University of Glasgow

My research project aims to compare Hugh MacDiarmid A Drunk Man Looks at The Thistle (1926) and Osip Mandelstam Egipetskaja Marka (The Egyptian Stamp, 1928) in order to demonstrate how Organicism strongly influenced such fragmented, universal and concrete compositions, both born under the same epistemological atmosphere, which gave shape to European Modernism. The research is believed relevant in the studies of Literary Canon since it aims to frame A Drunk Man Looks at The Thistle and Egipetskaja Marka into a broader context, align them to other European expressions of Modernism and demonstrate the unique pattern that deeply merges national literatures.

According to the WHO 235 million people suffer from asthma and 64M people have chronic obstructive pulmonary disease, leading to 3M deaths per year worldwide. The cost of treating patients with all forms of lung disease is ~ €380B p.a., leading to the loss of >50M DALYS. Generally, patients with such respiratory diseases are treated by inhalation of medicines within aerosols, where the therapy (including medicine or biologics used in gene therapy) can be targeted directly to the lung. The accepted wisdom is that such pulmonary delivery requires aerosol droplet sizes of between 1 and 5 μm. We have now shown that by using a new ultrasonic technology, we can create monodisperse aerosol droplets, which could be used for therapeutic delivery of medicines, genes and RNA to specific regions in the lungs. In one strand of the work we aim to demonstrate that this precise nebulisation technology improves the efficacy of treatment through enhanced drug uptake. In a second strand, we will demonstrate selective targeting of different tissue types in the lungs. For example, the epithelium in cystic fibrosis patients is currently extremely difficult to access leading to limitations in the amount and quality of data obtained for pre-clinical and clinical gene therapies. Similarly, targeting vascular cells is an appealing treatment for patients with pulmonary arterial hypertension, although, again, effective delivery necessitates that the therapeutic system transits defined and substantial anatomical barriers. The overall aim is to demonstrate that this new technology can define routes to new therapies, improve clinical outcomes and reduce healthcare costs. To achieve this we will develop a prototype nebuliser based upon proprietary technology and show that different medicines and gene therapies can be delivered effectively to the lungs of a model mouse. We will also start to build a commercial team and work closely with industry to deliver impact and innovation to the market.

Insecticides impregnated into bednets is the most widespread strategy to control and eliminate malaria worldwide. Insecticides work by killing mosquitoes that can transmit malaria and have been extremely successful in reducing malaria cases throughout sub-Saharan Africa. However, mosquitos are increasingly resistant to insecticides, threatening to reduce their effectiveness. Despite the gravity of this impending threat, the extent of insecticide resistance (IR) and its consequences for public health remain poorly understood. A fundamental assumption is that resistant mosquitoes are identical to susceptible ones in all aspects other than their response to insecticides. However, there are several reasons why this may not be the case. For example, malaria transmission is known to be more sensitive to variation in the long-term survival and behaviour of mosquitoes than to their overall abundance. These features, in addition to other mosquito life-history traits such as their reproductive success, may be altered in resistant mosquitoes. Together this could result in insecticide-based control methods retaining a higher than expected degree of efficacy, even in areas where IR levels are high, which would suggest the possibility of developing control methods to mitigate the consequences of resistance i.e. "resistance busting strategies". Thus understanding the ecology and behaviour of IR mosquitoes and how their life history is affected in the short and long-term by control measures is crucial for prediction of the consequences of resistance. Unfortunately, these parameters are difficult to directly measure under natural field conditions, and may be poorly reflected in laboratory bioassays. However, recent developments in ecological modelling have delivered breakthrough, but as yet rarely applied, methods for deriving such hidden (latent) information from the multiple types of data that are routinely collected in mosquito surveillance. I propose to use these new methods to investigate the population dynamics and ecology of malaria mosquitoes in an area of high IR, and to quantify the impacts of both traditional and novel control methods on mosquito life history under field operational conditions. I will focus on the Banfora district of Burkina Faso, a region of high IR, and will make use of mosquito surveillance data, including mosquito abundance, infectiousness, IR status and behaviour, being collected by my collaborators in the AvecNet programme. This data collection is part of a 2-year 90-villages large-scale intervention trial of two alternative malaria control methods for which laboratory assays predict will reduce mosquito populations through two different routes: 1) traditional bednets (LLIN) that are coated with the insecticide pyrethroid, which works by killing adult female mosquitos; and 2) new Olyset DUO nets that are coated with a pyrethroid to reduce adult mosquito survival but also with pyriproxifen, an insect juvenile hormone that affects fecundity and longevity. However, it is unclear how reliably these expected demographic impacts occur when applied within natural populations. To address these issues I will apply novel analytical tools that integrate the various types of data generated from widely-used surveillance techniques with clinical incidence data, in order to reconstruct the hidden population dynamics and life history-traits of IR mosquito vectors, and use it to 1) determine how the ecology of IR mosquitoes modulates their malaria transmission potential, 2) quantify the impacts of current and novel control methods on these mosquitoes and 3) design optimal deployment of future intervention methods in areas of high IR.

Recent developments in advanced mass spectrometry and data treatment tools have led to a boom in the efficient design of point-of-care testing (POCT). Approaches are based on novel disease biomarkers discovery with metabolomics studies and innovative sensor technologies. Breath analysis is an ideal candidate for POCT because of its non-intrusive nature; it is, however, much less developed than blood testing. Nevertheless, diseases as varied as lung and throat cancers, Parkinson's disease and pulmonary diseases have been shown to possess specific volatile biomarkers "fingerprint" which have been, to date, under-utilised. We propose therefore to move metabolomics to the headspace and study the volatilome of microbial communities to explore yet untapped opportunities for diagnostic and screening. This project entails the development of a novel pipeline for biomarker discovery in the breath volatilome (volatile metabolites), in clinically-relevant scenarios. Focusing on the oral/gut microbiome (a complex community of bacteria living at the aerobic/anaerobic interface between mucosa and oral cavity), which influences oral health (cariogenesis, periodontitis, gingivitis) and systemic and cardio-metabolic health, we propose a unique transitional approach from bench to clinical practice. During the project, analytical methods will be developed for non-targeted volatilomics using standard mixtures of representative volatile metabolites. This will include sampling, GC-MS analysis and data processing methods. Batch biofilm fermentation microcosms (in vitro) with then be ran with various treatments (such as carbon and nitrogen availability), making use of existing in vitro multi-species biofilm models established in Prof Gordon Ramage's lab. The statistical analysis tool of the pipeline will be adapted from existing tools in the Gauchotte-Lindsay group to the volatilome of these samples and biomarkers that correlate with the variations in treatment will be identified. Finally, volatilome characterisation will be carried out using the same analytical pipelines in groups of healthy human volunteers and volunteers with periodontitis and obesity-associated endotoxaemia before, during and after an intervention using dietary or pharmacological approaches to modulate the biofilm (in vivo). Here biomarkers that could eventually be employed in point-of-care sensors will be identified. Aims and objectives: This project will answer the question: Can we identify volatile biomarkers for oral health as a portal to systemic health using a novel metabolomics approach based on non-intrusive breath sampling? The aim is to produce a shortlist of chemical compounds (optimal fingerprint) that could be employed in a low-cost point-of-care sensors or lab-on-a-chip. Novelty of the research methodology: Metabolomics studies have mostly been carried out in biological samples such as blood, urine or faeces. There is growing evidence that microbial activities regulate a broad range of functions in the human body and that patients with related illness(es) present different microbiome than healthy subjects. In turns, recent research also demonstrates that the chemical composition of the headspace above a microbial community is representative of the turned-on metabolic and catabolic pathways. We propose therefore to move metabolomics to the headspace and study the volatilome of microbial communities to explore yet untapped opportunities for diagnostic and screening.

This equipment proposal is designed to enhance and maintain Glasgow and the UK's ability to stay at the forefront of the R&D of early technology critical in delivering future science goals, both for the core gravitational waves program and wider applications, at a time when the field is in a period of rapid growth. Much of the experimental work funded by our consolidated grant is in the areas of developing suspensions and in designing and measuring improved mirror coatings for the next stages of current detectors as well as for the next generation. We believe that our international competitiveness and overall impact in the field will be significantly enhanced by the purchase and development of state of the art material preparation, fabrication and diagnostic equipment to enhance our development of key technologies. Thus for our suspensions research we are requesting funding for a carbon dioxide laser, providing enhanced capabilities for the precision welding of silica and sapphire fibres to attachments bonded to the sides of test masses. This is an essential technique for the construction of mirror suspension assemblies in gravitational wave detectors, and has wider applications including the construction of components of portable atomic clocks. For our research into mirror coatings and substrates, we are requesting funding for a cryogen-free cryostat for cryogenic studies of the key properties of optical absorption and mechanical loss. Mirror coatings with low optical absorption and low mechanical loss have wider applications in the fields of quantum technology and atomic clocks. This cryostat will also enable studies of the cryogenic mechanical loss of our crystalline suspension fibres being developed for ultra-low noise performance in future gravitational wave detectors. These studies will include tests of laser-welded components fabricated with the CO2 laser requested on this grant. Finally, the cryostat will support our research into precision bonding techniques for use in the construction of the suspended mirrors used in gravitational wave detectors. To support the development and testing of new experimental systems, we request a MOKU Professional multi-instrument system. This system comprises a data logger, arbitrary and specific waveform generators, PID controller, lock-in amplifier, phase meter, spectrum analyser, digital filter algorithms and a dedicated system for laser stabilisation, all controllable through a computer interface. This will provide a highly portable system for diagnostic testing and developing experimental setups, with particular relevance for the development of our cryogenic prototype interferometer system and for the development of actuation and sensing systems for measuring the mechanical loss of mirror coatings and suspension fibres. The basic R&D in sensors for precision measurement enabled using these equipment items has wide-ranging applications in related fields including in applied optics (where our novel research on oxide bonding has enabled advances in high-power solid-state laser performance), and in coatings (where developments driven by the GW field are being adopted to created optical clocks of improved performance). We should note that none of our proposed purchases raises any issues with respect to the UKRI Framework for Responsible Innovation.