Oxygen plays an important role in life on earth. The air that we breathe provides cells with the oxygen required for energy production. This need for oxygen increases for cells that rapidly multiply such as those associated with cancer; however, the supply is limited. As a tumour increases in size not all parts will be located near to vessels carrying oxygen rich blood. This results in a reduction in the oxygen levels in cells located furthest away from the blood vessel. It has been shown that these cells with low levels of oxygen (termed hypoxic) are more resistant to damage from radiation than those that are well oxygenated. This is also known to be the case for irradiation with protons. In proton therapy, a beam of protons is fired at the tumour in order to destroy the DNA in the cancerous cells, thus killing the tumour. The amount of energy and number of protons required to achieve this is determined by the tumour volume. Currently in proton therapy the tumour is irradiated such that the whole tumour volume receives the same dose (energy deposited per unit mass). If, however, parts of the irradiated tumour are more resistant to the radiation than others this technique of delivering a uniform dose across the tumour volume is not optimal. The research planned in this project aims to address this through the use of computer modelling and imaging to produce a method of increasing the dose to those low-oxygen radiation-resistant parts of the tumour whilst delivering an appropriately lower dose to the well oxygenated regions. This advancement will improve proton beam therapy and benefit any patient undergoing this form of cancer treatment. The benefits will include increased chance of survival and fewer side effects associated with the treatment

Light has been used for centuries to image the world around us, and continues to provide profound insights across physics, chemistry, biology, materials science and medicine. However, what are the limits of light as a measurement tool? For example, we can use light to image single bacteria, but can we also use light to trap a single bacterium, identify the bacterial strain and assess its susceptibility to antibiotics? How can we image over multiple length scales, from single cells to multiple cellular tissue, in order to comprehensively map all the neuronal connections in the brain? Can we use a combination of resonance with the wave nature and momentum of light to measure the forces associated with the natural and stimulated motion of a single neuronal cell, or even the extremely small forces associated with phenomena at the classical-quantum interface? This proposal aims to answer these questions by exploring new and innovative ways in which we can use light to measure the natural world. This research builds on our recent advances in photonics - the science of generating, controlling and detecting light - and in particular will exploit resonant structures and shaped light. These provide us with tools for controlling the interaction of light and matter with exquisite sensitivity and accuracy. We will run three research strands in parallel and by combining their outputs, we aim to address major Global Challenges in antimicrobial resistance, neurodegenerative disease, multimodal functional imaging and next generation force, torque and microrheology. Our work is supported by a suite of UK and International project partners (both academic and industry) who are enthused to work with us and have committed over £0.5M in kind to the programme.

In the UK one in two people are diagnosed with cancer during their lifetimes and of those who survive 41% can attribute their cure to a treatment including radiotherapy. Proton beam therapy (PBT) is a radical new type of radiotherapy, capable of delivering a targeted tumour dose with minimal damage to the surrounding healthy tissue. The NHS is investing £250m in two new "state of the art" PBT centres in London and Manchester. In addition, Oxford has attracted £110m (from HEFCE and business partners) for its new Centre for Precision Cancer Medicine, incorporating PBT. This EPSRC Network+ proposal seeks to bring the EPS community together with clinical, consumer and industrial partners and develop a national research infrastructure and roadmap in proton therapy. It capitalises on ~£300m of government investment and affords an opportunity for those not directly involved in the new proton centres to be actively involved in the national research effort in this area. This project has the backing of NCRI Clinical and Translational Radiotherapy Working Group and NHS England and will work with the national Proton Physics Research and Implementation Group of the National Physical Laboratory. It also involves industrial stakeholders, consumer groups and international partners (including PBT centres in Europe and USA and CERN). While PBT offers patients many advantages it also presents a wealth of technical challenges and opportunities where there is an unmet research and training need. This is where there the involvement of the EPS community is vital since this challenge in Healthcare Technologies requires expertise from across the EPS spectrum and maps on to themes in ICT, Digital Economy, Engineering, Mathematics, Manufacturing the Future, and the Physical Sciences and also finds synergies within quantum technologies. It directly maps onto the cross cutting capabilities identified in the Healthcare Technologies Grand Challenges. This is a highly multi-disciplinary area at the frontiers of physical intervention, which achieves high precision treatment with minimal invasiveness. This Network+ is particularly timely; it will afford the UK the opportunity to develop a world-leading research capability to inform the national agenda, capitalising on existing research excellence and the synergies that can be developed by bringing the clinical and EPS areas together. It will also collaborate with existing doctoral training provision to train the next generation of leaders where a national need has been identified. This proposed Network+ will create a national infrastructure to meet a national research and training need and will allow the UK community to work together in the multi-disciplinary field of proton research. This proposed Network+ will create a sustainable national proton beam infrastructure by drawing together sites where proton beams are already available (albeit at lower energies) and providing a route for the research community to access these facilities. As the new proton centres come on line they will add to this national resource and the centres will work together to provide a virtual national infrastructure for the UK, which by the end of the Network+ will be fully sustainable. The Network+ will also provide a route for those interested in the field but not requiring proton experiments to become involved. In addition, the Network+ will offer secondments ("Discipline Hops") into the clinical environment in both the UK and in PBT centres overseas. Working with NHS England the Network+ will develop a PBT training scheme. This will link the existing NHS provision with EPSRC Centres for Doctoral Training and allow equivalencies to be established and so provide a "fast track" to a skilled workforce and the next generation of leaders. The Network+ will also seek to engage with industry through joint research and secondments and with consumer groups, policy makers and the general public.