The Centre for Biodiscovery

The Centre for Biodiscovery

Description

The Centre for Biodiscovery is an interdisciplinary research centre focusing on the discovery and design of biologically active molecules, using natural product and synthetic chemistry and identifying bio molecular activity using cellular and molecular methods in protein technology and proteomics.

Expertise

The Centre for Biodiscovery is an interdisciplinary research centre. The major strengths are drawn from natural products and synthetic chemistry research in the School of Chemistry and Physics and mechanism of action studies and proteomics in the School of Biological Sciences.

Objective

The Centre for Biodiscovery focuses on the discovery and design of biologically active molecules, using natural product and synthetic chemistry and identifying bio molecular activity using cellular and molecular methods in protein technology and proteomics.

Research Focus

Chemical genetics research, proteomics, drug discovery.

Unique Capability Proposition

Victoria is a national leader in proteomics research and is a participant in the international human proteome project. The Centre has close links with a number of areas within the University and is working on projects with several Crown Research Institutes and other research organisations. These projects include the discovery and design of anti-cancer drugs, searches for naturally occurring pest control agents, plant proteins affecting food quality and reactivity, and protein targets for the selection of disease resistance and productivity traits in livestock.

Past Successes

Chemical Genetics Research

Chemical genetics is a discipline that utilizes genetic epistasis to delineate the multigenic networks in which genes operate to effect phenotypes and traits. Epistasis is the combined effect of genes contributing to traits. Techniques now exist to measure it globally in cells that is to say in gene networks of entire genomes. Measurements observe the effects of pairs of knockout mutations, pairs of chemicals acting in lieu of knockouts by ablating gene function or pairs of RNAis to ablate gene function or paired combinations of these perturbations. The technology is based on robotic high–throughput screening of living cells and has a direct spin–off for novel drug discovery. The chemical genetics laboratory is unique in New Zealand. Victoria University has contributed in excess of $1.4M dollars of its own funds in the last 2 years and the Tertiary Education Commission has recently awarded $1.53M in capital and operating funds to Victoria University for chemical genetics

Proteomics

Proteomics is a new technology that uses information gained from sequencing human and other genomes. Victoria is a national leader in this research and is a participant in the international human proteome project. The Centre has close links with a number of areas within the University and is working on projects with several Crown Research Institutes and other research organisations. These projects include the discovery and design of anti–cancer drugs, searches for naturally occurring pest control agents, plant proteins affecting food quality and reactivity, and protein targets for the selection of disease resistance and productivity traits in livestock.

Drug Discovery

Natural Products for Drug Discovery

The objective of this programme is to isolate new secondary metabolites with potential pharmaceutical activity from New Zealand organisms in sufficient quantities for screening in a diverse array of bioassays. The programme is based on an isolation scheme developed at VUW that selects for compounds with drug–like properties and screening by spectroscopy for new chemical entities. Using this approach, we have already isolated a number of new compounds with a wide variety of structures and biological activities. Peloruside A, an anti–mitotic compound isolated from a marine sponge, is an example of a lead compound that is being jointly developed by Victoria University and a US–based biotechnology company (Reata Pharmaceuticals) for use as an anti–cancer agent. Some of the other new compounds are being investigated for the details of their biological activity, for structure activity relationships, and their potential as anticancer agents in various biology and chemistry laboratories.

Design and Synthesis of Natural Product Analogues

This programme involves exploration of synthetic routes to many diverse biologically active natural products and the rational design of novel analogues. This latter aspect complements, and is driven by, the isolation of new secondary metabolites within the Centre for Biodiscovery. Results from the screening of both the natural products and the designed analogues will allow structure–activity analysis and, it is anticipated, improved second–generation analogues.

Cell Biology & Mode of Action of New Natural Products and their Analogs

After an initial screening for bioactivity is carried out on newly isolated natural products, the probable mode of action of the compounds is deduced from preliminary information provided by proteomic analysis, protein/nucleic acid microarrays, and chemical genetics. More detailed characterization of the action of the compounds on their primary and secondary targets is then carried out to determine such properties as binding affinities, selectivities, and potencies. Structurally modified analogues of the lead compounds are also examined to evaluate structure–activity relationships for later pharmacophore modeling.