Sialic acids as biomarkers for cardiovascular disease

Cardiovascular disease (CVD) is a major cause of morbidity and mortality, particularly in the West. Therefore there is a continued need for the identification of risk factors and disease markers, in order to allow early intervention, and better clinical outcomes, as well as develop methods for primary prevention. In some cases, the incidence of CVD in patients varies in a way that cannot be explained using recognized risk factors and markers, again highlighting the need for the identification of new biomarkers. Many large biomolecules in the body contain a particular carbohydrate called sialic acid (SA). This can exist in different forms. Previous studies have shown that SA levels are high in patients at risk of CVD. However, studies have not analytically detailed the different forms of SA in such patients in any depth. Increasing our understanding of the different SAs in blood and saliva samples from healthy subjects, as well as those at risk of CVD, and correlating those analytical observations with CVD risk and diet, is the main aim of this three year project.
During this industrial CASE award, different derivatives of SAs will be prepared at the University of Reading, using innovative chemical and enzymatic methods. The derivatives will then be included within well developed analytical protocols at the laboratories of Ludger Ltd that include chromatography and mass spectrometry. Patient focused studies will be undertaken at the University of Reading to obtain saliva and blood samples from both healthy volunteers and those who are at risk of CVD. The samples will be analysed at the laboratories of Ludger Ltd to determine biomarker features of the different forms of SA that are present. These levels will be compared with other CVD risk factors and the volunteer's diet, to see whether there are any correlations, using statistical methods.
Training will be provided throughout the programme in synthetic and analytical chemistry, and in carbohydrate profiling, within a Medicinal Chemistry context. As part of the programme the student will undertake placements at the laboratories of Ludger Ltd, at the Culham Science Centre in Abingdon. In addition to enhancing the progress of your PhD programme, the placements will also be used to show you how to undertake your work to a level that is recognised as good practice by the Federal Drug Administration (FDA) and the European Medicines Agency (EMA).