Abstracts are not currently available in GtR for all funded research. This is normally because the abstract was not required at the time of proposal submission, but may be because it included sensitive information such as personal details.

Asthma is a common lung condition with symptoms such as shortness of breath, wheeze, cough and chest tightness. Approximately 10% of individuals with asthma suffer from a severe form of the disease. They struggle to control their symptoms despite high levels of medications, resulting in lower quality of life, risk of hospitalisation and even death. New therapies are needed for this group of patients. The lungs produce the jelly-like substance mucus that acts as a gatekeeper controlling access of harmful agents (particulates, microbes, and toxins) into the body by trapping and removing them via the mucociliary escalator. However, in asthma, accumulation of mucus with abnormal properties can plug the airways worsening symptoms (known as exacerbations). The framework of mucus is provided by large molecules called mucins; in the lung there are two types of mucin (MUC5AC and MUC5B). We and others have shown that MUC5AC is increased in airway mucus in asthma. Importantly, we identified genetic changes near the genes encoding MUC5AC and MUC5B that alter the levels of these proteins and affect the risk of severe asthma. We propose a highly integrated, multidisciplinary research programme that will provide new understanding of the mechanisms that lead to the increase in mucins and how this changes the properties of the mucus in severe asthma which could lead to the development of new treatments. Main objectives: 1. Determining the genetic changes that affect MUC5AC or MUC5B expression or structure and increase risk of severe asthma. We will assess prioritised genetic changes to pinpoint which may alter the type of MUC5AC or MUC5B produced and at what level including how this is related to the risk of severe asthma. This will provide vital clues about the mechanisms involved in MUC5AC and MUC5B production. 2. Testing the effects of these genetic changes in lung cells. To understand how these genetic changes cause differences in the amount or properties of mucus proteins, we will study these genetic changes in lung cells from asthma patients. Lung epithelial cells can be grown in the laboratory to mimic the airway lining in the lung, enabling study of the different cell types present, their development and function, as well as the composition and properties of the mucins and mucus produced. We will also investigate the effects of exposing cell models to viruses known to trigger asthma exacerbations. Having identified genetic changes, we will try reversing or removing some of these changes in cell models and in human lung slices to confirm their effects on mucus production and properties. This will provide new novel targets for drug development. 3. Testing the effects of genetic changes on mucus production and composition in severe asthma patients before and during exacerbations. We will use lung biopsies and sputum samples from patients with severe asthma to identify the effects of genetic variants on the regulation and mucus composition in patients when stable or when having an exacerbation. Access to other translational studies, including intervention studies, will provide further understanding. We are bringing together international leaders in respiratory research and are employing state-of-the-art techniques spanning biology and physics to understand the mechanisms that control how mucus is regulated in our airways, how it contributes to severe asthma and how we might target it for therapeutic benefit.

We aim to develop air-stable high mobility (>0.1 cm^2/Vs) electron transporting (n-channel) organic field-effect transistors (OFETs) employing soluble fullerene derivatives. The main motivation for developing n-channel OFETs is that they enable complementary circuit design, a vital ingredient for the fabrication of the next generation large-scale, low-power, high-performance organic integrated circuits. As our material workhorse we choose the family of fullerenes due to their record-breaking electron mobility (~6 cm2/Vs). Emphasis is placed on soluble derivatives due to their processing advantage for large-area, low manufacturing cost applications. The novelty of the proposed work originates from our recent study where the first solution-processed, air-stable n-channel fullerene transistors have been demonstrated. To the best of our knowledge, this unique combination of solubility, ambient stability and electron transporting character has only been demonstrated previously in two organic molecules and can be considered as a significant breakthrough. The subject of the proposed work is very topical with huge technological importance in the area of organic electronics and it is anticipated to have significant impact both in academic research and industrial R&D worldwide.

In this project we will investigate how to make sense from sound data, focussing on how to convert these recordings into understandable and actionable information: specifically how to allow people to search, browse and interact with sounds. Increasing quantities of sound data are now being gathered in archives such as sound and audiovisual archives, through sound sensors such as city soundscape monitoring and as soundtracks on user-generated content. For example, the British Library (BL) Sound Archive has over a million discs and thousands of tapes; the BBC has some 1 million hours of digitized content; smart cities such as Santander (Spain) and Assen (Netherlands) are beginning to wire themselves up with a large number of distributed sensors; and 100 hours of video (with sound) are uploaded you YouTube every minute. However, the ability to understand and interact with all this sound data is hampered by a lack of tools allowing people to "make sense of sounds" based on the audio content. For example, in a sound map, users may be able to search for sound clips by geographical location, but not by "similar sounds". In broadcast archives, users must typically know which programme to look for, and listen through to find the section they need. Manually-entered textual metadata may allow text-based searching, but these typically only refer to the entire clip or programme, can often be ambiguous, and are hard to scale to large datasets. In addition, browsing sound data collections is a time-consuming process: without the help of e.g. key frame images available from video clips, each sound clip has to be "auditioned" (listened to) to find what is needed, and where the point of interest can be found. Radio programme producers currently have to train themselves to listen to audio clips at up to double speed to save time in the production process. Clearly better tools are needed. To do this, we will investigate and develop new signal processing methods to analyse sound and audiovisual files, new interaction methods to search and browse through sets of sound files, and new methods to explore and understand the criteria searchers use when searching, selecting and interacting with sounds. The perceptual aspect will also investigate people's emotional response to sounds and soundscapes, assisting sound designers or producers to find audio samples with the effect they want to create, and informing the development of public policy on urban soundscapes and their impact on people. There are a wide range of potential beneficiaries for the research and tools that will be produced in this project, including both professional users and the general public. Archivists who are digitizing content into sound and audiovisual archives will benefit from new ways to visualize and tag archive material. Radio or television programme makers will benefit from new ways to search through recorded programme material and databases of sound effects to reuse, and new tools to visualize and repurpose archive material once identified. Sound artists and musicians will benefit from new ways to find interesting sound objects, or collections of sounds, for them to use as part of compositions or installations. Educators will benefit from new ways to find material on particular topics (machines, wildlife) based on their sound properties rather than metadata. Urban planners and policy makers will benefit from new tools to understand the urban sound environment, and people living in those urban environments will benefit through improved city sound policies and better designed soundscapes, making the urban environment more pleasant. For the general public, many people are now building their own archives of recordings, in the form of videos with soundtracks, and may in future include photographs with associated sounds (audiophotographs). This research will help people make sense of the sounds that surround us, and the associations and memories that they bring.

Experiments using modern laser technologies and new light sources look at quantum systems undergoing dynamic change to understand molecular function and answer fundamental questions relevant to chemistry, materials and quantum technologies. Typical questions are: How can molecules be engineered for maximum efficiency during energy harvesting, UV protection or photocatalysis? What happens when strong and rapidly changing laser fields act on electrons in atoms and molecules? How fast do qubits lose information due to interactions with the environment? Will an array of interacting qubits in future quantum computers remain stable over long time-scales? Interpreting time-resolved experiments that aim to answer these questions requires Quantum Dynamics (QD) simulations, the theory of quantum motion. QD is on the cusp of being able to make quantitative predictions about large molecular systems, solving the time-dependent Schrödinger equation in a way that will help unravel the complicated signals from state-of-the-art experiments and provide mechanistic details of quantum processes. However, important methodological challenges remain, such as computational expense and accurate prediction of experimental observables, requiring a concerted team-effort. Addressing these will greatly benefit the wider experimental and computational QD communities. In this programme grant we will develop transformative new QD simulation strategies that will uniquely deliver impact and insight for real-world applications across a range of technological and biological domains. The key to our vision is the development, dissemination, and wide adaptation of powerful new universal software for QD simulations, building on our collective work on QD methods exploiting trajectory-guided basis functions. Present capability is, however, held back by the typically fragmented approach to academic software development. This lack of unification makes it difficult to use ideas from one group to improve the methods of another group, and even the simple comparison of QD simulation methods is non-trivial. Here, we will combine a wide range of existing methods into a unified code suitable for use by both computational and experimental researchers to model fundamental photo-excited molecular behaviour and interpret state-of-the-art experiments. Importantly we will develop and implement new mathematical and numerical ideas within this software suite, with the explicit objective of pushing the system-size and time-scale limits beyond what is currently accessible within "standard" QD simulations. Our unified code will lead to powerful and reliable QD methods, simultaneously enabling easy adoption by non-specialists; for the first time, scientists developing and using QD simulations will be able to access, develop and deploy a common software framework, removing many of the inter- and intra-community barriers that exist within the current niche software set-ups across the QD domain. The transformative impact of method development and code integration is powerfully illustrated by electronic structure and classical molecular dynamics packages, used routinely by thousands of researchers around the world and recognised by several Nobel Prizes in the last few decades. Our programme grant aims to deliver a similar step-change by improving accessibility for QD simulations. Success in our programme grant would be the demonstrated increase in adoption of advanced QD simulations across a broad range of end-user communities (e.g. spectroscopy, materials scientists, molecular designers). Furthermore, by supporting a large yet integrated cohort of early-career researchers, this programme grant will provide an enormous acceleration to developments in QD, positioning the UK as a global leader in this domain as we move from the era of classical computation and simulation into the quantum era of the coming decades.