and interleukin 34 (IL-34) act through a common receptor (the CSF-1 receptor) to promote the production, migration and function of macrophages in an embryo. In turn, the macrophages are needed for the normal process of organ formation and overall growth in the embryo. To address this hypothesis, we propose to make transgenic animals in which all of the macrophages are tagged with a fluorescent transgene so we can monitor when they appear and how they move about in the embryo. We will make the two growth factors as recombinant proteins, and make antibodies that prevent their actions. And finally, we will test the hypothesis by introducing the factors, or antibodies, into the developing embryo in the egg, to see whether macrophage production or location can be altered, and whether this changes the course of normal development. These are experiments that cannot be done easily in mammals, because the embryo cannot be access in the uterus. If our hypothesis is correct, we will identify candidate modulators of chicken immunity and growth, and also gain an insight into normal development that might be relevant to understanding human pregnancy and developmental defects.

OVERVIEW OF RESEARCH AREA Analytical science is key to the success of any fundamental or applied science research programme, and underpins industrial progress and production in a wide range of areas in which the UK is traditionally strong but where it faces increasing challenges globally. Warwick has an extensive track record both in the highest quality student training through CDTs and in creative instrumental and theoretical analytical science, which forms the background to this proposal for a Molecular Analytical Science Centre (MASC). MASC will focus on developing and applying molecular analytical science methods to problems in 6 themes 1. Measurement, sensing, and extraction in complex matrices 2. Advanced quantitative analysis 3. Molecular structure and stability in complex systems 4. New techniques for Quality by Design in pharmaceutical, biopharmaceutical, agri-science, personal care 5. Characterising and exploiting functional biomolecular assemblies 6. Analytical science for optimising and understanding dynamics in complex systems NEED FOR THE DOCTORAL SCIENTISTS THAT MASC WILL PRODUCE Many reports can be quoted to support the national importance of high quality cross-discipline molecular analytical science training. For example: * The "Health of disciplines: annual report 2008 to the UK research base funders' forum" reported a shortage in physical and analytical scientists as well as shortages in statistics/mathematics and biotechnology. * The 2009 "International Review of UK Chemistry Research" stated that bioanalytical research in the UK is internationally recognised and well-placed to tackle society's greatest challenges, emphasising the continued importance of this area. * A 2006 report for the RSC "Analytical and Measurement Sciences Platform Knowledge Transfer Plan - Survey Findings" noted that "not only are the analytical and measurement sciences extremely diverse and far-reaching in their nature but they are also a massive economic activity in [their] own right. ... analytical sector has £7bn turnover and employs 200,000 people". A driver for this CDT proposal is that the need is not simply for training in existing techniques but also for developing new techniques that will allow us to solve currently open challenges (e.g. the difficulty of proving that a potential generic biopharmaceutical is indeed 'biosimilar'). The Warwick analytical science community embraces the challenge of technique development, as evidenced by a track record in novel instrument and theoretical method development and application. APPROACH TO BE ADOPTED BY MASC The new CDT will benefit from the well-established cross-discipline cohort-based training culture, developed and refined over the 10-year life of the MOAC DTC and the long-running Warwick analytical science MSc programmes, and will be embedded in the research community created by the RCUK Science and Innovation funding that formed the virtual Warwick Centre for Analytical Science in 2008. The MASC students will undertake a cross-discipline MSc programme in year 1, concluding with 2 mini research projects in different disciplines, including both theoretical and experimental research. In years 2-4 they will perform a multi-disciplinary, multi-sector analytical science PhD research project, at a world-leading level, complemented by transferable skills training. Each project will involve technique development and application, with integrated industrial involvement. Students will enjoy the benefit of opportunities during both MSc and PhD to work in an industrial environment and also to experience an international laboratory to enhance their understanding of the scientific process in different contexts. The international secondments will either be to strategic partners of Warwick or to targeted collaborators of the supervisors.

The overall aim of this project is to attenuate the pathogenicity of infectious bronchitis virus (IBV) of poultry in a non-reversible way, whilst maintaining immunogenicity for both vaccination of chickens and for in ovo application. Control of infectious diseases and a reduction in the use of therapeutic antibiotics are two major challenges faced by the UK poultry industry. The avian coronavirus, IBV, is a highly contagious poultry pathogen prevalent in all types of poultry flocks worldwide. IBV is the causal agent of infectious bronchitis (IB) and continues to be responsible for economic loss, welfare problems in chickens and a potential risk to food security. IBV preferentially causes respiratory disease, but can also infect other organs such as the kidneys (resulting in kidney disease) or the reproductive tract (resulting in loss of egg production and/or egg quality). IBV has been reported to be responsible for more economic loss to the UK poultry industry than any other infectious disease. Although live attenuated vaccines and inactivated vaccines are universally used in the control of IBV, the protection gained by use of vaccination can be lost either due to vaccine breakdown or the introduction of a new IBV serotype that is not related to the vaccine used, posing a risk to the poultry industry. It is important that new and safer vaccines are developed for the control of IBV. This proposal seeks to develop an infectious clone system for the generation of rationally attenuated IBV vaccines, identifying two spatially distant regions of the genome that can be modified for attenuation. The project is divided into four main objectives:- 1) To produce an IBV reverse genetics system based on the pathogenic M41 strain of IBV. 2) To remove the M41 accessory non-structural genes to identify whether they play a role in pathogenicity. 3) To study the role of the M41 essential (replicase) non-structural protein genes in pathogenicity. 4) To investigate the attenuation of IBV for in ovo vaccination. This highly innovative project will be carried out by the coronavirus research group at the Institute for Animal Health, Compton which has the necessary IBV reverse genetics technology and the animal facilities to test rIBVs in chickens. The submission is in direct response to research requirements identified and agreed by the Poultry Research Committee at their meeting on the 17th November 2008. Expected benefits to the food chain: Relaxation of IBV vaccination strategies or the breakdown of vaccination, due to new IBV strains, would have a profound and devastating affect on the UK poultry industry in terms of bird welfare and production costs, with associated risks to food security. This work will pave the way for new rationally modified and safer vaccines, as they will be less likely to revert. A further expected benefit from the development of safer vaccines, is a reduction in the amount of antibiotics used to counteract secondary bacterial infections associated with IB.