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Developing novel biomarkers for diabetic heart failure


Project Description

Applications are invited for a PhD student to join the Cardiac Phenomics laboratory at the University of Melbourne. Our University is ranked 9th in the world for pre-clinical biomedical research (Times Higher Education). Successful applicants will be a part of a dynamic team with a mission to understand how the heart response to stress can be managed to minimize damage under various disease conditions. Our preclinical work, as our name suggests, looks at how the cardiac genome (genetically defined heart) is translated in different stressor situations to create the phenome (the structurally and functionally defined heart). The successful candidate will be expected to present their work at national and international conferences, and participate in collaborations with major national and international partners and local Universities/Institutes.

See our relevant publications here: https://www.ncbi.nlm.nih.gov/pubmed/?term=delbridge+lm

This project is in the field of cardiac physiology with a focus on diabetic cardiomyopathy, metabolism and failure. The early occurrence of diastolic dysfunction in otherwise ‘healthy’ asymptomatic diabetic patients has been extensively reported, and is prognostic of later occurrence of heart failure and increased mortality. Our data demonstrate that these protein modifications may contribute to impaired cardiac relaxation, indicating that small changes in protein structure can have large implications for diastolic function in diabetes. Specific characterization of these key protein modifications offers the opportunity for biomarker development for use in the early detection of subclinical diabetic cardiomyopathy and monitoring of therapies. This project will involve work with experimental models of disease and clinical biopsy samples, as part of an associated project to develop biomarkers for early detection of cardiomyopathic disease.

Specific areas of research:
- Diastolic function
- Cardiac metabolism
- Autophagy
- Cardiomyocyte mechanics and stiffness
- Proteomic alterations

If successful, you will join an active research group that utilizes state of the art techniques to discover novel therapeutic interventions. Some of these techniques include

- Cell culture and gene editing
- Crispr gene editing
- Mass spectrometry
- Working heart perfusions
- Biochemical assays
- Echocardiography
- Single cell stiffness and calcium imaging

Please see our lab website for more information about our research: https://biomedicalsciences.unimelb.edu.au/sbs-research-groups/physiology/cardiac-phenomics

Fees: If you are a new international PhD student the annual 2019 tuition fee is AUD$45,440 per annum. Fee paying positions are not available for domestic students. A Student services fee of AUD$308 per annum applied for domestic students. Scholarships to cover fees and living costs are available for competitive candidates. Please see the links in the funding section.

In brief the entry requirements to undertake a PhD at the University of Melbourne are a minimum weighted average mark (WAM) of 80% or equivalent (e.g. approx. GPA equivalent of 3.5 of a scale of 4). In addition, applicants must have completed a bachelors degree with first class honours, or a masters degree in Biomedical science, Physiology or related subject. You must have completed a substantial research project, dissertation or thesis, at university level.

Please see the following links for further information:
https://study.unimelb.edu.au/find/courses/graduate/doctor-of-philosophy-medicine-dentistry-and-health-sciences/

https://study.unimelb.edu.au/find/courses/graduate/doctor-of-philosophy-medicine-dentistry-and-health-sciences/entry-requirements/

Self funding students who have been successful in obtaining support are encouraged to apply.

For University of Melbourne, the standard scholarship application deadline for Semester 1 2020 is 31st October 2019. Late applications may be accepted for second round offers, and periodic calls for project strategic scholarship funding may also arise.

Funding Notes

A number of scholarships are available to provide support to cover fees and living costs. The scholarships are highly competitive, and you will typically need a minimum average mark (WAM) of 80% to be eligible for a University of Melbourne Graduate Research Scholarship. We highly recommend that you calculate your weighted average mark before applying. View Website

For more details on scholarships and eligibility to apply please see the links below:
Scholarships: View Website
Domestic Eligibility: View Website
International Eligibility:
View Website

References

Janssens JV, Ma B, Brimble MA, Van Eyk JE, Delbridge LMD, Mellor KM. Cardiac troponins may be irreversibly modified by glycation: novel potential mechanisms of cardiac performace modulation. Sci Rep. 2018 Oct 31;8(1):16084

Chandramouli C, Reichelt ME, Curl CL, Varma U, Bienvenu LA, Koutsifeli P, Raaijmakers AJA, De Blasio MJ, Qin CX, Jenkins AJ, Ritchie RH, Mellor KM, Delbridge LMD. Diastolic dysfunction is more apparent in STZ-induced diabetic female mice, despite less pronounced hyperglycemia. Sci Rep. 2018 Feb 5;8(1):2346

Varma U, Koutsifeli P, Benson VL, Mellor KM, Delbridge LMD. Molecular mechanisms of cardiac pathology in diabetes - Experimental insights. Biochim Biophys Acta Mol Basis Dis. 2018 May;1864(5 Pt B):1949-1959

Delbridge LMD, Mellor KM, Taylor DJ, Gottlieb RA. Myocardial stress and autophagy: mechanisms and potential therapies. Nat Rev Cardiol. 2017 Jul;14(7):412-425. doi: 10.1038/nrcardio.2017.35

Mellor KM, Varma U, Stapleton DI, Delbridge LMD. Cardiomyocyte glycophagy is regulated by insulin and exposure to high extracellular glucose. Am J Physiol Heart Circ Physiol. 2014 Apr 15;306(8):H1240-5

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