Dr W. Bret Church
BSc (Hons) DipEd PhD
Senior Lecturer
A15 - Pharmacy And Bank Building
The University of Sydney
| Telephone | +61 2 9036 6569 |
| Fax | +61 2 9351 4391 |
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Biographical details
Dr Bret Church joined the Faculty of Pharmacy at the University in 2005, and has a research group with interest in protein-drug interactions, specifically with interest in targets in cancer, diabetes and schizophrenia. He is part of a Group in Biomolecular Structure and Informatics.He has over 25 years experience in research in the fields of crystallography, computational drug design and bioinformatics.
Dr Church completed a PhD at the University of Sydney working on a blue copper protein, with time spent at Brookhaven National Laboratory, New York. He was then appointed a Alberta Heritage Fund for Medical Research post-doctoral fellow in the Department of Biochemistry at the University of Alberta, Edmonton, Canada, working on target proteins, including lysosomal storage disease. He spent three years in the biotechnology industry in California, before returning to Australia.
Dr Church established a molecular modelling laboratory at the Garvan Institute for Medical Research where he continued studies of computational drug design in the neurosciences and in inflammation. In 2001 he began his academic career and was part of a team to establish Molecular Biotechnology at the University of Sydney.
His research work has been supported by the Australian Research Council, National Health and Medical Research Council of Australia, Australian Synchrotron, Australian Institute of Nuclear Science and Engineering, Rebecca Cooper Foundation for Medical Research, and others.
Research interests
My interests are in structure-based drug design and particularly the use of biophysical techniques, structural biology and structural bioinformatics to help understand the relationships between drug targets and drugs to be applied to drug discovery.
Abnormal levels of kynurenic acid (KA) have been thought to accompany several neuropsychiatric diseases, especially schizophrenia. This is consistent with the role of KA as an antagonist acting at the glutamate-binding site of the N-methyl D-aspartic acid receptor. Production of this metabolite by kynurenine aminotransferases could contribute to pathophysiology of psychoses, making the kynurenine pathway a valuable target for the treatment of such diseases. On this basis, novel inhibitors of the human kynurenine aminotransferases will be valuable, and we have been pursuing their design.
Over 700 depositions to the data bank holding protein structures are made every month. Each entry may be a new structure, a structure with a new inhibitor or a mutant. These structures are providing more data in the quest for realistic assessments of molecular recognition and interaction, which are the basis for all cellular processes, and therefore of great interest for studies in therapeutic intervention. We are interested in the analysis of available protein structures to further prediction methods. Of great importance have been recent protein structures such as the adrenergic, dopamine and histamine receptors, representing the first of the highly resolved G-protein coupled receptor structures. Areas of specific interest are the G-protein coupled receptors, but also other membrane-bound targets. With an understanding of genomic sequencing, automated tools may be a way to expedite the pipeline directly from the potential drug targets to the discovery of drug candidates.
Abnormal levels of kynurenic acid (KA) have been thought to accompany several neuropsychiatric diseases, especially schizophrenia. This is consistent with the role of KA as an antagonist acting at the glutamate-binding site of the N-methyl D-aspartic acid receptor. Production of this metabolite by kynurenine aminotransferases could contribute to pathophysiology of psychoses, making the kynurenine pathway a valuable target for the treatment of such diseases. On this basis, novel inhibitors of the human kynurenine aminotransferases will be valuable, and we have been pursuing their design.
Over 700 depositions to the data bank holding protein structures are made every month. Each entry may be a new structure, a structure with a new inhibitor or a mutant. These structures are providing more data in the quest for realistic assessments of molecular recognition and interaction, which are the basis for all cellular processes, and therefore of great interest for studies in therapeutic intervention. We are interested in the analysis of available protein structures to further prediction methods. Of great importance have been recent protein structures such as the adrenergic, dopamine and histamine receptors, representing the first of the highly resolved G-protein coupled receptor structures. Areas of specific interest are the G-protein coupled receptors, but also other membrane-bound targets. With an understanding of genomic sequencing, automated tools may be a way to expedite the pipeline directly from the potential drug targets to the discovery of drug candidates.
Selected grants
2013
- A Research Platform for exploring the Genotype - Phenotype Nexus; Waterhouse P, Church W, Firth N, Harry E; Australian Research Council (ARC)/Linkage Infrastructure, Equipment and Facilities (LIEF).
- Perpetual Synchrotron Travel Grants Account for Dr W.Bret Church; Church W; Australian Synchrotron Company Limited/Funding Application for Interstate User Groups.
2012
- The solution structure of HAMLET: deterated alpha-lactalbumin in complex with hydrogenated oleic acid; Church W; Australian Institute of Nuclear Science and Engineering/Access to Facilities and/or Services.
2011
- automated storage, retrieval, and UV imaging system; Jormakka M, Gamble J, Semsarian C, Rasko J, Vadas M, Xia P, Gorrell M, Clarke R, Holst J, Church W; National Health and Medical Research Council/Equipment Grants.
2009
- Bruker APEX II CCD Detector Fourth Generation APEX II ultra-low noise CCD X-ray detector with 16 megapixel chip; Hibbs D, Roufogalis B, Murray M, Hambley T, Hanrahan J, Church W, Collins (Chebib) M, Johnston G, Young P, Traini D; National Health and Medical Research Council/Equipment Grants.
2003
- Automated analysis of the 2D and 3D structural properties of membrane spanning proteins using a novel sequence-independent method; Church W; University of Sydney (Sesqui)/Bridging Support.
- Detection of proetrin functional structural motifs for genomics; Church W; University of Sydney (Sesqui)/New Staff Support Scheme.
Selected publications
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PhD and master's project opportunities
- Medicinal and Pharmaceutical Chemistry — Design, Synthesis and Testing of New Anti-Bacterial Agents
- Structure-based drug design with Kynurenine Aminotransferase-I
- Informatics and Bioinformatics-based Approaches to Protein-Ligand Interaction
- Structure-based drug design with Soluble Epoxide Hydrolase
- Understanding the Switch between Enzyme and Signaling Behaviours in Human Group IIA Secreted Phospholipase A2 by Inhibitory Intervention