In the UK, one in two people will be diagnosed with cancer during their lifetime and of those who survive, 41% can attribute their cure to a treatment including radiotherapy. Radiotherapy is very cost effective, accounting for only 6% of the total cost of cancer care in the UK. In radiotherapy the way the radiation dose is delivered and conformed to the tumour uses a treatment plan, which is based around a CT scan of the patient and their tumour. The treatment plan uses beams of radiation at different angles, to maximise the dose (and damage) to the tumour and to minimise the damage to the surrounding healthy tissue. Constraints are also applied for "organs at risk" which are often more sensitive to radiation and so require the dose to be as low as possible. Radiotherapy is normally delivered in fractions, with a fraction being typically 1-2 Gy. A course of radiotherapy is typically 1 fraction every week-day over a period of 4-6 weeks. Radiotherapy seeks to maximise the damage to the tumour (to sterilise it) while minimising the damage to the surrounding healthy tissue (to reduce side effects). In recent years radiotherapy has developed rapidly with the development of new machines and methodologies. These in turn, have resulted in better imaging, treatment planning and dosimetry, which enable the dose to be more accurately delivered and conformed to the tumour. This has resulted in better cancer survival and reduced side effects for patients. However, to maintain this rate of advancement and deliver even better treatments for patients we require innovation and solutions to the challenges, which still confront advanced RT. This is exactly where the STFC community can make an enormous impact, working in partnership with the clinical community, as they together they have exactly the skill set which is needed to effectively tackle these new challenges as they arise. In addition, the latest developments in radiotherapy - such as MR-linacs and proton therapy - evidence the need for the STFC community to work in partnership with the clinical community and commercial partners. If the UK is to remain competitive and deliver even better treatments for patients, and produce income and impact for the UK economy, it can no longer rely on serendipitous partnerships. This is what this Advanced Radiotherapy Network + (ARN+) seeks to address. Working actively with the clinical community through the National Cancer Research Institute (NCRI) Clinical and Translational working group on Radiotherapy (CTRad) it has been able to establish a new community drawn from across STFC with clinicians and clinical scientists from the NHS. This application is an extension of an existing successful ARN + and is aimed at both consolidating the success of the ARN+ and taking it one step further by developing a global dimension for its activities by working with the IAEA. It also seeks to showcase its activities to industry and develop a pipeline of innovation to the clinic. Finally it looks to work with STFC within the framework of UK Research and Innovation to build a national consensus, research roadmap and funding strategy in the field of Advanced Radiotherapy.

The terahertz (THz) frequency region within the electromagnetic spectrum, covers a frequency range of about one hundred times that currently occupied by all radio, television, cellular radio, Wi-Fi, radar and other users and has proven and potential applications ranging from molecular spectroscopy through to communications, high resolution imaging (e.g. in the medical and pharmaceutical sectors) and security screening. Yet, the underpinning technology for the generation and detection of radiation in this spectral range remains severely limited, being based principally on Ti:sapphire (femtosecond) pulsed laser and photoconductive detector technology, the THz equivalent of the spark transmitter and coherer receiver for radio signals. The THz frequency range therefore does not benefit from the coherent techniques routinely used at microwave/optical frequencies. Our programme grant will address this. We have recently demonstrated optical communications technology-based techniques for the generation of high spectral purity continuous wave THz signals at UCL, together with state-of-the-art THz quantum cascade laser (QCL) technology at Cambridge/Leeds. We will bring together these internationally-leading researchers to create coherent systems across the entire THz spectrum. These will be exploited both for fundamental science (e.g. the study of nanostructured and mesoscopic electron systems) and for applications including short-range high-data-rate wireless communications, information processing, materials detection and high resolution imaging in three dimensions.

Quantum technologies promise a transformation of measurement, communication and computation by using ideas originating from quantum physics. The UK was the birthplace of many of the seminal ideas and techniques; the technologies are now ready to translate from the laboratory into industrial applications. Since international companies are already moving in this area, there is a critical need across the UK for highly-skilled researchers who will be the future leaders in quantum technology. Our proposal is driven by the need to train this new generation of leaders. They will need to be equipped to function in a complex research and engineering landscape where quantum physics meets cryptography, complexity and information theory, devices, materials, software and hardware engineering. We propose to train a cohort of leaders to meet these challenges within the highly interdisciplinary research environment provided by UCL, its commercial and governmental laboratory partners. In their first year the students will obtain a background in devices, information and computational sciences through three concentrated modules organized around current research issues. They will complete a team project and a longer individual research project, preparing them for their choice of main research doctoral topic at the end of the year. Cross-cohort training in communication skills, technology transfer, enterprise, teamwork and career planning will continue throughout the four years. Peer to peer learning will be continually facilitated not only by organized cross-cohort activities, but also by the day to day social interaction among the members of the cohort thanks to their co-location at UCL.

This proposal requests funding to purchase a sample probe and superconducting magnet to be used for a magnetic resonance spectrometry at the University of Birmingham for scientific research by a broad range of users from across the United Kingdom. This probe and magnet will be used to characterize the structures and interactions of animal, plant and microbial proteins and metabolites. This information will be used to understand the functions of these molecules in solutions similar to those in the interior of a living organism or cell. In order to obtain such information, very weak electromagnetic signals originating from the hydrogen, nitrogen and carbon atoms of the protein must be detected. The requested probe offers the highest possible level of sensitivity for these experiments, allowing researchers to observe molecules that are rare, difficult or expensive to produce, or insufficiently soluble or stable at the high concentrations required for NMR analysis. The cryogenic probe allows one to either lower the concentration of the sample or reduce the time required to obtain NMR spectra of proteins. New experiments that are otherwise precluded by sensitivity requirements can be used, allowing larger proteins and rare small molecules to be detected and data to be collected more quickly. The requested magnet offers the latest in superconducting technology at a magnetic field strength of 14 Tesla. This magnet offers excellent separation of the hydrogen, nitrogen and carbon signals, and represents the state-of-the-art standard for metabolomics and ligand discovery research. In addition this magnet is actively cooled and actively shielded, meaning that it recycles helium and does not require weekly maintenance, thus reducing manpower costs in an environmentally friendly manner. The research that would be enabled by this probe focuses on proteins and biochemical systems which are involved in regulation of cell growth, and the control of the metabolic and signalling pathways within several organisms. The organisms to be studied include food-borne pathogenic bacteria, models for genomics such as Dictyostelium, aphids and the Arabidopsis plant, zebrafish, and mammalian tissues including the human brain. The availability of this probe and magnet would be a major draw for new users, allowing more experiments to be performed, better quality data to be collected, and new projects initiated and supported within a new national facility used for internationally competitive research in the post-genomic sciences.

Miniaturisation of electronic devices has been matched in recent years by a drive to create miniature Lab-on-Chip systems that can handle and analyse chemical and biological materials in tiny volumes. Ultrasonic standing-wave fields are a promising technology that can potentially achieve many of the functions required for Lab-on-Chip systems, including: pumping, mixing, cell lysis, cell sorting, and sonoporation (opening pores in cell walls to allow drugs or genetic material to enter). Most importantly, by establishing and shaping the acoustic field bacteria and other biological cells can be manipulated and levitated within fluidic devices. In contrast to other technologies, it is possible to manipulate thousands of cells at once without harming them. However, controlling these various functions and preventing interactions in the confines of a microfluidic system is challenging and prevents wider uptake of these technologies. Research is required to better understand how secondary effects interfere with the primary functions. One example is the disruption of manipulation by acoustic streaming (a movement of the fluid itself induced by the ultrasound). Using novel techniques such as surface structuring I will enable the streaming flows to be controlled, and put to practical use (e.g. to enhance diffusion for cell perfusion, and analyte diffusion in sensor systems). Initial modelling suggests that this approach could enhance streaming by a factor of 10, leading to applications in other domains such as micro-cooling systems. I will be researching several other key areas: The mechanical stimulation of cells with acoustic forces to direct the development of mechanically responsive cells such as stem cells; the integration of ultrasonic arrays into microfluidic devices for enhanced flexibility of manipulation; and ways to integrate multiple acoustic functions within a single disposable device. The fundamental research will both enable and be driven by the second focus of the fellowship, applications. Two applications that each have the potential to transform existing technologies will be developed: 1) Bacterial detection in drinking water: My team has recently proven that bacteria (who typically experience forces 1000x smaller than human cells) can be successfully concentrated in flow-through ultrasonic devices. As part of a European project we have used this to concentrate the bacteria in samples of water to enhance the detection efficiency. However, I believe that we could deliver around a 100-fold increase in sensitivity by using the ultrasound to drive bacteria directly towards an antibody coated sensor surface where they will be captured and optically detected. Deploying such devices widely would be very beneficial for detecting contamination of drinking waters, rivers, and industrial waste streams. 2) Drug screening system: I will create a system that forms arrays of tiny clusters of human cells. Cells cultured in this 3D environment behave more naturally than those grown on a petri dish. The cells will be held in place by acoustic forces, both levitated away from contaminating surfaces, and also held against a steady flow of nutrients over a period of several days. Drugs will be introduced into the flow, and an integrated laser based detection system will monitor the resulting metabolites produced by the cells. The advantage of this is that large numbers of drugs can be tested in parallel, identifying those that could be further developed. A strong motivation for this application is that by providing a representative model of human tissues it could reduce the number of animal experiments required for drug testing. Given the huge potential impacts of these and other related systems I will work closely with industrial companies that have experience of creating detection and analytical systems to bring our technologies into widespread use.