Bacterial infections have great public health and economic impact. While at present most can be treated with antibiotics, doing so requires cases of bacterial infections to be recognised early so that they can be treated with the right drugs, while ensuring that antibiotics are not given unnecessarily. With the growth in antibiotic resistance, it is becoming essential that we use these drugs appropriately. At present growth of organisms from patient samples (e.g. urine), a process which takes 18 hours or more, is usually required before specific infecting bacteria can identified. A device able to rapidly detect the presence of bacteria in such samples, and identify which species are present, without this growth step would enable doctors to make rapid and informed decisions about when antibiotic treatment is necessary and which drug should be used. Here we propose to develop and evaluate a technology for identifying bacteria in patient samples. We will combine a novel series of chemical probes (fluorescent carbon dots, FCDs) that can attach to bacteria to make them fluorescent, with an ultra-sensitive quantum photonic sensor (QPS) developed by our industrial partner, FluoretiQ Ltd., that is able to detect these fluorescent bacteria in patient samples. In order to identify individual species of bacteria we will attach specific sugars (glycans) to the surface of FCDs, exploiting the fact that different bacteria recognise particular sugar molecules as part of the process of binding to the cells of their host. We base our trials around E coli bacteria causing urinary tract infections as these are common conditions that create high workloads for NHS laboratories (our clinical partner processes up to 1000 urine samples per day) and if improperly treated can lead to severe conditions such as sepsis. We will test this methodology by assessing in the laboratory whether specific bacteria can bind to specific glycan-FCDs. A second series of laboratory experiments will then seek to replicate patient samples by suspending bacteria derived from patients, and cultured human cells, in liquid media designed to mimic the composition of human urine and testing whether glycan-FCDs bind bacteria under these conditions. Finally, with support from clinical microbiologists, we will test whether the glycan-FCD/QPS method can detect and identify bacteria in urine samples from human patients and evaluate its effectiveness compared to methods currently in use. As future users they will also help us to optimise the method and associated instrumentation to ensure that this can be used easily in the clinical laboratory, and provide guidance on how to ensure that our method can be validated against appropriate comparators and demonstrated to comply with NHS quality management systems. In parallel we will test whether glycan-FCDs can be used as the basis for new treatments for bacterial infections. We have already demonstrated that FCDs can bind to and enter bacteria; preliminary experiments show that they can also kill bacteria, in a light-dependent process. Hence we will investigate whether our modified glycan-FCDs retain the ability to kill bacteria, and whether this killing is specific to the species targeted by the particular surface sugar. We will also attach antibiotics to the surface of FCDs to test whether this represents a method to deliver drugs to specific bacteria, many of which are difficult to kill with antibiotics because the drug is unable to enter the bacterial cell. The project will establish whether glycan-FCDs can form the basis of a rapid method for detecting infecting bacteria in patient samples in the clinical microbiology laboratory, and whether these can also be used to improve the effectiveness of antibiotics against many of these organisms. In so doing we will also develop new methods for synthesising complex sugar molecules that may be applied in multiple other research areas including drug and vaccine development.

Quantum Technologies (QT) are at a pivotal moment with major global efforts underway to translate quantum information science into new products that promise disruptive impact across a wide variety of sectors from communications, imaging, sensing, metrology, simulation, to computation and security. Our world-leading Centre for Doctoral Training in Quantum Engineering will evolve to be a vital component of a thriving quantum UK ecosystem, training not just highly-skilled employees, but the CEOs and CTOs of the future QT companies that will define the field. Due to the excellence of its basic science, and through investment by the national QT programme, the UK has positioned itself at the forefront of global developments. There have been very recent major [billion-dollar] investments world-wide, notably in the US, China and Europe, both from government and leading technology companies. There has also been an explosion in the number of start-up companies in the area, both in the UK and internationally. Thus, competition in this field has increased dramatically. PhD trained experts are being recruited aggressively, by both large and small firms, signalling a rapidly growing need. The supply of globally competitive talent is perhaps the biggest challenge for the UK in maintaining its leading position in QT. The new CDT will address this challenge by providing a vital source of highly-trained scientists, engineers and innovators, thus making it possible to anchor an outstanding QT sector here, and therefore ensure that UK QT delivers long-term economic and societal benefits. Recognizing the nature of the skills need is vital: QT opportunities will be at the doctoral or postdoctoral level, largely in start-ups or small interdisciplinary teams in larger organizations. With our partners we have identified the key skills our graduates need, in addition to core technical skills: interdisciplinary teamwork, leadership in large and small groups, collaborative research, an entrepreneurial mind-set, agility of thought across diverse disciplines, and management of complex projects, including systems engineering. These factors show that a new type of graduate training is needed, far from the standard PhD model. A cohort-based approach is essential. In addition to lectures, there will be seminars, labs, research and peer-to-peer learning. There will be interdisciplinary and grand challenge team projects, co-created and co-delivered with industry partners, developing a variety of important team skills. Innovation, leadership and entrepreneurship activities will be embedded from day one. At all times, our programme will maximize the benefits of a cohort-based approach. In the past two years particularly, the QT landscape has transformed, and our proposed programme, with inputs from our partners, has been designed to reflect this. Our training and research programme has evolved and broadened from our highly successful current CDT to include the challenging interplay of noisy quantum hardware and new quantum software, applied to all three QT priorities: communications; computing & simulation; and sensing, imaging & metrology. Our programme will be founded on Bristol's outstanding activity in quantum information, computation and photonics, together with world-class expertise in science and engineering in areas surrounding this core. In addition, our programme will benefit from close links to Bristol's unique local innovation environment including the visionary Quantum Technology Enterprise Centre, a fellowship programme and Skills Hub run in partnership with Cranfield University's Bettany Centre in the School of Management, as well as internationally recognised incubators/accelerators SetSquared, EngineShed, UnitDX and the recently announced £43m Quantum Technology Innovation Centre. This will all be linked within Bristol's planned £300m Temple Quarter Enterprise Campus, placing the CDT at the centre of a thriving quantum ecosystem.