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A healthily maintained livestock is essential for the economy and prosperity of the UK. Additionally some infected livestock are the source of human diseases, particularly through foodborne infections. Historically, vaccines have been the most successful and effective intervention to reduce the burden of infectious diseases in humans. By contrast, the application of vaccines in veterinary medicine is rudimentary, mainly due to the economic necessity for reduced costs to vaccinate animals and because our knowledge of the pathogens that cause animal diseases lags behind that of human counterparts. A defining characteristic of a successful vaccine is the ability to evoke long-lasting protective immunity with minimal side effects. Many of the most successful human vaccines are glycoconjugates, a combination of a protein coupled to a glycan, which induces both a T-cell dependent and independent immune response generating a protective and lasting immunity. Examples of currently licensed human glycoconjugate vaccines include those against Haemophilus influenzae, Neisseria meningitidis and Streptococcus pneumoniae, in which glycans (lipopolysaccharides or capsular polysaccharides) are chemically coupled to immunogenic carrier proteins. However, the production of these vaccines requires multistep procedures that are often complex and expensive, and can exhibit batch-to-batch variation. We recently developed Protein Glycan Coupling Technology (PGCT) that can overcome the complex procedures required for chemically synthesising glycoconjugate vaccines by expressing the vaccine in an Escherichia coli cell in a single-step procedure. The advantages of applying PGCT to veterinary vaccines are (i) glycoconjugate vaccines can be produced at low cost, (ii) the flexibility of coupling "any glycan" with "any protein" facilitates the production of vaccine combinations providing the opportunity to evaluate a greater variety of vaccine candidates, and (iii) combination vaccines against more than one disease can be produced, further reducing cost and obviating the need to administer multiple vaccines (or antibiotics). In this study we will use PGCT to produce inexpensive triple combination poultry vaccines to reduce infection from E. coli, Salmonella, Campylobacter jejuni/coli and C. perfringens. This will not only protect poultry flocks from severe disease but would also protect the human population from the most common foodborne infections including those caused by Salmonella and Campylobacter. In addition we will construct and evaluate a dual Coxiella/C. perfringens vaccine to protect cattle, sheep and goats against severe disease. This vaccine would also prevent the spread of Q-fever to humans, which is caused by the highly infectious Coxiella burnetii pathogen. The principles developed in this proposal could subsequently be widely applied to produce inexpensive efficacious vaccines against most animal species and promise to break new ground in veterinary vaccine production.

Attention deficit hyperactivity disorder (ADHD) and autism spectrum disorders (ASD) are common childhood-onset neurodevelopmental disorders, which can co-occur. A diagnosis of ADHD and/or ASD typically gives rise to serious lifelong disabilities that cause considerable distress to individuals and their families. The transition from childhood to adulthood can be a particularly challenging time for young people with these disorders. These adults are more likely to experience a range of other behavioural and cognitive problems, yet these disorders go underdiagnosed in adults. This might reflect the presence of sub-threshold symptoms that do not meet the threshold for diagnosis but nevertheless are associated with cognitive impairment and/or mental health problems. The applicant's previous work in children who underwent comprehensive behavioural assessment has suggested that electroencephalographic (EEG) measures of executive and social function provide sensitive and objective markers that discriminate between ADHD and ASD and additionally help us understand the overlap between the disorders. However, it is currently unclear whether the cognitive impairments, symptoms of ADHD/ASD and associated emotional and adaptive functioning issues stem in part from a common cause, or rather co-occurring problems resulting from multiple causes. It is therefore of vital importance to conduct these investigations within a genetically sensitive design. To address this, we will collect data from two well-characterised twin sub-cohorts selected based on exhibiting high levels of ADHD and/or ASD symptoms in childhood. We will assess 300 twin pairs in person at ages 22-23 (200 twin pairs with at least one high-ADHD or high-ASD proband and 100 control pairs). Our proposed research has three objectives: (1) To investigate genetic and environmental origins of cognitive-neurophysiological biomarkers of ADHD and ASD and their overlap in young adulthood. Twin pairs will be assessed on executive function and social cognition tasks sensitive to ADHD and ASD symptoms. We will use innovative non-invasive mobile EEG technology to enable data collection in more familiar and natural settings, such as the home or workplace. (2) To characterise the persistence of symptoms and cognitive impairment into adulthood following a childhood diagnosis of ASD or ADHD. We will use longitudinal multivariate twin analyses to test hypotheses about development of symptoms in emerging adulthood, and further phenotypic analyses to investigate cognitive impairment even in those with sub-threshold symptoms. (3) To identify the overlap between adaptive functioning, mental health and neurophysiological function in young adults with ADHD and/or ASD. We will use the twin design to investigate the genetic and environmental origins of the overlap between symptoms, specific neurophysiological functions and mental health problems (anxiety and depression) and adaptive functioning. This will be the first study to address the aetiology of ADHD and ASD and their overlap in young adulthood using quantitative genetic and neurophysiological approaches. These data will provide information on the cognitive profiles, symptoms, mental health and adaptive functioning of people with ADHD and ASD during a critical developmental period for achieving life satisfaction and wellbeing. By using sensitive EEG measures that can be collected across abilities and environments, this project will provide the foundation for identifying objective neurobiological indices of these disorders and their outcomes in young adult life. We anticipate that this work will pave the way for identifying optimal treatment targets for these disorders and the design of more specific interventions to prevent emotional and mental health problems from developing. The innovative use of mobile EEG has the potential to transform neurophysiological research and routine clinical evaluation for psychiatric disorders.

Despite the breadth of research on climate change and the prediction of extensive population displacement, the issue of 'environmental refugee' has mostly been approached as a peripheral concern, 'a kind of aberration from the normal order of things'.

Disease of the small blood vessels within the brain (cerebral small vessel disease - or SVD) causes about a quarter of all strokes and is the main cause of vascular dementia. Its impact in causing dementia is even greater because many case of dementia particularly in the elderly are caused by a combination of stroke-like disease (primarily SVD) with diseases such as Alzheimer's. Therefore it presents a major public health problem which will only increase as the population ages. Despite its importance there are few treatments for SVD. A major problem in developing new treatments is that we don't fully understand what causes the disease and what makes it progress. Recent data has suggested two new processes may be important. One of these is leakiness of the blood brain barrier (BBB) which separates the blood vessels from the brain tissue. The second is inflammation within the brain. It is now possible to image both of these processes in patients with SVD and this is allowing us, for the first time, to determine how important these processes are in the disease. In pilot studies we have shown we can detect abnormalities in patients with SVD using these brain imaging techniques. We will now apply these techniques in more detail in this project. We will use an MRI technique in which one gives injection of a contrast agent (gadolinium) to look at leakiness of the BBB in patients with SVD. We will determine how common this leakiness is and whether patients with more leakiness have disease which progresses faster. Secondly we will use another imaging technique called positron emission tomography (PET) to image inflammation within the brain. We will determine whether BBB leakiness relates to inflammation and whether both these processes are associated with more rapid disease progression. In the final part of the project we will determine whether we can "switch off" BBB leakiness and inflammation by giving a drug called minocycline. This drug is widely used for other purposes and has been shown to switch off these both BBB leakiness and inflammation in an animal model of SVD. If we can show that these processes are important in SVD in man, and can be switched off by drugs, this will open up a completely new avenue in treatment of this important disease in man.

We are currently facing an aging population with more chronic diseases. This increases the risk of organ failure or loss as the general population live longer to face more of such health issues, hence adding further pressures of the health care system in delivering care to these affected individuals. There is increasing need for organ transplants with a growing problem of organ donor shortage. Finding other means to meet the population's growing demands is becoming ever more crucial. With advancement in technology, it is now possible for scientist to use tissue regenerative techniques to engineer new organs via the use of biological or synthetically created scaffolds to host the cells which make up the target organ. However, one of the major obstacles for growing new artificial organs is the provision of adequate blood supply to these vital cells during the period of initial implantation into the body. Lack of blood supply prevents the implanted organ from fully integrating into the body and ultimately failure of the tissue engineered structure as a whole. Hence, understanding and improving angiogenesis underpins the future success of tissue engineering of organs. The aim of this research is to increase the understanding of how we can improve the growth of blood vessels during this crucial time of integration and to be able to apply this knowledge into the development of a tissue engineered scaffold which will enable rapid growth of blood vessels to sustain its survival once implanted. In our project, we will focus on artificial windpipes as the tissue engineered scaffold model as this has been previously used in patients successfully. We have found that cells placed in a low oxygen environment will produce multiple factors which have been shown to accelerate the growth of new blood vessels. We intent to harness this unique characteristic of the cells by first implanting them into the tissue engineered windpipes scaffolds and placing them in low oxygen environments. This will trigger the release of factors which will increase the growth of new blood vessels. We will aim to see if we can demonstrate this feature when this tissue engineered construct is subsequently transplanted into living animals. It is hoped that this will show that the transplanted construct will generate and release its own factors in response to the low oxygen environment and therefore accelerate the growth of new blood vessels. The outcome from this research will help scientist gain further understanding on how to improve new blood vessel growth into tissue engineered constructs. In the long term, it may also help in the development of off-the-shelf tissue engineered products for clinical use by improving their survival in the body. It will also provide vital knowledge in achieving long-term survivorship of other artificial organs for researchers in other fields of regenerative medicine.

Quantum Simulation seeks to gain fundamental insight into the behaviour of complex microscopic systems, which underlie diverse fields ranging from materials science to chemistry and biology. New understanding can now be achieved by modelling (or simulating) this behaviour with experiments that are controllable on a microscopic, quantum-mechanical level. This provides a revolutionary approach that could solve problems that are currently intractable for even the fastest supercomputer. Ultracold atoms in optical lattices offer the unique possibility to study such behaviour of many-body quantum systems in our laboratories. In particular, a quantum gas microscope has enabled us to achieve single-site and single-atom resolved detection of fermions in an optical lattice. This exciting new tool will open the path to the study of strongly correlated fermionic quantum systems in optical lattices with unprecedented insight into their local properties, which is the core subject of the project. The following specific objectives will be addressed during the project: - Setup and characterisation of a spatial light modulator: the manipulation of atoms using laser field requires a very precise control of light potentials in both time and space. We plan to use a phase modulating spatial light modulator (SLM) to create holographic patterns at the position of the atoms. Project work comprises the setup of the SLM including all laser systems and corresponding optics in an independent setup aiming at the creation of light potentials optimised towards the desired properties, such as high contrast and spatial homogeneity. - Out-of equilibrium dynamics: A key scientific goal is to study the out-of-equilibrium dynamics of many-body fermionic quantum systems. The tailor-made light fields created by spatial light modulators will introduce local perturbations to the system, and the goal is to resolve and understand the ensuing dynamical evolution. A vast range of phenomena can be investigated, such as transport phenomena, quasiparticle propagation after quenches or spin-charge separation in a 1D system, as predicted within the theory of Luttinger liquids, which would be observable with the high resolution imaging system. - Novel techniques towards low-entropy quantum phases: Dynamically varying light potentials could also be used to implement schemes to deterministically remove high-entropy regions from the trap. In a theoretically proposed cooling scheme, it is suggested to cool fermions by separating regions of low and high-entropy in the lattice. The potential in the centre of the lattice is first lowered to a dimple to create a low-entropy (band insulator) phase. The high-entropy edges (metallic phase) are then pushed away or removed by selective addressing, thanks to the differential light shifts between the dimple and the edges. The dimple is adiabatically removed to reach a low-entropy phase with half-filling.

We propose a research platform which will explore and underpin the development of new, integrative diagnostics based on a comprehensive analysis of blood. The integration of rheological and cytometric measurements is essential to the understanding of blood as a sophisticated tissue system in which biological mechanisms, initiated and controlled by cells, interact with complex fluid dynamics. The aim is to provide an appropriate technological platform which will provide biomarkers for the detection and analysis of pathological or therapeutic modifications of blood. These research aims demand multi-disciplinary skills, significant crossover of staff between academic and clinical environments and high risk, exploratory science - all aspects appropriate to the underpinning support of a platform grant.

We seek to exploit the highly advantageous properties of III-V semiconductors to achieve agenda setting advances in the quantum science and technology of solid state materials. We work in the regime of next generation quantum effects such as superposition and entanglement, where III-V systems have many favourable attributes, including strong interaction with light, picosecond control times, and microsecond coherence times before the electron wavefunction is disturbed by the environment. We employ the principles of nano-photonic design to access new regimes of physics and potential long term applications. Many of these opportunities have only opened up in the last few years, due to conceptual and fabrication advances. The conceptual advances include the realisation that quantum emitters emit only in one direction if precisely positioned in an optical field, that wavepackets which propagate without scattering may be achieved by specific design of lattices, and that non-linearities are achievable at the level of one photon and that quantum blockade can be realised where one particle blocks the passage of a second. The time is now right to exploit these conceptual advances. We combine this with fabrication advances which allow for example reconfigurable devices to be realised, with on-chip control of electronic and photonic properties. We take advantage of the highly developed III-V fabrication technology, which underpins most present day solid-state light emitters, to achieve a variety of chip-based quantum physics and device demonstrations. Our headline goals include reconfigurable devices at the single photon level, a single photon logic gate based on the fully confined states in quantum dots positioned precisely in nano-photonic structures, and coupling of states by designed optical fields, taking advantage of the reconfigurable capability, to enhance or suppress optical processes. Quantum dots also have favourable spin (magnetic moments associated with electrons) properties. We plan to achieve spins connected together by photons in an on-chip geometry, a route towards a quantum network, and long term quantum computer applications. As well as quantum dots, III-V quantum wells interact strongly with light to form new particles termed polaritons. We propose to open the new field of topological polaritonics, where the nano-photonic design of lattices leads to states which are protected from scattering and where artificial magnetic fields are generated. This opens the way to new coupled states of matter which mimic the quantised Hall effects, but in a system with fundamentally different wavefunctions from electrons. Finally our programme also depends on excellent crystal growth. We target one of the main issues limiting long term scale up of quantum dot technologies, namely site control. We will employ two approaches, which involve a combination of patterning, cleaning and crystal growth to define precisely the quantum dot location, both based around the formation of pits to seed growth in predetermined locations. Success here will be a major step in bringing semiconductor quantum optics into line with the position enjoyed by the majority of established semiconductor technologies where scalable lithographic processes have been a defining feature of their impact.

Gene regulation is at the core of many biological processes. This project aims to examine how light signals regulate genes at the tissue level to determine whole organism responses in plants. Using the model organism Arabidopsis thaliana and specific transgenic lines developed in the Casson laboratory, this project will use next generation sequencing and bioinformatics analysis to interrogate light-dependent gene regulation at the tissue specific level. The project will examine both existing gene expression data and generate novel data sets for analysis with the aim of identifying tissue specific regulatory networks. A combination of molecular techniques including quantitative RT-PCR, reporter gene assays, Western blotting and mutant analysis will then examine the role of components of these networks in regulating light responses.

Although a growing body of research has highlighted the significance of creative labour in post-industrial societies, both as a source of economic prosperity and as a site of precarity, the transformative role played by 'disruptive' digital technologies in creative practice remains under-researched. One creative field in which digital innovations have had a particularly transformative influence is the language industry. In recent years, the labour of creative professionals such as translators, interpreters and project managers in this industry has become increasingly engaged in a complex interplay with digital technologies such as computer-assisted translation and terminology management tools, which are designed, marketed and implemented by creative professionals working at the interfaces between the language services field and the fields of computer programming and computer consultancy. Moreover, digital innovations in communication technologies and machine translation have led to the emergence of new business models based on outsourcing, crowdsourcing and automation. In response to the opportunities and risks that these developments entail, professional roles in this industry are changing and creative professionals are being encouraged to adapt to this transformational labour environment by developing new competences. This study will investigate the relationship between creative labour and digital technologies in the UK language industry to understand how digital innovations and the associated business models and imperatives for new professional roles and competences affect creative professionals' working practices in this industry. The research will be based on the analysis of interviews with creative professionals from across the UK language industry as well as the analysis of documentary sources. Drawing on Bourdieu's theory of practice and critical discourse studies, the study will develop a sociological model of current and emergent professional practice through an examination of discourses and practices within the UK language industry and at its interfaces with the creative fields of computer programming and computer consultancy. In so doing, the study aims to explain how and why language industry professionals interact with digital technologies in productive and counterproductive ways and thereby contribute to a sociologically informed understanding of the drivers of productivity in the UK language industry and wider creative economy.