• Australian Research Council Large Equipment and Infrastructure Fund Grants
• West Australian Future Health Research and Innovation Fund
• Australian Research Council Discovery Project Grant

Collaborators

• Assoc. Prof Keith Stubbs, Chemistry, UWA;
• Prof Charlene Kahler, Microbiology, UWA
• Assoc. Prof Matthew Piggott, Chemistry, UWA
• Dr. Willem Lesterhuis, Biomedical Sciences, UWA
• Dr. Flora Meilleur, Oak Ridge National Laboratory, USA
• Dr. Mitali Sarkar-Tyson, Biomedical Sciences, UWA
• Dr. Yit Heng Chooi, Biochemistry and Molecular Biology, UWA
• Dr. Monika Murcha, Biochemistry and Molecular Biology, UWA

CHEM1002 - Chemistry: Structure and Reactivity

BIOC1001 - Introductory Cellular Biochemistry

BIOC2002 - Biochemical Regulation of Cell Function

BIOC3001 - Molecular Biology

BIOC3002 - Structural and Functional Biochemistry (Unit Co-ordinator)

MSCI4006 - Advanced Techniques in Molecular Sciences

BIOC4002 - Fundamentals of Biochemistry and Molecular Biology

Prof Vrielink uses protein crystallography and Electron Microscopy to study the 3D structures of macromolecules. In particular, she is interested in studying enzymes involved in redox catalysis, bacterial membrane biosynthsis and bacterial pathogenesis as well as proteins involved in the gene transription and multienzyme proteins involved in substrate channeling. Understanding the structures of these macromolecules provides important insight into their molecular and biological functions. A number of projects are listed below:

• In collaboration with Prof Charlene Kahler (Microbiology and Immunology), Assoc. Prof Keith Stubbs (Chemistry) and Prof Martin Scanlon (Monash University) Prof Vrielink is working in the area of endotoxin biosynthesis in Neisseria meningitidis and Neisseria gonorrhoeae the causative agents of meningitis and gonorrhea. Endotoxin molecules on these bacteria are decorated with multiple phosphoethanolamine (PEA) groups, the synthesis of which is catalyzed in part by the enzyme EptA. Inactivation of EptA increases bacterial sensitivity to defensins, suggesting that the PEA groups prevent defensin attachment to the bacterial surface. In an effort to better characterize this enzyme the Vrielink group has determined the three dimensional structure of the EptA enzyme. These structural studies are being correlated with functional studies carried out in Prof Kahler’s laboratory. Together with Assoc Prof Stubbs and Prof Scanlon fragment screening and inhibitor design studies are being undertaken as steps towards development of novel antivirulence therapeutics to treat multidrug resistance in bacteria.

• Mesothelioma is a fatal cancer of the lungs, caused by asbestos. Western Australia has one of the highest rates of this cancer in the world, because of the mining, transport and high use of asbestos. Mesothelioma starts in the lining of the lungs, but once it is diagnosed it often rapidly grows into the heart and ribcage. This causes severe shortness of breath and pain. The fast growth into surrounding organs makes it an ‘invasive’ cancer. Our collaborator on this project, Assoc. Prof Lesterhuis, has recently identified two metabolic transcription factors that are involved in mesothelioma pathology. Antagonists of these proteins kill mesothelioma cells selectively over normal cells. This suggests that these proteins are excellent targets for developing an anticancer drug to treat mesothelioma with high specificity.  In collaboration with Assoc. Profs Matthew Piggott and Willem Lesterhuis (UWA), work is being carried out on the development of antagonists to to these transcription factors as potential novel therapeutic agents to treat mesothelioma cancer.

• Mitochondria and chloroplasts are organelles that contain their own genomes.  In order to transcribe and translate their genes within the membrane encapsulated organelle they require the transport of tRNAs from the cell cytoplasm to the mitochdondrial matrix. Our collaborator, Monika Murcha, has discovered a mitochondrial outer membrane protein required for the uptake of tRNA into mitochondria.  This protein, called Tric 1 (tRNA import component) has the ability to bind tRNA via the RNA binding domain (SAM).  Our pastcrystallographic studies on the SAM domain suggests that the full length protein, Tric1, forms an oligomeric entity required for movement of tRNA across the mitochondrial membrane.  Currently our studies are focussed on characterising the molecular structure of the full length Tric1 using cryogenic electron microscopy and X-ray crystallography methods.

• In collaboration with Dr. Flora Meilleur (Oak Ridge National Laboratory) neutron crystallography studies are being undertaken on the flavoenzyme, cholesterol oxidase. These studies are directed at understanding the redox activity of the enzyme through characterizing the positions of hydrogen atoms within the protein during the catalytic cycle.

• Many pathogenic bacteria possess polysaccharide capsule structures on their exterior surface which aids in disease progression. Different bacterial serogroups have varied capsule structures which are the target forvaccine development. The molecular building blocks of of the capsules are synthesised within the bacterial cell before being exported to the exterior surface of the microorganism. A large molecular machinery composed of four different proteins is involved in the export of these complex molecules across two bacterial membranes. The Vrielink group is determining the molecular structures of the capsule transport machinery using the methods of crystallography and cryo Electron Microscopy.  These studies will provide insights into the mechanism of the large and complex polysaccharide molecules' transport across membranes.