Oil from seeds forms a major source of nutrition for humans and livestock. It also has many important industrial uses, among them providing an increasingly relevant source of renewable energy (bio-diesel). The rate of oil accumulation in developing seeds is governed predominantly by biosynthesis. However, a number of studies have reported that a significant amount of oil is also turned over during seed development. Blocking this turnover could potentially elevate oil levels by between 5 and 25%, depending on the species and growth conditions. Controlling oil breakdown in seeds requires knowledge of the molecular mechanism, which until recently was completely lacking. This process also occurs after seed germination where it plays a fundamentally important role in providing energy for early seedling growth. I have gained a new insight into the mechanism of oil breakdown by isolating mutants in the model oilseed plant Arabidopsis that are impaired in post-germinative growth. I have discovered that one of these mutants, called sugar-dependent1, has a defect in the enzyme triacylglycerol hydrolase, which catalyses the first step in oil breakdown. The rate of oil breakdown is dramatically slowed in this mutant and as a consequence the developing seeds accumulate significantly more oil. The goals of this proposal are (i) To study how SDP1 is regulated and establish whether oil breakdown can be inhibited during seed development and not following germination. This would allow oil yield to be enhanced with the minimum impact on seedling vigour. (ii) To identify additional structural and regulatory proteins that function with SDP1 to govern the rate of oil breakdown. Disruption of these proteins will be used to block oil breakdown completely and thereby maximize oil accumulation. (iii) To investigate the role of SDP1 in the crop species oilseed rape and determine if oil yield can also be increased by impairing oil turnover. Addressing these objectives will contribute greatly to our fundamental knowledge of the mechanism and regulation of lipolysis, which is major metabolic process that is essential for the life cycle of many plants. The work could also lead to the development of crop plants with a higher oil yield.

Fish oils have been historically associated with health-beneficial properties and over the last few years a large number of scientific studies have demonstrated the benefits of a diet rich in these oils. In particular, some of the fatty acids found in fish oils seem to play a role in preventing heart attacks and other circulatory problems. These fatty acids are the omega-3 long chain polyunsaturated fatty acids (abbreviated to omega-3 LC-PUFAs), and they are now widely viewed as vital constituents of human diet. As well as being able to play a role in preventing diseases, fish oil omega-3 LC-PUFAs are also very important in human growth and development. For example, breast milk contains these fatty acids, and it is for this reason formula (replacement) milks are now enriched in these fats. The primary source of omega-3 LC-PUFAs is fish oils, but unfortunately global fish stocks are now in severe decline (mainly due to decades of over-fishing). This not only represents an ecological crisis, but may also, in the future, severely hamper the availability of fish oils to maintain a healthy diet. Moreover, there are growing concerns about the contamination of current wild fish stocks with pollutants such as heavy metals, plasticizers and dioxins. Therefore, there is an urgent need to find a new sustainable source of these very important fatty acids. One approach that we are undertaking is to try and make fish oils in plants. This requires genetic engineering of a suitable plant (ideally an oilseed), because there are no known examples of higher plants which synthesise omega-3 LC-PUFAs. To carry out this work, the genes which direct the synthesis of omega-3 LC-PUFAs need to be introduced in a plant. These genes come from the tiny microbes (such as algae) which live in the ocean and synthesise omega-3 LC-PUFAs, so the project involves moving these genes into plants, to allow the synthesis of these important fatty acids in a clean and sustainable manner.

Currently, the manufacture of pharmaceuticals, agrochemicals and other fine chemicals relies heavily on synthetic chemical methods, which use deleterious solvents, reagents and catalysts as well as non-renewable petrochemical precursors, which have serious detrimental environmental impact. Consequently, alternative biotechnology based processes are sought for the more economic and environmentally sustainable manufacture of those chemicals that are essential to maintain human health and quality of life. Central to the development of industrial biotechnologies is the availability of new enzymes, with tailored properties, that can be used to catalyse the transformation of renewable precursors into the required products under environmentally benign conditions. To date, industrial applications of enzymes have relied on a limited number of established enzymes, which catalyse a narrow range of transformations. However, recent genome sequencing has led to the discovery of a wider range of enzymes from natural sources. In addition new directed evolution technologies allow the properties of enzymes and even the reactions they catalyse to be altered and optimised for specific processes. Recently we solved the first structure and determined the detailed mechanism of a decarboxylase enzyme (AMDase) that catalyses the loss of carbon dioxide (decarboxylation) from malonic acid derivatives to generate chiral carboxylic acids. In this project, we aim to use these structural and mechanistic insights to develop more powerful decarboxylase enzymes that can provide access to a much wider range of structurally diverse carboxylic acids, which are particularly common intermediates in production of pharmaceuticals, agrochemicals and other products. The new decarboxylase enzymes are also attractive because the substrates can be generated from malonic acid, a natural precursor derived from renewable sources (fermentation). The availability of chiral carboxylic acids, which are single enantiomers (one of two possible stereoisomers that are non-superimposable mirror images) is of critical importance particularly for pharmaceutical production. Typically, enzymes only produce one of the two possible enantiomers, which is problematic if the opposite enantiomer is required. We will therefore use directed evolution technologies to develop enzymes that are enantiocomplementary. In this way, one enzyme can be used to produce one enantiomer (left-handed molecule), whilst another enzyme can produce the opposite enantiomer (right-handed molecule). Along with our industrial partners at BASF, who are the world's largest chemical manufacturers, we will tailor the new enantiocomplementary decarboxylases for production of key pharmaceutical intermediates. This includes chiral carboxylic acids used to manufacture non-steroidal anti-inflammatory drugs (from the ibuprofen family), the antiplatelet agent clopidogrel (the world's second-best selling drug) and captopril which is used to treat cardiac conditions. The family of enzymes to which the decarboxylases belong are known to be promiscuous, and can catalyse a wider range of reactions than decarboxylations, including racemisations and isomerisations. We aim to further explore the promiscuity of this enzyme family, with a view to developing alternative reactions that would also be of industrial importance.

Photovoltaic devices that harvest the energy provided by the sun have great potential as clean, renewable sources of electricity. Despite this, uptake of photovoltaic energy generation has not been strong, largely because devices based on many current technologies are still too expensive. One promising alternative is given by organic-inorganic hybrid cells based on dye-sensitised metal oxide mesoporous electrodes, which are cheaper to produce and have reached power conversion efficiencies of over 11%. However, there remain concerns about the incorporated redox active liquid electrolyte, presenting the possibility of toxic, corrosive chemicals leakage. Recent research into replacing the liquid electrolyte with a solid-state hole-transporter has yielded cells with up to 5% power conversion efficiency. Here we propose a structured research programme that will lead to increases in the power conversion efficiencies of all-solid-state dye-sensitized solar cells (SDSCs) towards that of their electrolyte-containing counterparts. In particular, we will use a new approach in order to establish criteria for optimization of essential parameters such as the nanoscale morphology of the electrodes, the charge-mobility for the hole-transporter and the energetic level arrangement at the interface. The study will combine device measurements with a range of time-resolved spectroscopic investigations to deduce how each change to the system affects individual photophysical processes (such as photo-excited electron transfer) in the material, and how this translates into efficiency of device operation. Work will be based on a careful selection of material components that allow tuning of only one particular property at a time. This combined new approach will not only allow significant improvements to be made to specific SDSC designs, but also deliver a more general framework for the exact requirements of successful optimization approaches.

Many important questions and challenges in process systems design, operation and control can be typically posed as nonlinear optimization problems. To date, most optimal decision making tools for such problems are mainly based on deterministic mathematical models, where all parameter values in the model are assumed to be known precisely. In practice, however, mathematical models are merely approximate descriptions of the real system, and parameters such as future demands, prices, equipment wearout and process conditions are subject to significant uncertainty. It has been frequently shown that disregarding such uncertainty can lead to severe performance losses, increased costs, and energy/environmental penalties. We propose to develop robust, local and global optimization methods for the efficient solution of such nonlinear optimization problems in the presence of uncertainties. Depending on their nature, uncertainties can be accounted for in a static/proactive or reactive way. Two important industrial applications will be investigated and the developed methods will be applied for the integrated design, optimization and control of process systems under uncertainty.