Degree Name

Doctor of Philosophy


School of Chemistry and Molecular Bioscience


The maintenance of cellular protein homeostasis, or proteostasis, is dependent upon a complex network of molecular chaperones, degradation machinery and other regulatory factors, which together act to keep the proteome soluble and functional. Disturbances to proteostasis can lead to protein aggregation and inclusion formation, processes associated with a variety of neurodegenerative disorders. The heat shock proteins (Hsps) are a superfamily of molecular chaperones that are dramatically upregulated in response to cellular stress. The Hsps can bind aggregation-prone proteins and either refold or traffic them for degradation. One class of Hsps, the DNAJBs, act as co-factors of the Hsp70 machine and have been previously identified as potent suppressors of disease-related protein aggregation. This has raised the potential of targeting DNAJB chaperone action in the context of protein aggregation associated with disease.

In the work described in this thesis, a destabilised isoform of the protein firefly luciferase (R188Q/R261Q Fluc; FlucDM) was overexpressed in cells to assess how components of the proteostasis machinery engage with aggregation-prone proteins to prevent them from forming intracellular inclusions.

FoR codes (2008)

0601 BIOCHEMISTRY AND CELL BIOLOGY, 060106 Cellular Interactions (incl. Adhesion, Matrix, Cell Wall), 060108 Protein Trafficking, 060109 Proteomics and Intermolecular Interactions (excl. Medical Proteomics)



Unless otherwise indicated, the views expressed in this thesis are those of the author and do not necessarily represent the views of the University of Wollongong.