Investigate the novel therapeutic potential for treating heart failure in diabetes.

Heart failure is the most common cause of mortality in diabetes patients, but current diabetes therapies have a limited impact on the incidence of heart failure in diabetic populations. Diabetic cardiomyopathy (DCM) is a distinct myocardial disease accelerating the progression of heart failure. Diabetes stress impairs metabolic flexibility in the heart, and subsequently induces DCM, characterised by supressed fatty acid and glucose utilization, lipid accumulation, oxidative stress accompanied with profound inflammation in the heart, which eventually leads to heart failure. However, there is a dearth of effective clinical therapies for treating DCM. Thus, it is crucial to decipher the molecular pathogenesis of DCM and discover therapeutic approaches for heart failure in diabetes.

Cardiac lipid overload and inflammation have been recognized as a major pathophysiological contributor to DCM. Nevertheless, the results of some clinical trials attempting lipid-lowering and anti-inflammatory strategies in heart failure patients have not been consistent. More recently, fibroblast growth factor (FGF21) has emerged as a novel hormone regulating glucose. FGF21 analogue can lower blood glucose and has anti-inflammatory effects. FGF21 exerts its function by binding to the cell surface receptors (FGFRs) and co-receptor (Klotho) to regulate cell survival and other pivotal cellular behaviours. The pathways has showed protective roles in lowering lipids and against inflammation; however, the regulation of this pathway in cardiac lipid homeostasis and anti-inflammation is unclear.

The project is to investigate the molecular function of FGF21-FGFR1/Klotho pathway, particularly the roles in maintaining lipid metabolism and anti-inflammatory responses in the heart under diabetic condition. Given that the related treatment will be assessed on diabetic animals, this project will also provide new insights into the therapeutic implications and strategies for treating heart failure.

Training/techniques to be provided

This project will provide a comprehensive training for a PhD student in systematic and translational medicine with a wealth of animal work and molecular and cellular approaches: real-time PCR, western blot, histology, immunocytochemistry and immunofluorescence, informatics, RNA-Seq, Mass-spectrometry, ChIP assay, Luciferase assay, and sub-cloning; in vitro cell culture (primary heart cells and cell line): genetic engineering, stimulation, transfection; Animal work and assessments: genetic modified animal models, in vivo metabolic assessments (examining blood insulin, glucose and cholesterol, and measuring blood pressure), in vivo cardiac functional study (echocardiography and electrocardiography), in vivo gene therapy.

Entry requirements

Candidates are expected to hold (or be about to obtain) a minimum upper second-class honours UG degree (or equivalent) in a related subject, with or without a Master degree depending on experience. Candidates with experience in any molecular and cellular techniques or animal work or biochemistry or medicine or pharmacology with an interest in diabetes and heart diseases are encouraged to apply. 

Before you Apply

Applicants must make direct contact with preferred supervisors before applying. It is your responsibility to make arrangements to meet with potential supervisors, prior to submitting a formal online application.

How To Apply

For information on how to apply for this project, please visit the Faculty of Biology, Medicine and Health Doctoral Academy website (https://www.bmh.manchester.ac.uk/study/research/apply/). Informal enquiries may be made directly to the primary supervisor.

On the online application form select PhD Cardiovascular Sciences.

For international students, we also offer a unique 4 year PhD programme that gives you the opportunity to undertake an accredited Teaching Certificate whilst carrying out an independent research project across a range of biological, medical and health sciences. For more information please visit https://www.bmh.manchester.ac.uk/study/research/programmes/integrated-teaching/

Your application form must be accompanied by a number of supporting documents by the advertised deadlines. Without all the required documents submitted at the time of application, your application will not be processed and we cannot accept responsibility for late or missed deadlines. Incomplete applications will not be considered.

If you have any queries regarding making an application please contact our admissions team FBMH.doctoralacademy.admissions@manchester.ac.uk.

Equality, Diversity and Inclusion

Equality, diversity and inclusion is fundamental to the success of The University of Manchester, and is at the heart of all of our activities. The full Equality, diversity and inclusion statement can be found on the website https://www.bmh.manchester.ac.uk/study/research/apply/equality-diversity-inclusion/