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Linkage Infrastructure, Equipment And Facilities - Grant ID: LE0561041
Funder
Australian Research Council
Funding Amount
$347,358.00
Summary
A New Generation Biosensor and Fluorescence Facility for Proteomics. The complete DNA sequence (the genome) is now known for many organisms and advances are being made to identify the complement of messenger RNA (the transcriptome) and the resultant collection of proteins (the proteome). The genome is largely fixed while the transcriptome and proteome differ between cell types in an organism and constantly vary to adapt the cell to changing conditions. The mediators of these variations are prote ....A New Generation Biosensor and Fluorescence Facility for Proteomics. The complete DNA sequence (the genome) is now known for many organisms and advances are being made to identify the complement of messenger RNA (the transcriptome) and the resultant collection of proteins (the proteome). The genome is largely fixed while the transcriptome and proteome differ between cell types in an organism and constantly vary to adapt the cell to changing conditions. The mediators of these variations are proteins, interacting with each other and with signal molecules. The next frontier in molecular biology is to identify and quantify these protein interactions. Our two institutions have a very large cohort of biologists whose research on proteins would be greatly facilitated by the Biacore 3000 and the ISS K2.Read moreRead less
Understanding mechanistic and systemic regulation of protein prenyltransferases. The proposed research will expand our understanding of lipid-conjugating enzymes that are critical for a multitude of normal cellular functions. We seek to reveal the basic workings of cells and help to explain the development and complexity of signalling networks in eukaryotic evolution. The findings will enable us to explore and exploit the catalytic properties of these lipid-related enzymes for applications in bi ....Understanding mechanistic and systemic regulation of protein prenyltransferases. The proposed research will expand our understanding of lipid-conjugating enzymes that are critical for a multitude of normal cellular functions. We seek to reveal the basic workings of cells and help to explain the development and complexity of signalling networks in eukaryotic evolution. The findings will enable us to explore and exploit the catalytic properties of these lipid-related enzymes for applications in biotechnology. The ultimate aim is to create novel technologies for protein production, modification and analysis that will accelerate the pace of discovery in protein research, basic cell and organism biology, diagnostics, biotechnology and drug discovery. Read moreRead less
The LINK to Regulating Lysine Levels in Wheat. This project aims to characterise a recently discovered allosteric mechanism called 'Ligand-Induced association by Lysine (K)' (LINK) model. LINK model regulates the function of a key biosynthetic enzyme in bacteria and plants, including agriculturally-important species such as wheat. Also, it represents a highly significant discovery to the field of biochemistry. The expected outcomes of this project include an in-depth understanding of the molecul ....The LINK to Regulating Lysine Levels in Wheat. This project aims to characterise a recently discovered allosteric mechanism called 'Ligand-Induced association by Lysine (K)' (LINK) model. LINK model regulates the function of a key biosynthetic enzyme in bacteria and plants, including agriculturally-important species such as wheat. Also, it represents a highly significant discovery to the field of biochemistry. The expected outcomes of this project include an in-depth understanding of the molecular basis of a new allosteric mechanism for regulating intracellular lysine levels, which in the longer term offers excellent potential to be manipulated for agricultural benefits.Read moreRead less
Biosynthesis of nonribosomal peptide toxins in cyanobacteria: A functional characterisation of microcystin synthetase. Microcystins are potent toxins and tumour promoters produced by cyanobacteria associated with blue-green algal blooms. This non-ribosomal peptide is produced by microcystin synthetase, a unique enzyme complex comprised of peptide synthetases, polyketide synthases, and integrated accessory enzymes. We have identified and characterised the extensive gene cluster encoding this enzy ....Biosynthesis of nonribosomal peptide toxins in cyanobacteria: A functional characterisation of microcystin synthetase. Microcystins are potent toxins and tumour promoters produced by cyanobacteria associated with blue-green algal blooms. This non-ribosomal peptide is produced by microcystin synthetase, a unique enzyme complex comprised of peptide synthetases, polyketide synthases, and integrated accessory enzymes. We have identified and characterised the extensive gene cluster encoding this enzyme. This project describes the biochemical characterisation of specific enzyme activities within microcystin synthetase and how they determine the final structure and toxicity of the many forms of microcystin. Interactions between this enzyme complex and its substrate amino acids will provide information for the genetic engineering of this and similar natural products.Read moreRead less
The regulation of signalling molecules in Saccharomyces Cerevisiae by inositol polyphosphate 5-phosphatases. Phosphoinositide signalling molecules regulate the actin cytoskeleton, secretion, vesicular trafficking and cell growth and death. We have identified, cloned and characterised a family of signal terminating enzymes called inositol polyphosphate 5-phosphatases (5-phosphatases) that regulate phosphoinositide signalling molecules. We have cloned and characterised four distinct 5-phosphatases ....The regulation of signalling molecules in Saccharomyces Cerevisiae by inositol polyphosphate 5-phosphatases. Phosphoinositide signalling molecules regulate the actin cytoskeleton, secretion, vesicular trafficking and cell growth and death. We have identified, cloned and characterised a family of signal terminating enzymes called inositol polyphosphate 5-phosphatases (5-phosphatases) that regulate phosphoinositide signalling molecules. We have cloned and characterised four distinct 5-phosphatases in the yeast Saccharomyces Cerevisiae and demonstrated by both deletion and overexpression studies that these enzymes regulate the actin cytoskeleton, endocytosis and secretion. This research proposal aims to investigate the signalling complexes the 5-phosphatases form with specific actin binding and or regulatory proteins, investigate the complex interactions of phosphoinositide lipid phosphatases and the roles they play in regulating secretion from the endoplasmic reticulum and finally characterize a novel 5-phosphatase that we have recently identified. Collectively the outcome of these studies will provide novel information about the functionallly significant signalling pathways regulated by this important enzyme family.Read moreRead less
Synthesis of substrate analogues for probing catalytic mechanisms and specificity of enzymes involved in the metabolism of plant polysaccharides. The project is aimed at strengthening collaborations between research groups in Adelaide and France, with the specific objective of synthesizing substrate analogues as probes of enzymatic mechanisms and substrate specificity in polysaccharide hydrolases and synthases of barley. The chemical expertise resides in France, while the enzymatic work will be ....Synthesis of substrate analogues for probing catalytic mechanisms and specificity of enzymes involved in the metabolism of plant polysaccharides. The project is aimed at strengthening collaborations between research groups in Adelaide and France, with the specific objective of synthesizing substrate analogues as probes of enzymatic mechanisms and substrate specificity in polysaccharide hydrolases and synthases of barley. The chemical expertise resides in France, while the enzymatic work will be conducted largely in Australia. Exchange of research staff, particularly at the postgraduate student and research associate levels, is considered essential to capture the benefits of the complementary expertise and to extend an existing international collaboration. The target enzymes are of central importance in cell wall metabolism during development of higher plants.Read moreRead less
Dissociation of a Tetrameric Enzyme with Interface-Targeted Peptides. With antibiotic resistance on the rise, there is an urgent need to develop new antibiotics and an equally urgent need to characterise new antibiotic targets. One such target is dihydrodipicolinate synthase (DHDPS) which catalyses the critical step in lysine and cell wall biosynthesis in bacteria. This proposal aims to generate new drugs targeting DHDPS for effective and rapid treatment of bacterial infections, including gastro ....Dissociation of a Tetrameric Enzyme with Interface-Targeted Peptides. With antibiotic resistance on the rise, there is an urgent need to develop new antibiotics and an equally urgent need to characterise new antibiotic targets. One such target is dihydrodipicolinate synthase (DHDPS) which catalyses the critical step in lysine and cell wall biosynthesis in bacteria. This proposal aims to generate new drugs targeting DHDPS for effective and rapid treatment of bacterial infections, including gastroenteritis. Recent statistics show that over 5 million Australians suffer from gastroenteritis each year and hospitalisation for this infection is nearly seven times higher for indigenous than non-indigenous children. Accordingly, this research has the potential to assure a healthier future for millions of Australians.Read moreRead less
Special Research Initiatives - Grant ID: SR0354892
Funder
Australian Research Council
Funding Amount
$40,000.00
Summary
The Australian Protease Network. Proteases are pivotal enzymes during birth, life, ageing and death of all organisms. Proteases regulate most physiological processes by controlling protein activation, synthesis and turnover and are essential for replication and spread of viruses, bacteria and parasites that cause infectious diseases. Blockbuster drugs and diagnostics already target a few proteases. Australians have made innovative contributions individually to understanding and regulating these ....The Australian Protease Network. Proteases are pivotal enzymes during birth, life, ageing and death of all organisms. Proteases regulate most physiological processes by controlling protein activation, synthesis and turnover and are essential for replication and spread of viruses, bacteria and parasites that cause infectious diseases. Blockbuster drugs and diagnostics already target a few proteases. Australians have made innovative contributions individually to understanding and regulating these enzymes. However this initiative aims to network their efforts by value-adding to the current protease research through promoting national and international collaborations to improve our understanding of biology, and encourage exploitation of proteases/inhibitors/receptors for pharmaceutical and industrial applications.Read moreRead less
Enantioselective nitrilases from filamentous fungi. The optical characteristics (chirality) of chemical precursors are important for many fine chemicals. Chiral intermediates are in high demand by the pharmaceutical and agrochemical industries for the preparation of bulk drug intermediates and agricultural products. Nitriles are attractive starting points but their conversion to corresponding amides and carboxylic acids generates significant wastes. Their hydrolysis can be performed under mil ....Enantioselective nitrilases from filamentous fungi. The optical characteristics (chirality) of chemical precursors are important for many fine chemicals. Chiral intermediates are in high demand by the pharmaceutical and agrochemical industries for the preparation of bulk drug intermediates and agricultural products. Nitriles are attractive starting points but their conversion to corresponding amides and carboxylic acids generates significant wastes. Their hydrolysis can be performed under mild conditions by enzymes termed nitrilases. We will work on fungal nitrilases as they present a globally attractive, yet untapped commercial target. The outcome for Applimex will be a suite of biocatalysts specific for the production of key intermediates for drug and agrochemical syntheses.Read moreRead less
Probing JNK MAPK function with peptide inhibitors. It has generally been accepted that the JNK MAPK family of protein kinases is rapidly and potently activated following the exposure of mammalian cells to stresses and cytokines. However, their biological role has remained controversial. We believe that this problem reflects the lack of a generally applicable and specific JNK MAPK inhibitor. In this project we continue our characterisation of a small peptide inhibitor developed in our laboratori ....Probing JNK MAPK function with peptide inhibitors. It has generally been accepted that the JNK MAPK family of protein kinases is rapidly and potently activated following the exposure of mammalian cells to stresses and cytokines. However, their biological role has remained controversial. We believe that this problem reflects the lack of a generally applicable and specific JNK MAPK inhibitor. In this project we continue our characterisation of a small peptide inhibitor developed in our laboratories. We aim to determine its mechanism of inhibition, the specificity of interaction, and to evolve more effective inhibitors. With these new inhibitors, we can effectively address the biological roles of these kinases.Read moreRead less