The amyloidogenic protease inhibitor Cystatin C in health and disease

Research Opportunity
PhD, Masters by Research, Honours, Master of Biomedical Science
Number of Honour Places Available
2
Department
Biochemistry and Molecular Biology
Location
Bio21 Molecular Science and Biotechnology Institute
Primary Supervisor Email Number Webpage
Prof. Jose Villadangos j.villadangos@unimelb.edu.au Personal web page
Co-supervisor Email Number Webpage
Dr. Justine Mintern jmintern@unimleb.edu.au

Project Details

Cystatin C (Cst C) is a secreted protease inhibitor. Its clinical importance as a regulator of extracellular proteolysis in the vascular system is demonstrated by the association between low serum Cst C levels and formation of atherosclerotic plaques, due in part to uncontrolled proteolytic degradation of arterial elastin. A different property of Cst C that makes this protein clinically relevant is that it can form amyloid fibrils, which are found in the cerebral vasculature of patients with neurodegenerative diseases. Such fibrils are believed to originate by a phenomenon known as “domain swapping”, whereby two Cst C monomers associate by “exchanging” subdomains to generate homodimers. These dimers can then be extended by additional rounds of domain swapping and thus form amyloid fibrils. The cells responsible for Cst C production in vascular disease are unknown. Identification of these cells, and characterisation of the mechanisms that control the synthesis and dimerisation of Cst C will lead to the development of therapeutic strategies for the treatment of diseases associated with Cst C.

Further reading: Xu et al (2014) J Biol Chem 289:9730-9740.



Faculty Research Themes

Neuroscience

School Research Themes

Cardio-Respiratory, Biomedical Neuroscience, Molecular Mechanisms of Disease



Research Opportunities

PhD, Masters by Research, Honours, 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.

Department

Biochemistry and Molecular Biology

Research Group / Unit / Centre

Villadangos laboratory: Antigen presenting cells & molecules that initiate T cell immunity against pathogens and cancer

Research Node

Bio21 Molecular Science and Biotechnology Institute

MDHS Research library
Explore by researcher, school, project or topic.