The Univeristy of Melbourne The Royal Melbourne Hopspital

A joint venture between The University of Melbourne and The Royal Melbourne Hospital

EDUCATION

Research Projects

Project: The amyloidogenic protease inhibitor Cystatin C in health and disease

Villadangos Group

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

Contact project supervisor for further
information and application enquiries

Project Supervisor

Professor Jose Villadangos

Project availability
PhD/MPhil
Master of Biomedical Science
Honours

Villadangos Group

[email protected]

3 vacancies

Themes
Immunology
Host Pathogens Interactions
Cross Cutting Disciplines
Discovery Research
Translational and Clinical Research

The Villadangos group studies the first event that triggers adaptive immune responses: the presentation of pathogen or tumour antigens to T cells by dendritic cells, B cells and macrophages. We are characterising the development, regulation and impairment of antigen presenting cells by pathogens, inflammatory mediators and tumours. We are also dissecting the biochemical machinery involved in antigen capture, processing and presentation. We use this knowledge to understand how T cell-dependent immunity is initiated and maintained, and apply it to design better vaccines and immunotherapies against infectious agents and cancer.


Villadangos Group Current Projects