Lifestyle behaviours, such as whether we smoke and drink alcohol, how much we eat, and the amount of exercise we take, have a major impact on our health and mental health. This programme will focus on improving our understanding of why people engage in unhealthy behaviours, what the consequences of these behaviours are for our health and mental health, and what we can do to encourage people to live healthier lifestyles. It will draw on a wide range of different techniques, including epidemiology, genetics, epigenetics, laboratory studies and clinical trials. Lifestyle behaviours represent the primary modifiable causes of illness and premature death in developed countries such as the United Kingdom, and anything which improves our understanding of these behaviours has the potential to dramatically improve public health.

By harnessing the unique properties of quantum mechanics (superposition and entanglement) to encode, transmit and process information, quantum information science offers significant opportunities to revolutionise information and communication technologies. The far-reaching goal of this project is to build quantum technology demonstrators that can outperform conventional technologies in communications and computation. For quantum information technologies (QITs) to have as big an impact on society as anticipated, a practical and scalable approach is needed. One promising approach to QITs is the photonics implementation, where single particles of light (photons) are used to encode, transmit and process quantum information – in the form of photonic quantum-bits (qubits). Currently, state-of-the-art experiments are limited to the “few-photon” regime, occupying many metres of space on an optical table, constructed from bulk optical elements, with no routes to scalability and far from outperforming conventional technologies. Integrated quantum photonics has recently emerged as a new approach to address these challenges. This research programme will take an engineering approach to QITs and draw upon rapidly growing field of silicon photonics. We will develop a silicon-based quantum technology platform where single-photon sources, circuits and detectors will be integrated into miniature microchip circuits containing thousands of discrete components, enabling breakthroughs in quantum communications and computation, and developing a scalable approach to quantum technologies. There are no new physics breakthroughs required to achieve the goals of this project, however, there are hard engineering challenges that need to be addressed.

Cell surface carbohydrates play key roles in cell recognition mechanisms. O-glycosylation is a ubiquitous post-translational modification that is highly dynamic and responsive to cellular stimuli through the action of cycling enzymes. Expression of specific O-glycans is linked to changes in gene expression in, for example, inflammatory bowel disease, cystic fibrosis and several types of cancer. Protein-carbohydrate interactions typically exhibit high specificity and weak affinities toward their carbohydrate ligand. This low affinity is compensated in nature by the architecture of the protein, the host presenting the carbohydrate ligands in a multivalent manner or as clusters on the cell or mucosal surface. This effect is known as the multivalency or “cluster–glycoside effect” and has been well documented for lectin–carbohydrate interactions as increasing ligand affinity and selectivity. The fundamental understanding of these glycosylation patterns at molecular and functional levels will allow mechanisms associated with bacterial-host interactions, bowel disease and several cancers to be defined, which will facilitate the identification of effective treatments and diagnostics for these conditions in due course. This is a multidisciplinary project involving synthetic organic and inorganic chemistry, enzymology and glycobiology. The proposal centres on the development of expedient synthetic and chemo-enzymatic methodologies for the preparation of novel multivalent O-glycan probes that will be used in the screening of O-glycosylation-linked interactions in health and in disease. These studies will help us understand the parameters controlling the combinatorial diversity of O-glycans and the implications of such diversity on receptor binding and subsequent intracellular signalling, which in turn will lead us to the development of new glycan-based diagnostic tools and therapeutics.

Gene therapy is one of the most innovative and fastest growing fields in the pharmaceutical industry. The first approved gene therapy utilized a recombinant AAV vector (rAAV), and dozens of additional rAAVs for gene therapy are presently in clinical trials. rAAV gene therapy drugs have been priced in the region of € 500’000 and above, which is partially a result of them being manufactured by highly complex processes combining multiple components, requiring 5-7 separate GMP production runs. We intend to introduce the first scalable, single-virus rAAV production platform to resolve this bottleneck. The resulting significant reduction of manufacturing complexity will both lower the price of future rAAV gene therapies, and also deliver additional, currently unaddressed or unaffordable rAAV treatments for genetic diseases into the clinic by providing scientists operating at the laboratory R&D stage with more user friendly and productive tools. The proposed project also develops for PoC purposes an rAAV gene therapy candidate to treat the devastating childhood congenital disease known as steroid resistant nephrotic syndrome SRNS.