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Novel biomarker discovery in heart failure: A metabolomics and systems biology approach


Project Description

Health failure is a highly prevalent condition, and a major cause of death and hospitalisation. Heart failure results in major healthcare costs, and much focus has been directed towards earlier diagnosis and detection, so that established treatments can be introduced.

Existing biomarkers such as the natriuretic peptides are influenced by comorbidities such as renal dysfunction, and these are more appropriate as ‘rule out’ rather than ‘rule in’ biomarkers.

Metabolomics is the study of small, organic molecules within biochemical pathways, using nuclear magnetic resonance, gas chromatography, and mass spectrometry. These have allowed for the discovery and analysis of metabolites implicated in heart failure. Metabolomics also explores links between the patient and environment interactions. Metabolomics is increasingly established as a means to develop novel biomarkers and explore new therapeutic interventions.

In a pilot study, we have identified a fingerprint of serum metabolites that characterize heart failure, and stress the potential of pseudouridine and 2-oxoglutaric acid (a-ketoglutarate in the traditional nomenclature) as novel diagnostic markers of heart failure. Importantly, there was no correlation between renal indices and metabolites and heart failure biomarkers, indicating that these were indeed biomarkers of heart failure and not renal disease per se.

The objective of the PhD studentship is to further characterise pseudouridine and 2-oxoglutaric acid as novel biomarkers in patients with heart failure, and the influence of associated comorbidities, eg. atrial fibrillation. Patients will be recruited in collaboration with hospital and community heart failure clinics run by Liverpool Heart and Chest Hospital, as well as Royal Liverpool Hospital and Aintree Hospital.

The successfully appointed student would have a background in biochemistry, systems biology or analytical science, and would have a particular interest in the analysis of ‘big data’ (for which training can be provided).

The Institute of Integrative Biology is fully committed to promoting gender equality in all activities. In recruitment we emphasize the supportive nature of the working environment and the flexible family support that the University provides. The Institute holds a silver Athena SWAN award in recognition of on-going commitment to ensuring that the Athena SWAN principles are embedded in its activities and strategic initiatives.

Funding Notes

A background in biochemistry, systems biology or analytical sciences is preferred with a particular interest in the analysis of ‘big data’ (for which training can be provided).
This would be an unfunded PhD studentship and annual £6000-12000 for research expenses may be required.

Start date would be by negotiation between the Supervisors and Student.

Informal enquiries to: Professor Douglas Kell
Professor Gregory Lip

References

Dunn WB, et al. Serum metabolomics reveals many novel metabolic markers of heart failure, including pseudouridine and 2-oxoglutarate. Metabolomics 2007; 3: 413-426

Albert CL, Tang WHW. Metabolic Biomarkers in Heart Failure. Heart Fail Clin.
2018 Jan;14(1):109-118.

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