It has oft been said that, 'if you can't measure it, you can't make it'. Measurement is fundamental to manufacturing technology, and requires specialised and broad knowledge, not only to make a critical measurement, but also to interpret and apply the results appropriately. The old-fashioned way to polish precision lenses and mirrors is to rub them in a controlled manner using a water-slurry of polishing powder with a polishing tool (which might in the later stages be the optician's thumb!). In most applications it is necessary to achieve both an excellent smooth polish free of defects, and a precisely shaped surface (we call it 'surface-form') good to a few millionths of an inch. To achieve this requires many cycles of measurement and polishing. A modern computer controlled polishing machine, such as produced by one of the project-partners Zeeko Ltd, can speed up and control the process, making it more automated and predictable. Nevertheless, repeated cycles of measurement are still needed, because of the underlying complexity at the microscopic level of the physics and chemistry behind polishing. In practice, this usually means de-mounting the lens or mirror from the polishing machine-tool, and moving it to a measurement instrument, which increases production-time and introduces risk of damage. The challenge of measurement becomes acute when trying to manufacture precision surfaces which have complex forms. These include 'aspheres' (surfaces which differ from part of a sphere), and the truly unruly surfaces called 'free-forms' (which may have seemingly random humps and hollows like a Pringle). Today, the technology to polish such complex surfaces in a controlled manner is well ahead of the ability to measure them. It is the measurement part of the cycle which is severely limiting the accuracy that can be achieved, and thwarting the ability of industry to capitalise on the advantages which such surfaces can confer. So why does industry want these complex surfaces? Consider two examples. In optics, complex surfaces provide the designer with more features that can be changed in the computer, when designing a particular lens or mirror. In general, this means that the same job can be done with fewer pieces of glass (lighter, more compact systems), or better performance can be achieved (sharper images). In a completely different field - medicine - artificial knee joints are complex saddle-like forms, and superior quality can increase the joint's life in the patient. To make sense of the increasing need to measure and control complex surfaces requires breadth of knowledge, spanning measurement instrumentation, computer-interfaces, data-analysis, software techniques, sources of errors, and much more. At one extreme, the relationship of measurement to the manufacturing processes is crucial; at the other, a grasp of the demands of the final application is critical to successful manufacturing. This is why technology transfer is the very essence of the proposed project, so that the industrial partners can enhance their own skills in addressing the marketplace, but also so that the scientific community can benefit through enhanced technical capabilities. Technology Transfer as we call it is all about people, and one of the best ways to do it is to address a common problem as a team. The central problem we address is how most effectively to measure complex parts as they are processed on the Zeeko polishing machines. With technology-transfer in view, the project focuses on developing a challenging prototype instrument which will combine two measuring methods in a novel way. The result will be a compact measuring module which will fit into the tool-holder on the Zeeko machines. This will enable a complex part to be measured as a set of overlapping patches, using the machine's 7-axis motion-system to provide the surface-scanning. It remains to take these separate patches and mathematically stitch them together.

In developed economies the manufacture of high added value critical components is rapidly shifting to the design and fabrication of micro and nano structured and freeform surfaces. The market for components possessing these surfaces is huge (the annual turnover is over 75 billion in the UK) and growing by 25% per year (1996-2005) with great investment in the UK, USA, Germany, France and East Asia. The rapidly increasing use of nano scale and ultra-precision structured surfaces is wide ranging and covers optics, hard disks, medical devices and the micro moulding industries that all critically rely on ultra precision surfaces. The scale of the products does not limit the need for the surface precision. The James Webb Space Telescope project for instance requires 1.3 metre size complex freeform surface segmented telescope mirrors with less than 10nm form deviation.Ultra-precision multi-axis machining and micro-fabrication technologies are enabling technologies that allow the designed surfaces to be fabricated with the required sub-micrometer form accuracy and nanometric surface topography. There is however a fundamental limiting factor to manufacture of such surfaces, namely the ability to measure product with high level accuracy, and also on-line.The proposed project attempts to create a novel in/on line surface measurement system, which integrates the essential optical components of an interferometer, such as, light source, optical components, a detector, into a solid state chip device. The key and novel aspect of the research, within the project, is to study and develop techniques to fabricate and integrate optical elements onto the same motherboard chip. The feasibility of building a robust and miniature surface measurement system and applying it to on-line micro and nanoscale surface measurement will then be explored. The proposed project will involve an interdisciplinary team of researchers and industrialists: the Surface Metrology Group at the University of Huddersfield (UoH), the Centre for Integrated Photonics (CIP), instrument manufacturer Taylor Hobson Limited (TH) and Ultra-Precision Surfaces at the OpTIC Technium (OpTIC) in North Wales. The group's combined activities include 'state of the art' capabilities in surface metrology, integrated optics, metrology instruments and ultra-precision surface manufacturing. The aim is to demonstrate a unique and novel technique for micro, nano scale manufacture that represents a step change in the field of surface metrology, integrated optics, nanotechnology, and instrumentation. The inclusion of the partners demonstrates the supply chain required in such systems / the research group (Huddersfield) developing the fundamental measurement system approach, a technology translator and device manufacturer (CIP), a measurement tool manufacturer (Taylor-Hobson) and an end user (OpTIC). Should the project succeed as planned, then there is an excellent chance of downstreaming this approach into commercialisation.CIP is a subcontractor on this project responsible for the delivery of the advanced optoelectronic devices used in the project and the final optoelectronic hybrid chip. CIP - a not for profit organisation - has a track record of working with university groups in this way for the development of advanced components for research. Previous examples being the EPSRC funded projects PRINCE and PORTRAIT where CIP were (and are) responsible for the development of leading edge research devices for telecommunications, terahertz imaging, biophotonics and sensing applications within these projects. The centre provides an open acess R&D facility for industry and universities. The EPSRC have agreed to support the access to CIP for academics by funding full economic costs on individual research grants.

A major challenge in biology is to understand how cells recognize external signals and give appropriate responses. Now that the sequence of the human genome is complete, it is important to assign functions to each gene and to identify the corresponding proteins that control key cellular functions. White and colleagues pioneered the development of microscopy-based methods for the visualization and timelapse measurement of biological processes in single living cells. We have used natural light-emitting proteins from fireflies, jelly fish and fluorescent corals. Synthesis (expression) of these proteins causes mammalian cells to become luminescent (light emitting in the dark) or fluorescent (change the colour of light). By placing the gene that codes for a luminescent protein next to a promoter that controls a gene of interest, we can use luminescence from living cells as a way of measuring when the gene of interest is normally switched on and off. Fluorescent proteins have also been used to genetically label proteins of interest, so that the movement of the protein can be visualized in a living cell. White and colleagues previously used timelapse fluorescence and luminescence microscopy coupled to computer simulations to investigate cell decision making. We discovered that a set of important signalling proteins, called NF-kappaB, move repeatedly into and out of the nucleus of the cell, suggesting that cells may use proteins as timers to encode complex messages (like Morse Code). This was a surprise since the original NF-kappaB protein, p65, was discovered 20 years ago and was thought to act as a simple switch that moves into the nucleus once to activate genes. Only timelapse measurements in single living cells were able to see this. The NF-kappaB system is widely recognised as crucial to the control of important cellular processes including both cell division and cell death. It is implicated as being involved in a variety of diseases, such as cancer and inflammatory disease. We will now develop a substantial systems biology project to study all of the components of this complex system. While the previous work has provided major insights, we now need a far broader range of integrated experimental tools to study it. Also the use of mathematical models to make computer predictions will be critical to help us to visualize how this system works. We will make accurate measurements of the (much larger) set of proteins that are involved in NF-kappaB signalling and the genes that are controlled by these signals. The (very experienced) project team includes bioinformaticians, cell biologists, computer scientists, mathematicians, molecular biologists, microscopists and protein chemists. The project will be managed in a structured and organized way, so that the mathematical modelling can be used to predict and design the biological experiments. A central team of experimental officers will be responsible for coordinating the experiments, data and model storage and communication of information between team members. We will study the numbers of molecules of each of the NF-kappaB proteins in the cell, their stability, chemical states and interactions with each other and with other proteins. We will also study in detail which genes that they bind to and control. We will also aim to understand how single protein molecules acting at single genes can act to control decisions of cell life and death. This multidisciplinary approach is essential in order to understand this complex system. A further aim of the project is to provide training for post-docs and students. In this respect, we will benefit from sponsorship of training courses and symposia by the instrumentation companies Carl Zeiss, Hamamatsu Photonics, Coherent and Nano Imaging Devices. The project will also benefit from ongoing collaborations with Genetix and AstraZeneca

Agriculture underpins European industry with an annual turnover of more than ¤1 trillion and is essential for our survival. As resources dwindle and world populations grow, our demands on agriculture will also increase. As climate changes in the coming decades, current trends suggest that global temperatures will rise. Not only is mean temperature set to change but weather systems are also becoming less predictable: an unprecedented frost this year resulted in a failure of the Californian citrus crop, costing the industry $450 million. The combination of increased demand on agriculture and the changes in global climate and weather extremes represent a major challenge for science in the 21st century. To meet this challenge, we need to know how plants both respond to and protect against temperature changes. The same issues apply to other environmental factors across all biological systems, therefore, understanding this is a major goal for experimental and theoretical scientists. In recent years reductionist science, where biological pathways are studied in isolation, has not identified plant temperature sensors. It also cannot address how temperature effects that cross the many, interacting pathways, which we now know are involved. We take a multi-disciplinary approach and focus our studies on one of the best characterised signalling networks in plants. We will combine expertise from biologists that specialise in molecular and cell biology, plant physiology and climate change; and theoreticians that specialise in statistical, mathematical and computer science approaches to analyse and model biological systems. To provide vital independent expertise and avenues for collaboration we have invited a panel of experts from industry and academia, to meet with us on a yearly basis. We will analyse how temperature influences the interlinked pathways of light, 24-hour clock and cold signalling. We conduct our studies in the model plant Arabidopsis as it offers several advantages: 1. we have already developed the most advanced mathematical model in plant signalling, for a section of our network; 2. our network pathways are already well defined, with many useful tools and resources in Arabidopsis; and 3. the pathways in plants of economic and ecological importance appear to be closely related, so our results can readily be translated to other species. To capture a meaningful view of how temperature-regulated molecular events translate to important physiological traits we will conduct our analysis at molecular, cellular and whole plant levels. Our first task will be to expand our model with the pre-existing knowledge for the rest of our network. We will measure the response of all our network components over a range of temperatures and integrate these data into our preliminary model. This, approach will locate the temperature-sensitive and -tolerant parts of the network in an unbiased fashion: the important point is that the temperature responses that matter will not be caused by single components, but by many acting together. We cannot understand this complexity without computer models. Our models will help inform our experiments, to home in on the molecular mechanisms that control the network's properties. Finally, we will test the role of important network components in controlling agriculturally and ecologically relevant traits in whole plants. In summary, this project will develop the most advanced signalling network model in plants, define network features that permit responsiveness and tolerance, and identify plant temperature sensors. Our work will address fundamental questions in biology and create the knowledge base required to meet the challenge to develop crops better able to withstand a range of climatic conditions. Our multidisciplinary collaboration will also provide training and extension of 'Systems Biology' approaches to universities with no current expertise and to our industrial collaborators.