The molecules that make up the cells of biological organisms do not function in isolation but do so by interacting with other molecules. Cells thus consist of a complex network of interacting molecules. Because the behaviour of an individual molecule is influenced not only by its own properties but also by those of interacting molecules, networks display emergent properties - that is the behaviour of the network as a whole cannot be simply predicted from the properties of its components in isolation. One way of getting to grips with network behaviour is to construct mathematical models that allow network parameters to be computed. This proposal aims to generate a mathematical model that will provide insight into the metabolic network of the model plant species, Arabidopsis thaliana. Metabolism is one of the best described and most studied of all biological networks and yet our understanding of the behaviour of metabolism as a whole remains rather limited. A mathematical model will not only provide new insight into fundamental aspects of control of the plant metabolic network, but it will also be a useful tool to allow predictions to be made about the best way to manipulate the flow of metabolic intermediates. Such metabolic engineering is an important part of attempts to generate new varieties of crop plants that are better equipped to deal with challenges imposed by a changing global climate and the requirements for increased yield.
The Prize Papers are a vast, unique and serendipitous collection held by The National Archives (TNA): time-capsules of daily life in the Early Modern period referencing people from diverse social and cultural backgrounds across the globe. The collection is the result of prize-taking (or the legal capturing of enemy ships) by English privateers and warships during the various European wars between 1652 and 1815. To claim a legal capture and distinguish themselves from mere pirates, seafarers had to confiscate every scrap of paper aboard and take it to the High Court of Admiralty in London, which over the centuries accumulated a huge archive of undelivered letters, trade and maritime documents, colonial administration papers, notebooks and travel journals. Furthermore, the collection holds a range of artefacts, including small objects enclosed in letters (jewellery, buttons, ribbons, embroidered fabrics) which offer a unique opportunity for materiality research and public engagement. We propose a project that uses TNA's CapCo-funded equipment to develop innovative ways of analysing the material make-up of objects in the Prize Papers collection, to better understand their production and use and to support their conservation and preservation. Critically, we propose approaching this task through engagement with communities with a connection to the cultural origins of the objects under investigation. The project will focus on a captivating object as a case study: the wallet of Jan Bekker Teerlink, the supercargo on the Prussian ship Henriette returning from China to Europe with a cargo of tea, which was captured en route off the Dutch coast on 31 May 1803. The contents of his wallet include notes in Dutch and Chinese, a lock of dark hair, seeds from South Africa and a set of vividly dyed samples of Chinese silk and Indian chintz. Researchers in Heritage Science and Conservation will develop, test and apply non/micro-invasive methods to analyse the textile samples using the analytical and imaging suite that include CapCo-funded instruments (TNA's multispectral imaging system and Raman microscope, Victoria and Albert Museum's (VAM) Hirox 3D digital microscope). With the support and expertise of our partner network, we hope to gain insight into the production context of the textiles, the condition of the substrate and dyes, and their vulnerability to light and other environmental factors. Comparative studies of the patterns and materials of Chinese and Indian garments from the same period held in other collections (such as the VAM) will follow, in an attempt to contextualise the fabric samples found in the Prize Papers. The project will also consolidate beneficial collaborations between TNA and researchers developing new methods for the micro or non-invasive analysis of textile dyes at Nottingham Trent University and the University of Milan, who are keen to apply their developments beyond mock-up samples in laboratory conditions, optimising them for historic samples. An integral part of every stage of the research will be an ongoing comprehensive public engagement programme: from community-sourcing translators for the documents in the wallet, learning from Chinese and Indian communities in the UK about their understanding of their histories and including their knowledge of the tradition of textile making in Asia, to hands-on textile dyeing and printing workshops for families in those communities and a Maker in Residence programme.
Quantum mechanics is an "uneasy" branch of science. It is beyond our daily intuition and defies current comprehension of the physical world. But despite this, quantum mechanics has much to offer. We know that classical systems can compute, we exploit this routinely in our day-to-day life: a huge amount of information is stored and processed everyday in the classical electrical circuits of our computers, mobile phones and other devices. A similar computation can happen at the quantum level: electrons, photons, and elementary particles can store "quantum bits" of information, and when they interact those quantum bits can be processed. The exciting fact is that quantum systems can compute in an extraordinary way, much better than their classical counterpart as we are now learning. By "hacking" the computational power of the blurry quantum world, we can build quantum computers which store and process information at an unparalleled level. Problems that nowadays might overwhelm our ordinary computers for years could be solved in the blink of an eye by these extraordinary quantum machines. The impact of this "quantum information" revolution will be huge, reaching into every corner of our lives. From unconditionally secure communication to complex modelling for material and drug engineering-there is a huge number of possibilities. In order to make this a reality, it is necessary to identify, among the many quantum systems present in Nature, those that can be controlled thus providing the physical support for quantum information processing. But Nature seems jealous of her secrets -there is no definitive front-runner identified to-date. This exciting search is the main motivation of my project. An alternative approach with respect to "quantum bits" is given by so called "quantum modes". Whereas the former are quantum systems that can assume two states only (like two polarisation states of light), the latter can span over many more states (potentially infinite, similar to the infinite gradient of colours that light can assume). Historically, technological obstacles precluded control a number of quantum modes large enough to really exploit the computational power of the quantum world. However, crucial experimental breakthroughs are rapidly changing this scenario: in 2011 scientists were able to control only 10 modes at most, currently thousands be tamed! Inspired by this, the main objective of my proposal is to devise novel universal gates suited for these technologies, with the ultimate vision of unleashing the full power of quantum information. I will also assess these gates against approximation errors in realistic experimental platforms and introduce a general framework to evaluate their performances. As it is conceived, my proposal will be at the forefront of quantum information science and it will contribute to the UK and indeed worldwide effort to develop extraordinary quantum machines to deliver the next "quantum revolution".
A scientific account of consciousness is a key objective for 21st century science. A large array of consciousness-relevant empirical data has been gathered from rapidly advancing brain imaging technology, and the beginnings of theories accounting for aspects of consciousness have been formed. There is now reason to believe that we are on the verge of a major breakthrough in our understanding of what is special about the particular types of brain activity and brain tasks that are associated with consciousness. It appears that consciousness involves a precisely balanced amount of communication between the different brain regions. Too much shouting and no region can get on with processing its specifically assigned job. Too little and nothing will be tied together into a unified broadcast across the whole brain. If there is a careful balance between regional segregation and global integration of information, then the globally broadcast content will give rise to a conscious experience. This project will attempt to measure consciousness by describing this subtle property in mathematical models of brain activity. It aims to predict a person's level of consciousness by analysing brain data alone, e.g. to distinguish between whether they are fully awake, drowsy, or in deep sleep. The project will take advantage of state-of-the-art data, including `intracranial' recordings from surgically implanted electrodes that have, for medical reasons, been placed either on the brain's surface, or deep inside the brain. Analyses will be based on recordings from groups of electrodes that detect electric fields generated by the activity of large populations of neurons. Computer simulations will help identify the signatures of consciousness-related activity in the signals picked up by electrodes. A combination of new mathematical models, measures and statistical techniques will ensure that inferences about consciousness are made reliably based on properties of the data, and not from random fluctuations in activity or by inaccuracies in measurement. Consciousness science is particularly exciting because what is uncovered has profound implications for our place in nature and for our understanding of our very selves. At the practical level, having a reliable measure of conscious level would be extremely attractive in the clinic. There are scenarios in which traditional assessments of consciousness based on patient behaviour are unreliable. After a serious accident or a stroke, patients can be left in a condition in which they are completely unresponsive, yet could still be conscious and unable to communicate. This research will help inform diagnoses of patients suffering from such a disorder of consciousness, and guide ethical decisions on their treatment. This research will also find applications in psychiatry, since some mental illnesses can be considered as disorders of consciousness. Understanding the complex neural mechanisms of consciousness will open up new avenues for diagnosing mental illness and for treatment of mental suffering. This project will provide a new way of looking at `complex' systems broadly conceived as any entity that consists of many components that interact in such a way that the whole is greater than the sum of the parts. The mathematical and statistical tools developed will therefore have potential for application far beyond the study of the human brain, for example, to information technology, traffic control, climate change and finance, to name just a few domains in which complex systems arise.
Most agricultural products are derived from fruits of flowering plants, such as wheat, rice and corn. Since fruits originate from flowers, crop improvement requires a detailed understanding of flower and fruit development. Research on reference species, such as Antirrhinum or Arabidopsis, has revealed genes that control key steps in the development of flowers and fruits. These genes encode transcription factors, which regulate other genes that contain specific DNA sequences within their regulatory regions. It is believed that variation in these regulatory sequences and in their interaction with key transcription factors have played a major role in creating the changes in flower and fruit development seen during evolution and in plant domestication. We aim to understand how networks of transcription factors and their target regulatory sequences control flower and fruit development, how these networks vary between species, and explore these variations for practical use. We will focus on a key set of regulatory genes, originally identified in Arabidopsis. One of them is WUSCHEL (WUS), which controls the stem cell population that sustains development of all new plant organs. During floral organogenesis, WUS is repressed through the action of AGAMOUS (AG) and SEEDSTICK (STK). AG goes on to play a key role in specifying stamen and carpel identity, while STK guides ovule development. Under the control of AG, a further set of genes controls cell differentiation within the carpels, including the development of structures that in some species eventually allow the fruits to open and release seeds. This network includes SHATTERPROOF (SHP), FRUITFUL (FUL), JAGGED (JAG) and REPLUMLESS (RPL). We will initially use Arabidopsis to fill gaps in our knowledge of how these genes regulate each other and additional target genes during development. Each of the European partners in this project will focus on a subset of the genes mentioned above. In all cases, we will first identify the regulatory sequences that are targeted in vivo by the transcription factors encoded by these genes. We will then verify whether these target sequences are conserved across species and test their importance for the expression of the genes that contain them. We will then check whether variations in regulatory sequences can explain some of the developmental differences seen across species. In our case, we will check whether changes in the regulation of SHP, FUL, JAG and RPL are involved in the differences in fruit development between Arabidopsis and rapeseed. Based on the results, we will then perform a targeted screen for changes in regulatory sequences that may alter rapeseed fruit development for practical use, specifically, to reduce seed loss due to premature opening of the fruit.