Palmitoylation and the regulation of the “funny” current HCN4 channel

Applications are invited for a PhD studentship in the laboratories of Dr Will Fuller (Division of Molecular & Clinical Medicine, University of Dundee) and Professor Jules Hancox (School of Physiology and Pharmacology and Neuroscience, University of Bristol). The project will characterise a novel regulatory mechanism of the ion channel ‘HCN4’, which controls the rate of the heart’s intrinsic pacemaker. The project will therefore provide new insights into a hitherto overlooked mechanism by which cardiac pacemaker activity could be modulated.

The Role of Inflammation in Predisposition to Cardiovascular Disease Risk in South Asians: A Comparison of Populations in Scotland and Singapore

It is now well established that atherosclerosis is an inflammatory disease with a broad array of inflammatory cells and pathways implicated at every stage of the disease [1]. Acute and chronic inflammation are key factors in the development of endothelial damage [2,3]. As endothelial dysfunction is a validated biomarker for future cardiovascular events, closer study of the role of inflammation in early-stage endothelial dysfunction should be undertaken, particularly in high risk populations.

Chronic Heart failure [CHF] and the study of pharmacogenomics: Towards customized medicine in CHF therapy

There is increasing evidence that genetic variability can play an important role in inter individual response to medication. Variants of genes have been reported to modulate the response to drugs that are used in heart failure such as beta-blockers and diuretics. However their impact on outcome is yet to be established and it is likely that many other as yet undiscovered variants are likely to also have a significant impact.

The genomics of cardiovascular disease and drug response in type 2 diabetes

The field of personalised medicine is being transformed by the use of whole genome technology.  We are currently studying a population of 9000 individuals with type 2 diabetes to determine the genetic factors in determining their response to a wide range of commonly used drugs such as the statin family of cholesterol lowering drugs and anti-clotting agents such as aspirin.  The use of these drugs may be limited by side effects such as muscle pain, in the case of statins, and stomach bleeding in the case of aspirin.   We have performed a whole genome scan in 8000 individuals with type 2 diab

Linking Genomics to Imaging data: Elucidation of the mechanisms of novel genes that predispose to heart disease

Genome wide studies have provided great insight into the truly polygenic nature of cardiovascular disease, with current meta-analysis being performed in populations of ~200,000 study individuals.  This has characterised around 60 loci involved in susceptibility to CAD.  This analysis combines a wide range of cardiovascular phenotypes including angina, IMT, atheroplasty and MI. So the role of these genes in individual components of cardiovascular disease such as atherosclerosis, vessel damage, heart muscle physiology etc. has not yet been elucidated.

Hypoglycaemia in the post-infarct period induces cellular oxidative stress

Elevated glucose at presentation with an acute coronary syndrome is associated with a poor outcome. However, clinical intervention trials have shown that normalization of glucose in the post-infarct period does not improve outcomes and may actually increase cardiovascular mortality particularly when associated with hypoglycaemia.. This studentship examines the hypothesis that hypoglycaemia in the post-infarct period induces cellular oxidative stress, and in vulnerable ischaemic tissue exacerbates myocardial damage.

Regulation of the Sodium Pump By Palmitoylation of its Accessory Subunits

The plasmalemmal sodium pump is the principal consumer of ATP in the body. In cardiac muscle, the pump is essential for normal cardiac function. In skeletal muscle, the sodium pump controls extracellular potassium concentration and therefore membrane potential and muscle fatigue. In the kidney, the ion gradients established by the pump are critical for reabsorption of water and solutes throughout the nephron, and therefore in the control of blood volume, blood pressure and cardiac load.

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