The highly competitive grass weed, Alopecurus myosuroides (black-grass) is prone to the evolution of resistance to herbicides. The extent of evolved herbicide resistance is currently greatest in the UK and France where documented cases of resistance to acetyl co-enzyme A carboxylase (ACCase) -inhibiting and acetolactate synthase (ALS) -inhibiting herbicides are common and widespread. More recently, the species is rapidly expanding its range northwards and eastwards and reports of resistance are increasing in Germany and other countries. At the same time, current changes to EU pesticide registration are reducing the number of herbicide modes of action available for black-grass control, making it probable that resistance to remaining modes of action will be an even greater issue in future. These increases in the prevalence and risk of herbicide resistance must drive agrichemical companies, farmers and advisers towards the provision of more sustainable herbicide use strategies and greater adoption of integrated weed management. Demo-genetic models can combine knowledge of the demography and life cycle of black-grass with our current understanding of the genetic basis of herbicide resistance to examine the influence of various management practices on the evolution and spread of herbicide resistance. These models have been developed previously by the academic supervisor for other weed species. This project will build upon and enhance these approaches by using the extensive database of black-grass resistance cases that Bayer CropScience has been collating since 2008. For each suspected resistant black-grass population that is sent to Bayer, an extensive suite of laboratory and glasshouse tests are performed to determine the extent of resistance, as well its genetic and mechanistic basis. This provides a unique dataset documenting the extent and distribution of different resistance mechanisms across Europe as well as information on the frequency and phenotypic consequences (resistance profile) of various resistance-endowing point mutations. This dataset is even more compelling as it includes a field management history for each location from which black-grass is sampled, providing the opportunity to relate the extent and mechanism of resistance to past management. A major limitation of previous models of herbicide resistance evolution has been the lack of data on the relative frequency of various resistance mechanisms and mutations and it is envisaged that major advances in resistance management can be achieved by combining this data into a modelling format. The developed model will be able to simultaneously simulate evolution of resistance via multiple resistance mechanisms and knowledge of the relative frequencies of mechanisms and mutations together with their resistance profile will be used to explore management strategies to reduce risks of resistance evolution. In the first instance, evolution of resistance will be simulated in individual fields. However, a longer term aim of the project will be to consider evolution of resistance on a landscape scale by simulating black-grass populations in a network of fields with contrasting management and with gene flow between the fields. In addition to modelling, the student will also conduct an annual random survey of black-grass populations from the UK. The extent of resistance in these populations will be determined in glasshouse assays at the University of Warwick. Further experiments will be conducted to examine the fitness consequences of resistance in these populations and this information will be used to help develop the demo-genetic model. During each year, the student will spend a 2-3 month period at the Bayer Crop Science Integrated Weed Management and Herbicide Resistance diagnostics laboratory in Frankfurt. During this time they will perform a suite of molecular physiological assays to determine the resistance mechanisms present in the UK collected populations.

Neonicotinoids represent the fastest-growing class of insecticides introduced for pest management since the commercialisation of pyrethroids. Their sales worldwide are already estimated to exceed one billion US dollars per year. These novel, safe and highly effective compounds provide a invaluable respite from problems of pest resistance to earlier-used chemicals, but are themselves very vulnerable to appearance of new resistance mechanisms. Widespread establishment of neonicotinoid resistance would severely compromise the environmental and economic sustainability of crop protection strategies in many parts of the world including the UK. The brown rice planthopper (Nilaparvata lugens) and the tobacco whitefly (Bemisia tabaci) are two of the relatively few species to have developed strong neonicotinoid resistance to date. Such species serve as ideal models for analysing the underlying mechanisms and their practical implications, and for forewarning of potential problems in a wider range of pest species. Little is still known about the mechanisms that could confer protection from neonicotinoids. However, in N. lugens we have identified a mutation in the nicotinic acetylcholine receptor (nAChR), the protein in the insect nervous system targeted by neonicotinoids, which greatly reduces binding between insecticides and the receptor and confers substantially reduced susceptibility in whole-organism bioassays. Since target-site resistance mutations for other insecticide classes have often proved to be identical across species, results from planthoppers are likely to be transferable to other major targets of neonicotinoids. This project will exploit established, international monitoring networks to obtain samples of N. lugens, B. tabaci, Myzus persicae (peach-potato aphid) and Ctenocephalides felis (cat flea) from areas of intensive neonicotinoid use for phenotypic characterisation of resistance and molecular characterisation of possible target-site resistance mechanisms. The latter will include membrane binding studies and sequencing of nAChR genes to detect mutations putatively associated with reduced binding, and expression studies to investigate such an association. Based on these findings we will develop and validate high throughput DNA-based assays for diagnosing resistance mutations in individual insects in order to monitor their incidence and aid resistance management strategies.

This application requests funds to continue and develop the EngD in Formulation Engineering which has been supported by EPSRC since 2001. The EngD was developed in response to the needs of the modern process industries. Classical process engineering is concerned with processing materials, such as petrochemicals, which can be described in thermodynamic terms. However, modern process engineering is increasingly concerned with production of materials whose structure (micro- to nano- scale) and chemistry is complex and a function of the processing it has received. For optimal performance the process must be designed concurrently with the product, as to extract commercial value requires reliable and rapid scale-up. Examples include: foods, pharmaceuticals, paints, catalysts and fuel cell electrodes, structured ceramics, thin films, cosmetics, detergents and agrochemicals. In all of these, material formulation and microstructure controls the physical and chemical properties that are essential to its function. The Centre exploits the fact that the science within these industry sectors is common and built around designing processes to generate microstructure:(i) To optimise molecular delivery: for example, there is commonality between food, personal care and pharmaceuticals; in all of these sectors molecular delivery of actives is critical (in foods, to the stomach and GI tract, to the skin in personal care, throughout the body for the pharmaceutical industry);(ii) To control structure in-process: for example, fuel cell elements and catalysts require a structure which allows efficient passage of critical molecules over wide ranges of temperature and pressure; identical issues are faced in the manufacture of structured ceramics for investment casting;(iii) Using processes with appropriate scale and defined scale-up rules: the need is to create processes which can efficiently manufacture these products with minimal waste and changeover losses.The research issues that affect widely different industry sectors are thus the same: the need is to understand the processing that results in optimal nano- to microstructure and thus optimal effect. Products are either structured solids, soft solids or structured liquids, with properties that are highly process-dependent. To make these products efficiently requires combined understanding of their chemistry, processing and materials science. Research in this area has direct industrial benefits because of the sensitivity of the products to their processes of manufacture, and is of significant value to the UK as demonstrated by our current industry base, which includes a significant number of FMCG (Fast Moving Consumer Goods) companies in which product innovation is especially rapid and consumer focused. The need for, and the added value of, the EngD Centre is thus to bring together different industries and industry sectors to form a coherent underpinning research programme in Formulation Engineering. We have letters of support from 19 companies including (i) large companies who have already shown their support through multiple REs (including Unilever, P+G, Rolls Royce, Imerys, Johnson Matthey, Cadbury and Boots), (ii) companies new to the Centre who have been attracted by our research skills and industry base (including Bayer, Akzo Nobel, BASF, Fonterra (NZ), Bristol Myers Squibb and Pepsico).