Doctoral Training Partnerships: a range of postgraduate training is funded by the Research Councils. For information on current funding routes, see the common terminology at https://www.ukri.org/apply-for-funding/how-we-fund-studentships/. Training grants may be to one organisation or to a consortia of research organisations. This portal will show the lead organisation only.

This project aims to test if the spleen is a significant source of virus and inflammatory mediators during COVID-19. The induction of a cytokine storm is the cause of pathogenic inflammation both in SARS and COVID-19. Infection of splenic CD169+ macrophages by SARS-CoV-2 has been proposed to contribute to viral spread and excessive inflammation through pro-inflammatory cell death (Park Nat Rev Immunol 2020; Feng BioRxif 2020). Our interdisciplinary team has unique expertise with splenic CD169+ macrophages as key players during systemic infection (Ercoli NatMicrobiol 2018; Chung ALTEX 2019), and with use of a human spleen ex vivo perfusion model that has been authorised for work on COVID-19 (REC 18/EM/0057). We have now confirmed that a subpopulation of human splenic CD169+ tissue macrophages express both the SARS-CoV-2 receptor ACE2 and the spike-modifying protease TMPRSS2. We now propose to exploit our whole organ ex vivo human spleen perfusion model to characterise the steps in the early phases of systemic infection. This set up allows for detailed analysis of the infectious process over time. We will test the hypothesis that these CD169+ tissue macrophages serve as a hub for systemic spread of the virus. The main outputs will be the definition of key events during tissue macrophage infection by SARS-CoV-2 in the spleen. These outputs will provide important insights into the disease process and for optimising systemic host directed treatment strategies.

Staphylococcus aureus uses host antimicrobial copper as a regulatory signal to alter gene expression to promote colonisation. The proposed project will target this response to identify new antimicrobials to treat serious S. aureus skin infection. MRSA are a cause of severe soft skin tissue infections that pose a major economic and clinical burden. The aim of this interdisciplinary project is to build on our expertise of S. aureus copper resistance, novel skin infection models and innovative imaging and mass spectrometry analysis to test our hypothesis that copper resistance plays an important role in S. aureus skin infections and identify novel antimicrobials. The objectives are to: 1. Characterise the distribution of metal and bacteria, and phagocyte responses in skin infection models. 2. Determine whether CuR alters progression to chronic infections in skin infection models. 3. Map metabolites in skin infection models to identify the metabolic status of the host and pathogen. 4. Identify novel S. aureus antimicrobials by screening the 80k compound library. The student will benefit from expertise spanning three universities: training in microbiology, highly innovative skin infection models, and imaging approaches including super resolution fluorescent and scanning electron microscopy, mass spectrometry and high throughput phenotyping to identify novel antimicrobials.

In the UK, cerebral stroke is the 3rd cause of death, the leading cause of severe adult disability in adults and costs the NHS an estimated £3 billion per year. The generation of novel and rational therapeutics is essential. Thus, every year thousands of animals are used experimentally to model stroke and investigate potential therapies. Mice are commonly used in experimental studies aimed at modelling stroke not least because they are useful for genetic manipulation studies. However, studies using experimental stroke models tend to show a large variability in the data produced. This usually results in researchers using an increased number of animals per study in order to try and detect a significant difference. We proposed that a large portion of this variability may be due to differences in the anatomy of blood vessels in the brain and an alternative approach, which we have previously developed, reduces the variability seen. Our aim here is to disseminate this refined approach within the scientific community so that other labs performing experimental stroke studies will produce data with reduced variability and therefore reduce the number of animals used in such experiments.

To analyse social data as part of developing a new generation of product that will deliver leading information and predictions to the professional investment community.