Structural study of misfolding proteins
Honours projects are available in the structural characterisation of protein misfolding in amyloid diseases, such as Alzheimer’s and Parkinson’s.
A broad range of debilitating human diseases is connected with the failure of a specific protein to adopt or remain in its functional conformation and instead aggregate to insoluble deposits. These disorders - such as Alzheimer’s and Parkinson’s Diseases - impose enormous social and economic burden on society.
A major goal in attempts to understand protein misfolding diseases is to define the structures of protein species intermediate between correctly folded and aggregated, and extract a kinetic description of the aggregation process. This remains difficult, due to the inability of current approaches to analyse unstable protein complexes with structurally diverse populations. However, mass spectrometry is ideally suited to this application.
This project will use a combination of mass spectrometry based methods to probe the molecular structures and interactions along the aggregation pathway of disease related proteins, and investigate the molecular basis of inhibitors of the aggregation process, in order to identify new approaches for therapeutic intervention.
It also aims to investigate the role of different lipid environments on protein aggregation, since increasing evidence suggest lipid membranes play a critical role in protein misfolding diseases, however, the underlying molecular basis for this remains elusive.
Finally, a key challenge in protein misfolding diseases is to detect the toxic forms of protein misfolding that arise before symptoms manifest, and to specifically target these early oligomeric species in therapeutic design.
Through chemical synthesis and bioconjugation chemistry, we also aim to design novel mass spectrometry based probes for high throughput screening of protein aggregation inhibitors and enable non-invasive diagnostic strategies.
Study honours in biological chemistry
Research in the Pukala laboratories is focused on developing analytical and bioorganic chemistry approaches, primarily utilising mass spectrometry, to provide new insight into the structure, function and interactions of macromolecules important in biology.