About Dr W Bret Church

My research is about bringing systematic methodologies to drug discovery based on the principles of a protein target’s structure and ligand binding, with specific projects in the area of Cancer, Cardiovascular Disease, Inflammation and Psychoses such as in schizophrenia.

Dr Church is interested in proteins and particularly in how the three-dimensional structure of proteins confers their function. This extends to fields as crystallography, small angle scattering, structural bioinformatics, and the use of molecular biology to express proteins for their study including their crystallization. Importantly this is all out together with implications for the design and of novel drugs, or improvements in lead compounds.

Dr Church is widely known in the fields of protein structure and protein structure prediction and has made important contributions in recent years. He has made major contributions to structural biology, having studied and crystallised many proteins, performing both neutron and X-ray single crystal diffraction techniques in home, synchrotron and reactor facilities. In his postdoctoral experience he sent experiments into space. He spent 3 years in industry (Biosym Technologies, CA, USA, 1992-1995), and it was while there he was an inaugural contributing homology modeller to the successful CASP Meeting (Critical Assessment of Protein Structure Prediction) which have provided a platform to benchmark protein structure prediction methods. His approach and that of Biosym, was more successful than MODELLER, a program which subsequently has had much acclaim. He has developed a modelling methodology for analysing and predicting the 2D and 3D structural features of integral membrane proteins and more recently, software for visualisation and annotation of alternative splice variants. His work appears in significant journals such as Proteins, Journal of Molecular Biology and the Journal of Biological Chemistry. He helped establish the structural biology and modelling facilities at the Garvan Institute/Victor Chang (1998-2000), and made significant contributions to several projects within these Institutes, resulting in important perspectives on the function of key proteins, most notably G-protein coupled receptors. He then helped establish the Molecular Biotechnology Program as Senior Lecturer at the University of Sydney (2001-4). He now is Senior Lecturer in Pharmacy, and is in a Group in Biomolecular Structure and Informatics.

Most recently, Dr Church has spoken in locations as China, Hong Kong and Iran but has presented at a number of conferences and locations around the world. He has been active in the Sydney Protein Group, the Biomolecular Division of the Royal Australian Chemical Institute and the Association of Molecular Modellers of Australasia, and has organised numerous meetings which have brought prominent contributors to the field to Sydney and Australia. In 2003 he received the Selby Award at Sydney University for a beginning academic, and early on was awarded an Alberta Heritage Foundation for Medical Research Fellowship to post-doc at the University of Alberta, Edmonton, Canada.

Selected publications

1. Rath, E., Cheng, Y., Pinese, M., Sarun, K., Hudson, A., Weir, C., Wang, Y., Hakansson, A., Howell, V., Liu, G., Reid, G., Church, W.B. (2018). BAMLET kills chemotherapy-resistant mesothelioma cells, holding oleic acid in an activated cytotoxic state. PloS One, 1-32.

2. Jayawickrama, G., Nematollahi, A., Sun, G., Church, W.B. (2018). Fragment Screening of Human Kynurenine Aminotransferase-II. SLAS Disc, 23, 511-519.

3. Nematollahi, A., Sun, G., Jayawickrama, G., Hanrahan, J., Church, W.B. (2017). Crystal structure and mechanistic analysis of a novel human kynurenine aminotransferase-2 reversible inhibitor. Med. Chem. Rese, 26, 2514-2519. 

4. Nadvi, N., Salam, N., Park, J., Akladios, F., Kapoor, V., Collyer, C., Gorrell, M., Church, W.B. (2017). High resolution crystal structures of human kynurenine aminotransferase-I bound to PLP cofactor, and in complex with aminooxyacetate. Prot Sci, 26, 727-736. 

 5. Jayawickrama, G., Nematollahi, A., Sun, G., Gorrell, M., Church, W.B. (2017). Inhibition of human kynurenine aminotransferase isozymes by estrogen and its derivatives. Sci Rep, 7, 1-11. 

 6. Kim, R., Malde, A., Nematollahi, A., Scott, K., Church, W. (2017). Molecular dynamics simulations reveal structural insights into inhibitor binding modes and functionality in human Group IIA phospholipase A2. Proteins, 85, 827-842.

7. Rath, E., Duff, A., Gilbert, E., Doherty, G., Knott, R., Church, W.B. (2017). Neutron scattering shows a droplet of oleic acid at the center of the BAMLET complex. Proteins, 85, 1371-1378.

8. Sun, G., Nematollahi, A., Nadvi, N., Kwan, A., Jeffries, C., Church, W.B. (2016). Expression, purification and crystallization of human kynurenine aminotransferase 2 exploiting a highly optimized codon set. Prot Exp Purif, 121, 41-45.

9. Kim, E., Rath, E., Tsang, V., Duff, A., Robinson, B., Church, W.B., Benn, D., Dwight, T., Clifton-Bligh, R. (2015). Structural and functional consequences of succinate dehydrogenase subunit B mutations. Endocrine-Related Cancer, 22, 387-397