Metabolic stress in the pathology of organ injury after cardiac surgery

The PhD student will work as part of the BHF Chair in Cardiac Surgery Research Group. This team consists of 3 laboratory scientists, 5 clinical trialists, 4 clinical academics and two administrators, and is the largest cardiac surgery research group in the UK. Our research aims to reduce deaths attributable to multiple organ failure.

Organ injury affecting the heart, lungs and kidneys occurs in more than a third of patients undergoing cardiac surgery and contributes to 41% of deaths and a 70% increase in healthcare costs. Our understanding of the underlying pathological mechanisms is poor. An established consensus developed over many years is that the inflammatory response to cardiopulmonary bypass combined with acute myocardial ischaemia reperfusion injury (IRI) results in acute metabolic stress and organ injury. However, attempts to improve patients’ outcomes by reducing inflammation or myocardial IRI have not reduced organ failure. Conversely, our recent research has demonstrated that altering a patient’s baseline metabolic state can prove effective; specifically we have shown that obese patients, and those with the metabolic syndrome, experience lower rates of organ failure.

Our ongoing programme of work, funded by the British Heart Foundation, is exploring the pathological basis of these observations. By identifying the underlying mechanisms, we believe that we may develop new therapeutic targets. We are conducting a series of randomised trials where we are altering patients’ metabolic state and assessing how this alters susceptibility to injury and the injury phenotype. The trials conducted in cardiac surgery patients will result in a biobank of samples that will include microvessels, myocardial and fat biopsies, as well as blood samples. The Ph.D. candidate will be involved in biopsies collection, dissection, and chromatin precipitation. Subsequent analysis of transcriptome, metabolome, and proteome will use next-generation sequencing and mass-spectrometry. Bioinformatical and statistical analysis of the data will identify critical pathways and molecules for further testing in vitro and biomarker discovery.

The project is an excellent opportunity for an individual interested in translational research and will provide training in necessary bench skills, proteins and nucleic acid isolation and fractionation, qRT-PCR, as well as advanced omics techniques and data analysis skills. The project will be performed in collaboration with our partners outside the UK and the applicant should be prepared to spend periods of time working in labs abroad.