Dental caries is the breakdown of the hard dental tissues by the acid produced by bacteria in the mouth. It is recognised that many children and adults suffer unnecessary pain due to the destruction of the tooth and infection of the pulp (nerve). If not treated, then the tooth needs to ultimately be extracted. This non-communicable disease is entirely preventable. Eliminating the established oral biofilm that houses the bacteria that start this destructive process is however a challenge. Once bacteria break through the enamel of the tooth their passage to the pulp of the tooth is helped by the structure of dentine. This hard, dental tissue contains numerous microchannels (dentine tubules), which communicate from the external surface of the tooth to the internal pulp. The biofilm may be prevented by diet and use of fluoride toothpastes but once established is difficult to eradicate. Antibiotics are not very effective as there is no blood supply that enables them to reach the infected area and are therefore misused in the treatment of dental infections. A local treatment is proposed that allows for the rapid release of antibacterial agents at the site of infection. In this research programme we aim to rapidly tackle biofilm infections with an interdisciplinary approach based on a novel particle platform for localised drug-delivery using ultrasound as an external-physical stimulus to trigger the release of an encapsulated antibacterial agent from inside the particles. We have assembled a multidisciplinary team with expertise in chemistry, dentistry and fluid mechanics to study the ultrasound triggered activation and delivery of the silica particles in endodontic model structures, biofilms and explanted teeth. To this end we will use existing dental instruments such as ultrasonic scalers in kHz frequencies which are commonly used in dental clinics. We will employ unique flow characterisation approaches to clarify the effects of ultrasound on particle motion, directing the particles to the biofilm, and on agent release. We have chosen to work with silica particles due to their biocompatibility and the wide applicability of silica materials in dentistry. We will use particle designs to control the entrapment of the antibacterial agent which can only be released upon application of the ultrasound trigger. The particles will be developed with luminescent properties to allow optical detection of their motion in flow and to monitor the antibacterial agent release in solution. We aim to tackle problems in dental healthcare and to accelerate particle based therapies in dental practice through our impact activities. The proposed research will also provide revolutionary ways for antibiotic delivery in other areas of healthcare where localized treatment of infection is challenging (prosthetics, catheters).

Inflammatory diseases are responsible for significant death, disability and poor outcomes and are a major financial burden on the health service. Despite decades of research and billions of pounds of R&D investment, no targeted therapeutics exist that modulate neutrophils (a key cell involved in inflammation and also the major cell that surrounds lung cancers and promotes invasiveness and poor prognosis). Acute and chronic inflammatory diseases such as asthma, COPD and lung injury are common and are now increasing in incidence and severity due to the aging population. Hence, this research addresses, one of the biggest challenges facing modern drug development, the need to develop in-human assay systems that provide confidence in early trials to either continue progressing or terminating drug development programmes. A major cause for failures of drug development include the historical reliance on animal models of disease which do not accurately reflect human disease. It is essential to develop new technologies to understand and evaluate disease and drug effectiveness in vivo in situ in humans. This research proposal will develop to near-clinical readiness, novel state of the art engineering and mathematical approaches to improve the quality of the data received from a sensing system called Kronoscan which is able to image and sense in real-time at microscopic detail in new dimensions using some of the world's fastest detector technology, measuring fluorescence lifetime data of inflammatory biomarkers at video rate (>10fps). Fluorescence lifetime overcomes the significant limitations of intensity fluorescence imaging and improves quantification. In patients, we will enable this through a method called microendoscopy suited to diseases that affect the lungs and gastrointestinal tracts and other areas where we can pass small imaging fibres deep into tissue. This method will be coupled alongside chemical SmartProbes which "light" up when they interact with inflamed cells and tissues. The project will be undertaken in partnership with GlaxoSmithKline who will provide "tool" compounds in development for clinical trials. GSK already use other imaging methods such as CT Scans and PET Imaging but see this approach of adding in high resolution ultra sensitive microscopic imaging to the evaluation of drug action as a major addition to the drug development process and an essential step to improving a currently expensive and poorly productive drug development pathway. Work on the different elements needed to create this technology platform will be undertaken by investigators spanning signal processing, electrical engineering, chemistry and clinical science at the University of Edinburgh in collaboration with GSK divisions. This project will be based in the Proteus interdisciplinary "hub" to ensure rapid product development. The researchers will spend time in each others labs in Edinburgh and GSK as well as arranging an open network meeting to ensure broader engagement. The scientists (researcher co-investigators) in the proposal will benefit significantly from networking and establishing the area of next-generation in vivo pharmacology. A key ambition of the research will be to pave the way for subsequent clinical and commercial impact and as such user (clinical and regulatory) input will be paramount during the development of the technology. The team will leverage existing capability and expertise in manufacturing, regulatory and commercialisation support to expedite development. In summary, this project will generate; 1) A cutting edge point-of-care technology platform which will help drug developers, patients, doctors and health care workers throughout the world. 2) Career development of the researcher Co-Is. 3) Develop an entirely new theme with "Big Pharma". 4) A sustainable network to disseminate the technology through GSK's imaging franchise.

We will train a cohort of 65 PhD students to tackle the challenge of Data Creativity for the 21st century digital economy. In partnership with over 40 industry and academic partners, our students will establish the technologies and methods to enable producers and consumers to co-create smarter products in smarter ways and so establish trust in the use of personal data. Data is widely recognised by industry as being the 'fuel' that powers the economy. However, the highly personal nature of much data has raised concerns about privacy and ownership that threaten to undermine consumers' trust. Unlocking the economic potential of personal data while tackling societal concerns demands a new approach that balances the ability to innovate new products with building trust and ensuring compliance with a complex regulatory framework. This requires PhD students with a deep appreciation of the capabilities of emerging technology, the ability to innovate new products, but also an understanding of how this can be done in a responsible way. Our approach to this challenge is one of Data Creativity - enabling people to take control of their data and exercise greater agency by becoming creative consumers who actively co-create more trusted products. Driven by the needs of industry, public sector and third sector partners who have so far committed £1.6M of direct and £2.8M of in kind funding, we will explore multiple sectors including Fast Moving Consumer Goods and Food; Creative Industries; Health and Wellbeing; Personal Finance; and Smart Mobility and how it can unlock synergies between these. Our partners also represent interests in enabling technologies and the cross cutting concerns of privacy and security. Each student will work with industry, public, third sector or international partners to ensure that their research is grounded in real user needs, maximising its impact while also enhancing their future employability. External partners will be involved in PhD co-design, supervision, training, providing resources, hosting placements, setting industry-led challenge projects and steering. Addressing the challenges of Data Creativity demands a multi-disciplinary approach that combines expertise in technology development and human-centred methods with domain expertise across key sectors of the economy. Our students will be situated within Horizon, a leading centre for Digital Economy research and a vibrant environment that draws together a national research Hub, CDT and a network of over 100 industry, academic and international partners. We currently provide access to a network of >80 potential supervisors, ranging from leading Professors to talented early career researchers. This extends to academic partners at other Universities who will be involved in co-hosting and supervising our students, including the Centre for Computing and Social Responsibility at De Montfort University. We run an integrated four-year training programme that features: a bespoke core covering key topics in Future Products, Enabling Technologies, Innovation and Responsibility; optional advanced specialist modules; internship and international exchanges; industry-led challenge projects; training in research methods and professional skills; modules dedicated to the PhD proposal, planning and write up; and many opportunities for cross-cohort collaboration including our annual industry conference, retreat and summer schools. Our Impact Fund supports students in deepening the impact of their research. Horizon has EDI considerations embedded throughout, from consideration of equal opportunities in recruitment to ensuring that we deliver an inclusive environment which supports diversity of needs and backgrounds in the student experience.

Doctoral Training Partnerships: a range of postgraduate training is funded by the Research Councils. For information on current funding routes, see the common terminology at https://www.ukri.org/apply-for-funding/how-we-fund-studentships/. Training grants may be to one organisation or to a consortia of research organisations. This portal will show the lead organisation only.

Doctoral Training Partnerships: a range of postgraduate training is funded by the Research Councils. For information on current funding routes, see the common terminology at https://www.ukri.org/apply-for-funding/how-we-fund-studentships/. Training grants may be to one organisation or to a consortia of research organisations. This portal will show the lead organisation only.