The green macroalgae, or seaweeds, are one of the most common sights on beaches and shorelines around the UK, providing food and shelter for many marine animals. The most familiar of these green seaweeds are the Ulva species; the 'sea lettuces'. These are particularly important because they act as a link between the land and the seas; increased nutrient run-off from agricultural fertilisers, or from urban sewage treatment plants, can lead to higher nutrient levels in the rivers and seas that border farmlands and cities. These enriched waters, which can also occur naturally through the spring upwelling of nutrient-rich deeper sea waters, can, in turn, see extraordinarily rapid growth of the seaweeds that live in them; the so-called 'green tides' that can choke coastal waters worldwide and which are responsible for threatening the Olympic sailing regatta at Qingdao in 2008, covering beaches along the south coast of the UK in 2010, and fouling the Breton coast annually. We still know very little, however, about these astonishingly important organisms. The proposed research aims to provide the first genome sequence of one of these green seaweeds, Ulva compressa, giving us a first look at their genomic architecture and at the genes which allow them to grow so dramatically. The UK has a strong tradition of green seaweed research, and this proposal would add to that tradition by providing a framework on which to hang 'Next Generation' genomic experiments that look at the ecology and biology of marine seaweeds.

The Twilight Zone spans from 100m to 1000m depth in the ocean. It is a region where very little light penetrates and where little is known about the processes that take place within it. Each year, nearly as much plant material is produced by microscopic plankton in the surface ocean as by all the land's forests and plains. Although created in the sunlit top 100m, this organic material eventually sinks, potentially taking a huge amount of carbon with it deep into the ocean interior where it could be trapped, away from the atmosphere, for up to hundreds of years. All but a few percent of this material is converted back into carbon dioxide within the Twilight Zone. To understand the role that marine life plays in regulating carbon dioxide in the atmosphere it is thus crucial to understand what controls this enormous recycling activity in the Twilight Zone. The UK is world-leading in this area, recently providing the first "budget" for how the Twilight Zone processes carbon. UK projects currently extend from the North Atlantic to the Southern Ocean and represent an investment of over £9M. Simultaneously there are similar current projects in the US and Spain totalling £19M, with major projects being developed in France and Germany. A new US project alone has received £26M from the Audacious Project (previously TED) fund to explore the Twilight Zone. Although each project tackles different aspects of the functioning of the Twilight Zone, by bringing them together a much more profound analysis is possible than by one alone. Working together there is a once-in-a-generation opportunity to revolutionise how we understand the functioning of the Twilight Zone. Therefore BIARRITZ will seek to create something even greater than the sum of these already significant parts by using two linked approaches. It will provide fora for the projects to meet, to share data, best practice and novel approaches, to pool data from the huge span of environments they encompass and to initiate collaborations to address gaps identified by this interaction. It will also lead by example, to stimulate the necessary four types of collaboration, by initiating four small scale collaborations representing something old, something new, something borrowed and something out-of-the-blue. These seedcorn collaborations will have the primary purpose of providing incentive to the BIARRITZ community to develop a larger network of collaborations, but they will also significantly enhance the scientific insights from an ongoing research programme: - 'Something old' is to reinforce existing collaborations. In BIARRITZ we re-establish a collaboration with a French expert in measuring how much carbon enters the top of the Twilight Zone. - 'Something new' is to build new collaborations. In BIARRITZ we begin a collaboration with an American world-leading expert on dissolved organic carbon, to quantify the importance of this little studied pathway into the interior. - 'Something borrowed' is to bring in new skills and equipment. In BIARRITZ we will be trained by a French researcher whose equipment allows us to quantify the 'dragon kings' of the ocean, the large particles that may dominate the downward rain of material deep in the ocean. - 'Something out-of-the-blue' is to provide opportunities for young scientists outside the established projects. In BIARRITZ we will provide a young US researcher with his first opportunity to deploy a new high-tech approach to measuring organic carbon in the open ocean. These small scale collaborations will exploit the NERC CUSTARD project which, as part of the Role of the Southern Ocean in the Earth System programme (RoSES), is investigating how marine life, in the remote part of the S. Ocean southeast of the Tierra del Fuego, influences the global carbon budget. This both provides BIARRITZ with a unique platform for these collaborations and in turn significantly enhances the understanding that will be gained from CUSTARD and RoSES.

The last 20 years have witnessed a remarkable growth in the field of THz frequency science and engineering, which has matured into a vibrant international research area. The modern THz field arguably began with the development of a pulsed (single-cycle) THz emitter - the semiconductor photoconductive switch - and the subsequent development of THz time-domain spectroscopy (TDS). Since then, considerable success has been achieved in the further development of this and other THz sources, including the uni-travelling carrier (UTC) photodiode and the quantum cascade laser (QCL). However, notwithstanding this, it is only the THz-TDS technology that has been developed sufficiently for commercialization as a complete system, leaving other THz devices, components and techniques still restricted to the academic laboratory. This is unfortunate, since despite the success of THz-TDS, the technique has a number of shortcomings including its high fs-laser dominated cost, low power, and limited frequency and spatial resolution, which could be addressed by QCL and UTC technologies if they were to be engineered into appropriate instruments. In fact, a cursory comparison with the neighbouring microwave and optical regions of the spectrum reveals that THz frequency science and technology is still in its infancy, and not just in the context of commercial uptake. For example, the THz region significantly lags in the availability of precision spectroscopy instrumentation required to address sharp spectral features inherent to gases, for example, in atmospheric analysis, or in materials with long excited state lifetimes. THz technology also significantly lags in the fields of non-linear spectroscopy and coherent control, where powerful and controlled pulses of electromagnetic radiation interact with matter and manipulate its properties. In the optical and microwave regions, fascinating phenomena including electron-spin resonance and nuclear magnetic resonance were major breakthroughs, revealing a wealth of new science and engineering applications. These techniques, now standard across many disciplines, support much contemporary research and technology activity. A further example of how THz technology compares unfavourably with other spectral ranges is in the context of THz microscopy and analysis below the diffraction limit, which intrinsically restricts such measurements to ensemble sampling of physical properties averaged over the size, structure, orientation and density of, for example, nanoparticles, nanocrystals or nanodomains. Although near-field imaging approaches have been adapted from the visible/infrared regions enabling THz measurements on the micro/nano-scale, no THz instrument currently provides the required spatial resolution and sensitivity, nor can address the enormous range of length-scales (spanning five orders of magnitude from electron confinement lengths (<10 nm) to the THz wavelength (~300 um)), nor can operate at cryogenic temperatures. In fact, on this point, the THz field is deficient even in the provision of basic technologies such as waveguides and coupling optics required to deliver THz signals with low loss into cryostats or industrial apparatus. In this programme we will create the first comprehensive instrumentation for precise THz frequency spectroscopy, microscopy, and coherent control. This will be based upon our unique and proprietary capabilities to generate, and manipulate photonically, THz signals of unprecedentedly narrow (Hz) linewidth and with sub-wavelength spatial resolution. The instrumentation will then be exploited to create new challenge-led applications in non-destructive testing and spectroscopic analysis for electronics and atmospheric sensing, inter alia, as well as discovery-led opportunities within physics, quantum technologies, materials science, atmospheric chemistry and astronomy.

Computational biomedicine offers many avenues for taking full advantage of emerging exascale computing resources and, as such, will provide a wealth of benefits as a use-case within the wider ExCALIBUR initiative. These benefits will be realised not just via the medical problems we elucidate but also through the technical developments we implement to enhance the underlying algorithmic performance and workflows supporting their deployment. Without the technical capacity to effectively utilise resources at such unprecedented scale - either in large monolithic simulations spread over the equivalent of many hundreds of thousands of cores, in coupled code settings, or being launched as massive sets of tasks to enhance drug discovery or probe a human population - the advances in hardware performance and scale cannot be fully capitalised on. Our project will seek to identify solutions to these challenges and communicate them throughout the ExCALIBUR community, bringing the field of computational biomedicine and its community of practitioners to join those disciplines that make regular use of high-performance computing and are also seeking to reach the exascale. In this project, we will be deploying applications in three key areas of computational biomedicine: molecular medicine, vascular modelling and cardiac simulation. This scope and diversity of our use cases mean that we shall appeal strongly to the biomedical community at large. We shall demonstrate how to develop and deploy applications on emerging exascale machines to achieve increasingly high-fidelity descriptions of the human body in health and disease. In the field of molecular modelling, we shall develop and deploy complex workflows built from a combination of machine learning and physics-based methods to accelerate the preclinical drug discovery pipeline and for personalised drug treatment. These methods will enable us to develop highly selective small molecule therapeutics for cell surface receptors that mediate key physiological responses. Our vascular studies will utilise a combination of 1D, 3D models and machine learning to examine blood flow through complex, personalised arterial and venous structures. We will seek to utilise these in the identification of risk factors in clinical applications such as aneurysm rupture and for the management of ischaemic stroke. Within the cardiac simulation domain, a new GPU accelerated code will be utilised to perform multiscale cardiac electrophysiology simulations. By running large populations based on large clinical datasets such as UK Biobank, we can identify individual at elevated risk of various forms of heart disease. Coupling heart models to simulations of vascular blood flow will allow us to assess how problems which arise in one part of the body (such as the heart) can cause pathologies on remote regions. This exchange of knowledge will form a key component of CompBioMedX. Through this focussed effort, we will engage with the broader ExCALIBUR initiative to ensure that we take advantage of the efforts already underway within the community and in return reciprocate through the advances made with our use case. Many biomedical experts remain unfamiliar with high-performance computing and need to be better informed of its advantages and capabilities. We shall engage pro-actively with medical students early in their career to illustrate the benefits of using modelling and supercomputers and encourage them to exploit them in their own medical research. We shall engage in a similar manner with undergraduate biosciences students to establish a culture and practice of using computational methods to inform the experimental work underpinning the basic science that is the first step in the translational pathway from bench to bedside.

Multiferroics and magnetoelectrics are materials that develop a ferroelectric polarization in a magnetic state, either spontaneously or in a magnetic field. Because they can in principle convert electric into magnetic signals, it has been proposed that they could be used as key components in a new generation of information storage and processing devices, alternative and better than the familiar magnetic (e.g., hard disks) and ferroelectric (e.g., smart-card chips) storage media. A true renaissance in the field was triggered by the discovery of a new class of multiferroics, in which magnetism and ferroelectricity are tightly coupled. However, after almost a decade of research, no material has yet emerged as a viable candidate for applications, since the observed effects are weak and generally restricted to low temperatures. Here, we propose to explore at the fundamental level a number of novel concepts, which depart in a radical way from the thoroughly-explored `cycloidal magnetism' paradigm. In particular, we will attempt to unlock the potential of the strongest of the mageto-electric interactions, the so-called `exchange striction' effect. In contrast to the weaker effects mostly considered so far, obtaining electrical polarisation from exchange striction requires an exquisite control of the crystal symmetry and of the magnetic interactions at the atomic level. We propose to employ an innovative research methodology, which combines conventional measurements of electrical and magnetic properties, `imaging' of the spins and electric dipoles at different length-scales, from atomic to macroscopic, and state-of-the-art ab-initio theoretical calculations of the static and dynamic properties of these systems, both at low temperatures and at room temperature. The breakthrough we seek is a new microscopic "working principle" that can be deployed to perfect practical multiferroics and magnetoelectrics materials. Our new approach, which strongly emphasizes the interface between theory and experiments, will also pave the way for similar studies on related classes of materials, with applications in information storage, energy conversion and storage and many others.