Tuberculosis (TB) is still one of the most prevalent infectious diseases we currently face, resulting in 1.2 million deaths annually around the world. The pathogen, Mycobacterium tuberculosis (M.tb) is responsible for the onset of TB in patients by entering through the airways and activating the body's primary defence mechanisms known as the innate immune system. This involves the recruitment of many immune cells, of which include macrophages to impede the spread of the M.tb infection. Fibroblasts, a cell found in the lung also contribute to the pathogenesis of TB by secreting enzymes called matrix metalloproteinases (MMPs). MMPs are responsible for the breakdown of structural components of the lung called extracellular matrix (ECM) and in TB, there is an elevated expression of MMPs, which leads to extensive tissue remodelling and the formation of scar tissue in the lungs of patients. There is increasing evidence to suggest that immune cells such as macrophages can interact with fibroblasts to alter their function. Previous studies from my group demonstrated that M.tb infected macrophages can indirectly affect fibroblasts to enhance MMP-1 secretion, to drive the tissue destruction seen in the lungs of TB patients. One of the symptoms of TB often reported is a significant weight loss in patients, indicating that their regular metabolism is affected following M.tb infection. Furthermore, patients who are diagnosed with metabolic associated syndromes such as malnutrition or diabetes, are often linked to an increased risk of developing severe cases of TB. This highlights that M.tb heavily impacts metabolic pathways in cells during infection. Studies conducted by my group and others showed that a shift in metabolism is detected in macrophages that are infected with M.tb. However, the metabolic status of fibroblasts in TB disease or how interactions with the innate immune system regulate these underlying metabolic pathways in fibroblasts to contribute to lung tissue damage in TB is still unknown. Therefore, the main aims of my PhD project are to investigate the interface between the innate immune system and fibroblasts within the context of M.tb infection and which metabolic pathways in fibroblasts drive MMP production and hence excessive tissue remodelling seen in TB patients. To address these aims, I will use various laboratory techniques including tissue culture of human fibroblasts and immune cells such as macrophages, western blot, quantitative PCR (qPCR) and ELISA to define whether the interaction between macrophages and fibroblasts within the context of M.tb infection leads to enhanced MMP production and identify which metabolic pathway regulates these effects. This project will allow us to gain a deeper understanding about how metabolism and the innate immune system crosslink with lung cells such as fibroblasts during M.tb infection to drive lung tissue damage. As there are currently no treatments available to prevent the formation of scar tissue in the lung, this research could be used to develop novel therapeutic targets to stop excessive tissue remodelling and aid patient recovery.

Stroke is a major cause of death and disability, commonly caused by blood clots blocking large or small blood vessels of the brain. About one in five strokes are caused by disruption of blood flow in small vessels causing a lacunar stroke. This arises from diseased or hardened small blood vessels, known as small vessel disease (SVD). It can also cause widespread damage with loss of brain tissue structure, called leukoaraiosis. Lacunar stroke and leukoaraiosis is the most common cause of vascular dementia and a major cause of declining memory and thinking abilities that occurs with normal ageing. SVD is particularly common in individuals of African and African-Caribbean ancestry. It is not known why some people acquire SVD or what exactly causes it. Evidence suggests that genetic or inherited factors are important in increasing risk. However, the culprit genes have not yet been identified. New technology allows us to screen the whole of our genetic material to identify new genes causing diseases. We will examine brain scans and blood samples from stroke sufferers to try and identify genes associated with SVD in both White and Black stroke sufferers. Discovering new genes could lead to new treatments in this important disease.

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.

The impact of precarious work and labour exploitation on the health of migrant workers – the largest migrant group globally – is an extraordinarily neglected area of global research, measurement, and intervention development. Jointly, our Consortium’s work has shown migrant workers experience high rates of labour exploitation, workplace injuries, mental and physical health problems, and increasing health inequalities, yet measurement tools and interventions to protect workers remain relatively absent. Building on our systematic reviews, multi-country studies and conceptual frameworks on migrant worker health, and long-standing partnerships with stakeholders (multi-disciplinary academics from life, health, and social sciences, UN Agencies, NGOs) and, importantly, with migrant workers themselves, we will develop measurement indicators and new data-collection modules to improve evidence on migrant workers’ risk exposures and outcomes and embed them into existing global measurement surveys. We will co-develop worker-centred health intervention prototypes with migrant workers, drawing on the expertise of our transdisciplinary team (eg, health outreach models, telehealth, heat stress protocols, and health education) available open access via our global repository. We will develop and test a transdisciplinary data-to-action platform that will catalyse intervention development and coordinated action on the health burden of exploitative work.

Major progress has been made over the last two decades in reducing deaths in young children from the world's poorest countries, however death rates in newborn babies remain high. Bacterial infection is one of the commonest causes of illness and death in newborn babies across the world but is particularly problematic in low income settings. Resistance to commonly used antibiotics is increasingly seen in infections affecting young babies, and in some countries this is resulting in babies developing serious infections which cannot be treated with locally available antibiotics. Cheap, effective, readily available strategies to reduce neonatal infections are urgently required. Babies are often infected by bacteria that colonise their skin shortly after they are born. One method of reducing infection in young babies could therefore be to apply antiseptics to the birth canal of women in labour and to the skin of newborn babies to reduce the number of bacteria found on babies' skin. Finding out whether antiseptic use could reduce the number of babies developing infections will need a large, complex trial over multiple sites, but currently the best antiseptic regime to use for such a trial is not known. Our proposed study sets out to provide this information. We plan to compare two different antiseptics which are used routinely in hospitals in the care of babies and women in labour: chlorhexidine (CHG) and octenidine (OCT). We will look at how well these two antiseptics reduce the amount of bacterial present when they are applied to the birth canal of a mother and to the skin of a baby. We will also compare different frequencies of applying the antiseptics to determine which schedule works best. The study will enroll women and babies presenting to a government hospital in Malawi, one of the poorest countries in the world, and will allocate them to receive one of the antiseptic regimes. The number of bacteria present in the birth canal (women) and skin (babies) after antiseptic is applied will be tested using skin swabs. This study will carefully collect data on whether antiseptic causes skin irritation or any other problems, and will collect data from women about how acceptable it is to have antiseptic applied whilst they are in labour. The information we collect as part of this study will help decide how we design a future large study to see if antiseptics can reduce the number of serious infections occurring in young babies.