Molecular sciences, such as chemistry, biophysics, molecular biology and protein science, are vital to innovations in medicine and the discovery of new medicines and diagnostics. As well as making a crucial contribution to health and society, industries in this field provide an essential component to the economy and contribute hugely to employment figures, currently generating nearly 500,000 jobs nationally. To enable and facilitate future economic growth in this area, the CDT will provide a cohort of researchers who have training in both aspects of this interface who will be equipped to become the future innovators and leaders in their field. All projects will be based in both molecular and medical sciences and will focus on unmet medical needs, such as understanding of disease biology, identification of new therapeutic targets, and new approaches to discovery and development of novel therapies. Specific problems will be identified by researchers within the CDT, industrial partners, stakeholders and the CDT students. The research will be structured around three theme areas: Biology of Disease, Molecule and Assay Design and Structural Biology and Computation. The CDT brings together leading researchers with a proven track record across these areas and who have pioneered recent advances in the field, such as multiple approved cancer treatments. Their combined expertise will provide supervision and mentorship to the student cohort who will work on projects that span these research themes and bring their contributions to bear on the medical problems in question. The student cohort approach will allow teams of researchers to work together on joint projects with common goals. Projects will be proposed between academics, industrial partners and students with priority given to those with industrial relevance. The programme of research and training across the disciplines will equip graduates of the CDT with an unprecedented background of knowledge and skills across the disciplines. The programme of research and training across the disciplines will be supplemented by training and hands-on experiences of entrepreneurship, responsible innovation and project management. Taken together this will make graduates of the CDT highly desirable to employers, equip them with the skills they need to envisage and implement future innovations in the area and allow them to become the leaders of tomorrow. A structured and highly experienced management group, consisting of a director, co-directors, theme leads and training coordinators will oversee the execution of the CDT with the full involvement of industry partners and students. This will ensure delivery of the cohort training programme and joint events as well as being accountable for the process of selection of projects and student recruitment. The management team has an established track record of delivery of research and training in the field across industry and academia as well as scientific leadership and network training coordination. The CDT will be delivered as a single, fully integrated programme between Newcastle and Durham Universities, bringing together highly complementary skills and backgrounds from the two institutions. The seamless delivery of the programme across the two institutions is enabled by their unique connectivity with efficient transport links and established regional networks. The concept and structure of the CDT has been developed in conjunction with the industrial partners across the pharmaceutical, biotech and contract research industries, who have given vital steer on the desirability and training need for a CDT in this area as well as to the nature of the theme areas and focus of research. EPSRC funding for the CDT will be supplemented by substantial contributions from both Universities with resources and studentship funding and from industry partners who will provide training, in kind contribution and placements as well as additional studentships.

LightOx, an SME based in Newcastle upon Tyne, are developing LXD191, a novel light-activated therapy targeted as a preventative treatment to eliminate early-stage/precancerous lesions that arise in the mouth before they can develop into challenging cancerous tumours. LXD191 is a molecule that, when activated by light from an LED device, elicits the generation of radical oxygen species (ROS) that are highly toxic towards precancerous cells and tissues. This kind of behaviour is common in molecules known as photosensitisers, typically utilised for a type of light-activated treatment known as photodynamic therapy (PDT). However, LightOx believe LXD191 operates through a novel mechanism that is distinct from common photosensitisers and has not been reported in the literature before. Learning more about the unique activity of LXD191 will help LightOx progress this new molecule into clinical trials and to develop innovative light-activated products for other challenging diseases. To help them understand this fascinating new drug molecule, LightOx have formed an exciting partnership with leaders in spectroscopy and photochemistry at University College London (UCL) and the Science and Technology Facilities Council's Central Laser Facility (CLF) to develop a project that aims to fully understand the unique behaviour of LXD191, and to help LightOx bring this innovative therapy to clinical utility. The project team, comprising Dr. David Chisholm of LightOx, Prof. Helen Fielding of UCL, and Dr. Igor Sazanovich, Dr. Partha Malakar and Dr. Sneha Banerjee of the CLF are aiming to utilise the world-leading facilities at UCL and the CLF to investigate LXD191 using two cutting-edge techniques: time-resolved infrared spectroscopy (TRIR) and transient absorption spectroscopy (TA). Both techniques examine the changes that occur to LXD191 at the precise moment it is activated by light and how the molecule utilises energy from the light. TRIR measures changes in precise vibrations that occur within the bonds of LXD191's chemical structure, while TA measures the energy that this structure absorbs. These data can help build a computational model to describe how LXD191 interacts with light that the team can use to understand how this molecule destroys precancerous and cancerous cells. There are around ~8800 cases of oral cancer diagnosed in the UK each year, with most presenting at an advanced stage with poor prognosis. The incidence has been increasing for decades, particularly in those over the age of 50, and mortality rates are not improving. Around 50% of patients die within 5-years of diagnosis, whilst a reliance on invasive surgery (used in 95% of cases) means that survivors are left with severe life-long impacts affecting swallowing, eating and speech. Prevention strategies are urgently needed to address this increasing burden of disease. LXD191 promises to be the first preventative treatment for early-stage/precancerous lesions that progress to oral cancer and this project is aimed at characterising the novel activity of LXD191 to help accelerate its development towards clinical trials, and advance the understanding of light-activated chemical processes.