Validating protozoa-specific drug targets using peptides from biodiverse gene fragment libraries. Cryptosporidium and the trypanosomes are protozoan parasites, which have a global impact on the health, survival and economic development of millions of people and animals world wide. New therapies for the diseases they cause are urgently required. We describe a novel means of identifying protozoa-specific peptides that will inhibit the formation of essential protein complexes, which have no effect ....Validating protozoa-specific drug targets using peptides from biodiverse gene fragment libraries. Cryptosporidium and the trypanosomes are protozoan parasites, which have a global impact on the health, survival and economic development of millions of people and animals world wide. New therapies for the diseases they cause are urgently required. We describe a novel means of identifying protozoa-specific peptides that will inhibit the formation of essential protein complexes, which have no effect on the mammalian host. Candidate peptides will then be used to validate these protein complexes as new targets for the development of peptide-based therapeutic compounds. This project will validate novel targets for the development of new treatments for these diseases.Read moreRead less
Specific gene inhibition through functional genomics and high through-put small molecule screening. This project will utilise functional genomic technologies in an attempt to identify genes in childhood neuroblastoma as potential candidates for the future development of molecular-targeted gene therapy. By screening large 'libraries' of chemical compounds, we aim to identify compounds with the ability to specifically inhibit these gene targets. This project will therefore define novel molecular t ....Specific gene inhibition through functional genomics and high through-put small molecule screening. This project will utilise functional genomic technologies in an attempt to identify genes in childhood neuroblastoma as potential candidates for the future development of molecular-targeted gene therapy. By screening large 'libraries' of chemical compounds, we aim to identify compounds with the ability to specifically inhibit these gene targets. This project will therefore define novel molecular targets and possibly facilitate the future development of new therapeutic approaches to treating neuroblastoma. In addition, the project will develop know-how that can be utilised by both the industry partner and the broader research community and will introduce to Australian science novel techniques and skills. Read moreRead less
Expression and characterisation of nutrient transporters from the intracellular malaria parasite, Plasmodium falciparum. The malaria parasite invades the red blood cells of its host and this provides it with a safe haven in which to grow and replicate. Within the red blood cell, the parasite takes up nutrients and excretes metabolic wastes via specialised membrane transport proteins which are, as yet, very poorly understood. The sequencing of the malaria parasite genome has enabled us to ident ....Expression and characterisation of nutrient transporters from the intracellular malaria parasite, Plasmodium falciparum. The malaria parasite invades the red blood cells of its host and this provides it with a safe haven in which to grow and replicate. Within the red blood cell, the parasite takes up nutrients and excretes metabolic wastes via specialised membrane transport proteins which are, as yet, very poorly understood. The sequencing of the malaria parasite genome has enabled us to identify candidates for a wide variety of these proteins. The aim of this project is to establish systems in which the functional properties of these transporter proteins may be characterised in detail.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE0236372
Funder
Australian Research Council
Funding Amount
$100,000.00
Summary
CENTRIFUGATION FACILITIES FOR THE GENETICS ANALYSIS FACILITY. Access to both a high-speed centrifuge and an ultracentrifuge is essential for a wide range of biochemistry and molecular biology research projects. A high-speed centrifuge is essential for the collection of bacteria cultured to express specific proteins as well as the collection of purified proteins isolated from a wide range of organisms. Similarly an ultracentrifuge is required for the isolation of viruses and the preparation and p ....CENTRIFUGATION FACILITIES FOR THE GENETICS ANALYSIS FACILITY. Access to both a high-speed centrifuge and an ultracentrifuge is essential for a wide range of biochemistry and molecular biology research projects. A high-speed centrifuge is essential for the collection of bacteria cultured to express specific proteins as well as the collection of purified proteins isolated from a wide range of organisms. Similarly an ultracentrifuge is required for the isolation of viruses and the preparation and purification of RNA and DNA. The two machines will facilitate the continuation of research projects funded by both government and industry grants. The centrifuges will complement the equipment available in the Genetic Analysis Facility.Read moreRead less
Enhanced biocatalysis in organic solvents for pharmaceutical biotransformation. Enzymes such as hydrolases play an important role in biotechnology because of their extreme versatility with respect to substrate specificity and stereoselectivity. The use of lipases as catalysts for optical isomer-specific organic reactions is often limited by unacceptably low enantioselectivities. We will investigate recombinant enzymes cloned from thermophilic lipolytic bacteria for synthetic reactions in orga ....Enhanced biocatalysis in organic solvents for pharmaceutical biotransformation. Enzymes such as hydrolases play an important role in biotechnology because of their extreme versatility with respect to substrate specificity and stereoselectivity. The use of lipases as catalysts for optical isomer-specific organic reactions is often limited by unacceptably low enantioselectivities. We will investigate recombinant enzymes cloned from thermophilic lipolytic bacteria for synthetic reactions in organic solvents, especially chiral resolution of mixtures in the production of pharmaceutical intermediates. Genetic improvement of lipase enantiospecificity and regioselectivity will be achieved using in vitro evolution by recombination and screening. The outcome will be cost-effective production superior biocatalysts with specifically enhanced regiospecific, enantioselective and hydrolytic characteristics.
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Circular Plant Proteins with Pharmaceutical Applications. The proposed research will develop methods for using plants as protein production factories. Initially I will use plants to create engineered cyclotides that incorporate peptides with proven therapeutic activity against cancer and multiple sclerosis. Successful production of therapeutic proteins in plants will benefit Australians by making treatments for these and other diseases more accessible. It also has the potential for a major econo ....Circular Plant Proteins with Pharmaceutical Applications. The proposed research will develop methods for using plants as protein production factories. Initially I will use plants to create engineered cyclotides that incorporate peptides with proven therapeutic activity against cancer and multiple sclerosis. Successful production of therapeutic proteins in plants will benefit Australians by making treatments for these and other diseases more accessible. It also has the potential for a major economic benefit from the sales of Australian-based drugs. This proposal will also provide outstanding research training for graduate students in multidisciplinary methods that constitute state-of the-art structural and plant molecular biology.Read moreRead less
Conantokin selectivity for heteromeric N-methyl-D-aspartate (NMDA) receptors. NMDA receptors are ligand gated ion channels formed by heterogeneous population of subunits with distinct pharmacological and biophysical properties. The heterogeneic receptors are differentially expressed during development and play an important role in many physiological and pathological processes. Conantokins are toxins isolated from Conus venoms, which target NMDA receptor subunits with high affinity. The primary g ....Conantokin selectivity for heteromeric N-methyl-D-aspartate (NMDA) receptors. NMDA receptors are ligand gated ion channels formed by heterogeneous population of subunits with distinct pharmacological and biophysical properties. The heterogeneic receptors are differentially expressed during development and play an important role in many physiological and pathological processes. Conantokins are toxins isolated from Conus venoms, which target NMDA receptor subunits with high affinity. The primary goal of this study is to examine the effects of conantokins on the molecular properties of different NMDA receptor subtypes in vivo and in vitro.Read moreRead less
New Methods for Directed Molecular Evolution of Novel Protein Functions. Novel ribosome-based techniques can be used to carry out test-tube evolution of proteins with new structures and functions. The methods rely on (a) physical association of individual nucleic acid molecules with the particular protein molecules they encode, (b) selection of proteins with new functions, and (c) recovery of the attached genetic code. This project will address several issues that currently limit use of these fr ....New Methods for Directed Molecular Evolution of Novel Protein Functions. Novel ribosome-based techniques can be used to carry out test-tube evolution of proteins with new structures and functions. The methods rely on (a) physical association of individual nucleic acid molecules with the particular protein molecules they encode, (b) selection of proteins with new functions, and (c) recovery of the attached genetic code. This project will address several issues that currently limit use of these frontier technologies for evolution of new protein products that have a wide range of practical applications.Read moreRead less
How organisms coordinate energy supply and demand. The metabolic stress sensing protein kinase called the AMP activated protein kinase controls metabolism of all eukaryotes to meet the needs of energy demand and nutrient supply. It is responsible for accelerating metabolism (glucose transport, glycolysis and fatty acid oxidation) in response to energy demand and with caloric restriction it regulates gene transcription to adapt to energy supply. This project is to provide a comprehensive unders ....How organisms coordinate energy supply and demand. The metabolic stress sensing protein kinase called the AMP activated protein kinase controls metabolism of all eukaryotes to meet the needs of energy demand and nutrient supply. It is responsible for accelerating metabolism (glucose transport, glycolysis and fatty acid oxidation) in response to energy demand and with caloric restriction it regulates gene transcription to adapt to energy supply. This project is to provide a comprehensive understanding of the AMP activated protein kinase (enzyme isoforms, genes, physiological roles and regulation). This knowledge will have major benefits in biopharmaceutical development, the livestock, plant and sport/racing industries.Read moreRead less