Current Projects
Project 1: Engineering of hydrophobins
(in collaboration with A/Prof Margie Sunde and A/Prof Suchowerska)
Hydrophobins are fungal proteins that spontaneously self-assemble at hydrophobic:hydrophillic interfaces to form robust and amphipathic coatings
In nature, hydrophobin coatings provide protection and water proofing of fungal structures e.g. spores, as well as mediate interactions with hosts during fungal infections
Advantages of hydrophobins in biotech applications include: spontaneous self-assembly, robust coating, structure tolerant to mutations including additional of functional groups, biocompatibility and non-immunogenicity
We have shown that hydrophobins can be modified to have reactive groups at specific positions that enable biotech applications
Can we expand the functionality of hydrophobin coatings through “smart” protein engineering?
Together with researchers at the Chris O’brien Lifehouse, we are currently engineering hydrophobins that can promote the adhesion and growth of osteoblasts in PEEK bone implants.
We are currently looking for an Honours or internship or PhD student interested in biotechnology/engineering to carry on the baton from Erica.
NMR structure of the hydrophobin EAS in ribbon and surface showing distinct hydrophobic (grey) and hydrophilic faces (red and blue).
Hydrophobins can spontaneously coat a number of substrates and modify their properties, including dispersing nanodiamonds in water as shown on the left panel. The right panel shows naked nanodiamonds aggregating in water.
Hydrophobin coating changes the properties of a surface as indicated by the different shapes of water droplets on Teflon.
Project 2: Developing specific inhibitors that target periodontal diseases
(in collaboration with Dr Jinlong Gao)
Docking studies showing how haem and a prototype “Trojan” inhibitor bind to HusA
Porphyromonas gingivalis is a “keystone” pathogen in chronic periodontitis which affects a quarter of the world’s population
Symptoms include inflammation and bleeding which eventually lead to destruction of tooth and supporting structures
Haem uptake system protein A (HusA) is a haem-binding protein that is necessary for P. gingivalis to grow under iron-restricted conditions, e.g. in plaques
We have determined the structure of HusA and performed docking studies with haem and analogues. This has allowed us to design and test the idea of “Trojan horse” inhibitors. We are working on improving the specificity and potency of the lead compounds.
Scope for a new PhD project involving NMR structure determination and binding studies
Project 3: Investigating cellular signaling in novel cancer therapies
(in collaboration with A/Prof Suchowerska and Prof McKenzie)
When cancer cells are exposed to ionising radiation, they experience a number of physical and biochemical changes
Certain irradiation schemes/spatial patterns are more effective at killing cancer cells (e.g. non-small cell lung cancer cells) at the same dose
Can this be due to certain irradiation patterns resulting in signals being passed from “targeted" cells to neighbouring "bystander "cells?
We track these signals using metabolomics
This project combines analytical techniques, data science, biostatistics and biochemistry
Schematic of cell culture after an irradiation pattern that leads to some cells being irradiated (“targeted”, red) amongst non-irradiated neighbours (“bystanders”, grey).
http://www.mylifehouse.org.au/departments/radiation-oncology/
Project 4: Developing new antibiotics by targeting specific molecular interactions in bacteria
(in collaboration with Dr Sandro Ataide)
Antibiotic resistance is an increasing problem globally and may bring about the end of modern medicine as we know it
Predictions suggest the number of death from drug-resistant infections will surpass those from cancer by 2050
New antibiotics are urgently required but their discovery has slowed dramatically in the last two decades
Our solution involves developing a new class of broad spectrum antiobiotics by targeting a never exploited interaction between bacterial Signal Recognition Particle (SRP) and its Receptor (SR)
We have identified a number of small molecule fragments and analogues which can target SR and some of which have antibacterial properties
This project has recently been selected to join the SPARK Translational Program!
We are currently seeking a highly motivated undergraduate TSP/DSP/Honours student with a strong interest in translational research to join our project.
E. coli SR binding to SRP-RNA
We have been using the Fragment-based drug design approach to find inhibitors of bacterial SR
Faoro et al PLoS One, 2018
E. coli SRP:SR structure solved using X-ray crystallography