Investigating the Dystrophin-Glycoprotein Complex to protect muscles from wasting conditions

Research Opportunity
PhD students, Honours students, Master of Biomedical Science
Number of Honour Places Available
1
Number of Master Places Available
1
Primary Supervisor Email Number Webpage
Dr Kristy Swiderski kristys@unimelb.edu.au Personal web page
Co-supervisor Email Number Webpage
Prof Gordon Lynch
A/Prof Paul Gregorevic

Summary Skeletal muscle is essential for survival. Not only is muscle the vital organ for movement but the diaphragm muscle sustains life by inflating the lungs for breathing. Skeletal muscle is also an endocrine organ that contracts and releases hormones and factors that communicate with other body tissues to sustain life.

Project Details

Skeletal muscle is essential for survival. Not only is muscle the vital organ for movement but the diaphragm muscle sustains life by inflating the lungs for breathing. Skeletal muscle is also an endocrine organ that contracts and releases hormones and factors that communicate with other body tissues to sustain life. Skeletal muscle accounts for half a person’s body mass yet we take for granted its crucial role in our health and lifestyle. Many diseases and conditions are linked with changes in muscle structure and function, including: ageing and frailty; cancer; muscle injury, sepsis and other forms of metabolic stress; nerve injury; disuse through inactivity and microgravity; burns; and different forms of muscular dystrophy. These conditions are major health problems globally and contribute to a large burden of disability and suffering. Tackling these muscle-related health conditions requires a coordinated research effort from discovery biology to understand disease mechanisms and translational approaches to take these discoveries from bench to the clinic. Researchers in the Centre for Muscle Research seek to understand the mechanisms that regulate muscle growth, wasting and metabolism, and to develop new approaches for preventing or treating muscle related conditions, utilising the latest techniques in biology and biomedicine. We also consider skeletal muscle in the context of other diseases, such as heart and cardiovascular diseases, cancer and osteoporosis. We are interested in understanding muscle development and growth, injury and repair, studying the biology and metabolism of muscle stem cells and their commitment to becoming functional muscle fibres. Our researchers design, manufacture and utilise viral vectors to alter gene expression in mouse models of disease and interrogate cellular mechanisms of muscle adaptation, techniques that provide a unique combination of speed, precision and efficacy not achieved through other approaches. The Centre for Muscle Research offers a wonderful training environment for studying muscle biology in health and disease and exceptional career-training opportunities for Honours, Masters and Ph.D. students. 

The dystrophin-glycoprotein complex (DGC) is a multi-protein structure required to maintain integrity of the muscle fibre membrane and to transmit force, by linking the actin cytoskeleton with the extracellular matrix. Importantly, we and others have shown the DGC also plays a critical role in the signalling mechanisms that maintain muscle homeostasis and membrane localisation of dystrophin is perturbed in muscles wasting as a consequence of cancer cachexia, sepsis, unloading, denervation and advanced ageing, which are all associated with low level, chronic inflammation. Identifying therapeutic approaches to restore the DGC at the muscle fibre membrane is essential for improving clinical outcomes for patients whose muscles are wasting and seemingly unresponsive to other treatments. This project will test the hypothesis that loss of DGC integrity at the fibre membrane is implicated in multiple wasting conditions and that post-translational modification modulates these DGC interactions to preserve and protect muscles in different muscle wasting states.  




Research Opportunities

PhD students, Honours students, Master of Biomedical Science
Students who are interested in joining this project will need to consider their elegibility as well as other requirements before contacting the supervisor of this research

Graduate Research application

Honours application

Key Contact

For further information about this research, please contact a supervisor.


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