Global warming caused by greenhouse gases like CO2 is a major global concern. Understanding the complex natural cycling of greenhouse gases is crucial to address the urgent climate crisis. The cycling of key greenhouse gases, like CO2, involves microorganisms that fix CO2 and release methane. Some microorganisms also utilise intermediates like carbon monoxide (CO) and dihydrogen (H2) in their metabolism. The metabolic pathways of these microorganisms involve specialised gas-processing enzymes, which are key to understand how greenhouse gases can be fixed from the atmosphere, and directly related to biogeochemical cycles, global warming, and climate change. This project aims to develop new biohybrid catalysts by utilising biological scaffolds to host or bind synthetic catalysts. Biohybrid catalysts hold a lot of potential to fix greenhouse gases from the atmosphere and for carbon capture and storage (CCS). They are sustainable, as they are biodegradable and produced from naturally abundant materials. Biohybrid catalysts combine the advantages of synthetic chemistry with the benefits of natural enzymes (specificity/selectivity). However, biohybrid catalysts based on protein scaffolds from 'regular' organisms are generally restricted to ambient conditions, limiting their scope for application in biotechnology. Extremophiles are organisms that live under extreme environments, such as under high pressures and extremes of temperature and pH. Evolution of organisms under extreme conditions has optimised their enzymes for exquisite performance under harsh conditions. This project aims to make use of the unique properties of extremophiles by mining their genomes in search of ideal scaffolds for synthetic catalysts to build biohybrid catalysts that can work under non-ambient conditions. This project will encompass three main stages. Stage 1 will focus on searching for (i) small metalloproteins from extremophiles including enzymes active for CO2 reduction and/or H2 conversion and (ii) small proteins like ferredoxins and cytochromes. In Stage 2, the identified enzymes/proteins will be produced and characterised to test their stability under extreme conditions. In Stage 3, the produced enzymes will be tested as candidates for binding synthetic catalysts. Overall, this project will develop new approaches for environmental biotechnology to fix greenhouse gases from the atmosphere and for CCS by building biohybrid catalysts using biological scaffolds from extremophiles. Methodology: The research plan breaks down as follows: 1) Analysis of databases (e.g. metagenomic databases) will be done to identify homologues of well-known hydrogenases (enzyme that catalyse H2 conversion in nature), CO dehydrogenases (enzyme that catalyse the CO2/CO interconversion in nature), as well as ferredoxins and cytochromes that are present in extremophiles. 2) The organisms of interests will be obtained and cultured in the lab to purify the enzymes. 3) In parallel with the step 2, the enzymes will be produced heterologously (e.g. inside E. coli or other hosts). 4) The structure/function of the enzymes will be studied via an integrated approach combining electrochemical, spectroscopic, structural and computational methods. 5) The produced enzymes will be tested as candidates for binding/hosting synthetic catalysts and the reactivity of the biohybrid catalysts will be explored.

An exciting aspect of Nanotechnology is its multidisciplinarity that crosses barriers between physics, chemistry and biology. Recently it has been explored for new cancer therapies, which conventionally use toxic drugs resulting in a balancing act between harming the patient and treating the cancer. A nanotechnology-based approach is to use magnetic nanoparticles less than 10 nanometres across (5,000 times smaller than the width of a human hair) attached to ‘targeting molecules’ that locate and attach only to cancer cells. Once in place an oscillating external magnetic field heats the particles and their attached cells, thereby killing them, without harming healthy tissue. This gentle treatment is the so-called ‘magic bullet’ approach and has been shown to work in principle in early clinical trials but is hindered by the available nanoparticles not producing enough heat. In a recent breakthrough at Leicester, the Condensed Matter Physics group in Physics and Astronomy developed a new method of producing suspensions of highly magnetic bio-compatible nanoparticles that will generate 5-10 times as much heat per particle as existing fluids. The grant will support a collaboration between Physics, Chemistry and the Leicester General Hospital to develop the technology, conjugate the nanoparticles with targeting molecules and test the new suspensions for their tumour-killing performance in vitro.

It is very difficult to find out whether potential risk factors for disease, such as alcohol consumption or aspects of people s diet, really have causal effects on diseases such as heart disease and cancer. Rapid developments in genetics mean that we now know about genetic variants that influence these factors. This can happen either because your genes influence the amount of a substance such as vitamin D that circulates in the blood, or because your genes influence your behaviour, such as the amount of alcohol you consume. Because your genes are a random sample of your parents genes ( Mendelian randomization ), it is possible to use genetic variants associated with modifiable risk factors of interest to study whether these risk factors really have causal effects on diseases. The statistical methods used to analyse these studies are called instrumental variables methods. These methods require development in order to make them useful in Mendelian randomization studies, including finding ways to check the assumptions made in these studies. This project aims to develop instrumental variables methods, and to apply them in particular examples of importance in medical research.

ARM Parallel Debugging and Profiling Application: This is an application that supports the debugging, profiling and optimisation of codes that use distributed resources, such as a cluster. It is both CPU and GPU enabled. This package will also enable jobs to be analysed in terms of code efficiency. Reports generated using ARM Forge are being used to improve system design, architecture performance and application performance. The licence will be purchased on behalf of the ExCALIBUR H&ES programme for use at all ExCALIBUR sites. The cost is for one year (April 2023 to March 2024). This request was approved by the ExCALIBUR H&ES programme, to be funded at 100%.

Project Highlights: Develop new understanding of anthropogenic emissions from point sources Generate evidence for joined up climate and air quality policy Drive the development of the next generation of satellite remote sensing techniques Overview (including 1 high quality image or figure): As we move toward stricter air quality guidelines and more ambitious climate targets, it is imperative that we understand emissions from key point and small area sources such as power stations, mines, landfills, and other industrial facilities, in order to best target our efforts. We additionally need to monitor changes over time to evaluate the effectiveness of reduction measures. To do this on a global scale we must utilise current and future satellite technologies and high-resolution atmospheric models. This project will utilise current satellite data and the cutting-edge model WRF-Chem to understand greenhouse gas and air pollutant emissions from important point sources including power stations, mines, and landfills. Evaluation of performance of satellite data will be conducted, and evidence for policy pathways explored. Data from Sentinel 5P TROPOMI will be used in the first instance, with a focus on nitrogen dioxide and methane emission quantification. This will be coupled with the WRF-Chem model. Requirements for future data streams will be defined, with a view to satisfying the needs of policy decisionmakers of the future. A key element of this PhD will be understanding how environmental data products and analysis can be generated to best meet the needs of policy stakeholders. The supervisory team have strong links with local, national and international policy stakeholders in both air pollution and greenhouse gas contexts. In addition to providing evidence for policy, this PhD will also develop advice on what future satellite observations are needed, and feed into building the case for future missions for air quality and greenhouse gas remote sensing, to ensure that future generations have a high quality long term record of point source emissions as policies and technologies evolve. Methodology: Data from Sentinel 5P TROPOMI will be used in the first instance, with a focus on nitrogen dioxide and methane emission quantification from important point sources. This will be coupled with the WRF-Chem model. You will first apply existing methodologies to quantifying emissions of these two gases, and relate those to other emissions. You will then build upon these methods to develop new techniques and expand to additional atmospheric species. Following this, you will generate a novel point source emissions catalogue for greenhouse gas and air pollutant emissions, compare these to bottom-up estimates calculated for the facilities, and put this information into a format actionable by policy stakeholders and site operators. You will then utilise these data to conduct joined up analysis for targeted emission reduction measures in the context of joined up air quality and climate change policy development.