Mapping ceramides in atherosclerotic plaques to understand the role of lipids in cardiovascular disease

About the project

About the Project This studentship aims to uncover the mechanistic basis of why fats, and in particular a subset of fats called ceramides, are independent risk factors for cardiovascular disease (CVD) by studying the lipid composition of atherosclerotic plaques - the deposits of fat, cholesterol and dead cells that accumulate in arteries and lead to CVD and heart attacks. In international studies using mass spectrometry to study the fat content of blood, certain ceramides (referred to as long-chain ceramides) have been used to refine risk models of primary and secondary CVD events, with these lipids being used within clinical CVD tests in the USA and Finland to identify those who will benefit from more aggressive treatments. Such biomarkers could revolutionise how we target treatments to vulnerable patients. However, we do not understand the mechanistic basis of why these lipids are associated with CVD – and without this understanding, these lipids cannot be used for diagnosing human disease with high confidence. One theory as to why certain ceramides are associated with CVD is that these ceramides are responsible for unstable regions in plaques that lead to cardiovascular events (heart attacks and strokes). Using state-of-the-art mass spectrometry imaging (MSI) we will study ceramide deposition in plaques extracted from patients with CVD. Conventional microscopy will be performed alongside, staining for different regions of the plaque, allowing us to cross-correlate metabolic changes with features in the plaque at the cellular level. In this manner, the student will directly test whether ceramides accumulate in unstable plaques, validating treatments that target ceramide production for CVD and other chronic disorders. Essential background of student Suitable candidates will have completed an undergraduate degree or equivalent in either chemistry, biochemistry, biological sciences, medical sciences or medicine. We do not expect candidates to have experience of all the techniques proposed for the studentship, but some prior experience of analytical chemistry, cell culture, molecular biology, or metabolism would be desirable. Experience of R or python would be a real asset. Where will I study? This studentship will be based in the Rowett Institute and the Institute of Medical Sciences, both within the School of Medicine. Medical Sciences and Nutrition at the University of Aberdeen. In addition, the student will make use of the NHS Grampian Biorepository at Aberdeen Royal Infirmary. Training: Project specific training for this studentship will be provided by members of the Griffin group, which includes five (4.5 FTE) post-doctoral researchers and fellows and 2 (1.6 FTE) technical assistants, particularly in mass spectrometry, imaging and multivariate statistics. Where required further training courses have been accessed either through the manufacturer of the instrument (including in person training on the instrument) and international societies such as the Metabolomics Society. The student will undertake generic skills training organised by the School of Medicine, Medical Sciences and Nutrition. An important part of a student’s training is taking part in scientific meetings/conferences and presenting their data either as talks or as posters. The student will be encouraged to participate in local and national meetings of learned societies and other professional networks, where appropriate and guided by the supervisor. Of relevance to this studentship is the annual Scottish Metabolomics Network meeting, as well as the biannual Metabomeeting and focused meetings on mass spectrometry imaging (e.g. by the British Mass Spectrometry Society). Aberdeen and Aberdeenshire: Scotland’s third largest city, Aberdeen sits on the coast between the mountains of Aberdeenshire and the stunning North Sea coastline. Renowned as a Global Energy Hub, Aberdeen is a vibrant, entrepreneurial region, home to a unique mix of business opportunities and specialist skills across various sectors including energy, technology, life sciences and food & drink. More than 20% of Scotland’s top businesses are located in this region which is taking great strides to ensure that it continues to compete on a world stage. Investments of more than £10 billion of public and private infrastructure is due to be delivered before 2030, marking an exciting time to be part of a genuine world-class location. Built from sparkling local granite Aberdeen has earned the name of the Silver City. As the energy capital of Europe, Aberdeen nevertheless retains its old-fashioned charm and character making it an attractive place in which to live, work and study. Due to its global business and international energy industry credentials, Aberdeen is well served by local and national transport infrastructure with excellent rail networks that run both North and South of Scotland and the rest of the UK. It also acts as an international travel hub. Flying time to London is just over one hour with regular daily flights and serves international travel to European centres such as Amsterdam (Schiphol) and Paris (Charles de-Gaulle) as well as flights to other European destinations. The City and the surrounding countryside provide a variety of urban, seaside and country attractions. Aberdeen has first-class amenities including His Majesty’s Theatre , Music Hall , Art Gallery , the P&J Arena , Museums , and Beach Leisure Centre . The City is framed by its accessible beachfront, which is within a short walk of the city centre, and there are an array of activities available across the region such as hill walking; mountaineering; sailing; surfing; salmon, trout and sea fishing; golf; sailing; surfing and windsurfing. The surrounding countryside, known as Aberdeenshire, is also one of Scotland’s most appealing regions. Royal Deeside and the Cairngorms National Park are within easy access of the city, and there are a variety of towns and villages scattered along the coastline. The city and the surrounding area have ranked consistently highly in nationally recognised quality of life surveys, coming out top 10 as one of the best places to live in Scotland in 2020 in the annual Bank of Scotland survey. To find out more, visit www.visitabdn.com

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