The design of targetable epigenetic modifiers. The project aims to engineer enzymes as valuable tools for understanding gene expression mechanisms and potentially a technology for altering gene expression in plants, animals or humans in a targetable manner. The genetic information encoded in the DNA of all complex organisms has been shown to be augmented by decorations on both DNA and the histone proteins that package DNA. This so-called epigenetic information is important but not well understoo ....The design of targetable epigenetic modifiers. The project aims to engineer enzymes as valuable tools for understanding gene expression mechanisms and potentially a technology for altering gene expression in plants, animals or humans in a targetable manner. The genetic information encoded in the DNA of all complex organisms has been shown to be augmented by decorations on both DNA and the histone proteins that package DNA. This so-called epigenetic information is important but not well understood. The project plans to design highly specific and targetable enzymes that can interrogate and manipulate epigenetic information in living cells. Understanding the regulation of gene expression and controlling the expression of chosen genes may form a foundation for applications in agriculture, biology and medicine.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
Exploring the catalytic role of the Rubisco small subunit: a new target for improving carbon dioxide-fixation in plants. This project uses new biotechnological tools to improve the performance of the photosynthetic protein Rubisco, the primary carbon dioxide-fixing enzyme in plants. By supercharging photosynthesis, this research will help to boost yield and reduce water and nitrogen use in crops.
Rubisco for all climates: unlocking the enzyme's structure-function relations for more efficient photosynthesis. This projects biotechnological research will identify structural features in the carbon dioxide (CO2)-capturing enzyme from plants that improve its performance, particularly at warmer temperatures. This knowledge is vital for predicting the influence of climate change on crop productivity and paving the way for supercharging photosynthesis to boost crop performance.
Structure-based inhibitor design of VAP-1/SSAO for the treatment of respiratory dirsorders and other major inflammatory diseases. Inflammatory diseases, such as asthma, rheumatoid arthritis and multiple sclerosis, are widespread and often poorly treated in Australia and elsewhere. Inhibitors of the recently studied VAP-1/SSAO protein are predicted to effectively treat the inflammation symptoms of one or more of these diseases. A structure-based approach to discover these new medicines should pro ....Structure-based inhibitor design of VAP-1/SSAO for the treatment of respiratory dirsorders and other major inflammatory diseases. Inflammatory diseases, such as asthma, rheumatoid arthritis and multiple sclerosis, are widespread and often poorly treated in Australia and elsewhere. Inhibitors of the recently studied VAP-1/SSAO protein are predicted to effectively treat the inflammation symptoms of one or more of these diseases. A structure-based approach to discover these new medicines should provide a means to identify patentable compounds, with high potency, efficacy and safety. If this approach is successful, an Australian pharmaceutical company will be one of the first to the market with this new medicine to treat these chronic diseases.Read moreRead less
Biosynthetic LEGO: enzymatic redesign to produce new vancomycin analogues. This project aims to uncover the reengineering potential of the biosynthetic machinery that produces glycopeptide antibiotics by advancing our understanding of how the core peptide production line functions. Natural product biosynthesis often produces complex peptide structures, with one important example being the glycopeptide antibiotics. This project expects to generate new knowledge about enzymatic peptide biosynthesi ....Biosynthetic LEGO: enzymatic redesign to produce new vancomycin analogues. This project aims to uncover the reengineering potential of the biosynthetic machinery that produces glycopeptide antibiotics by advancing our understanding of how the core peptide production line functions. Natural product biosynthesis often produces complex peptide structures, with one important example being the glycopeptide antibiotics. This project expects to generate new knowledge about enzymatic peptide biosynthesis using a highly interdisciplinary approach and previously developed tools. The anticipated outcomes of this project will be an enhanced understanding of how such complex peptide biosynthesis is performed, which is knowledge vital for future efforts to reengineer such biosynthetic peptide assembly lines as a series of modular LEGO blocks to produce new bioactive peptides.Read moreRead less
Defining peptide structure and function: the shape of things to come. In this project we develop new and general ways of chemically defining the structure and function of natural peptides. This then provides a basis of potential therapies to treat a number of diseases currently confronting Australia's aging population, for example, cataract, Alzheimer's disease, cancer, and cardiovascular disease.
Understanding the mechanisms of peptide cyclisation. This project aims to identify, study, engineer and apply a new class of biocatalysts (called asparaginyl endopeptidase enzymes) as versatile tools for manufacturing of advanced therapeutics and bio-insecticides. The expected outcomes include fundamental new knowledge on the mechanism of action of these catalysts, an expanded toolbox for precision engineering of biomolecules and new strategies for production of high-value pharmaceuticals and cr ....Understanding the mechanisms of peptide cyclisation. This project aims to identify, study, engineer and apply a new class of biocatalysts (called asparaginyl endopeptidase enzymes) as versatile tools for manufacturing of advanced therapeutics and bio-insecticides. The expected outcomes include fundamental new knowledge on the mechanism of action of these catalysts, an expanded toolbox for precision engineering of biomolecules and new strategies for production of high-value pharmaceuticals and crop protecting agents. The project is significant because it will contribute to high value biotechnology and agricultural industries in Australia, with the potential for economic, environmental, training and societal benefits.Read moreRead less
Characterisation of plant cysteine proteases with therapeutic potential. This project aims to uncover how plant enzymes have effects on the immune system. This will allow the development of these enzymes as therapeutic agents for cancer and autoimmune conditions.
In vitro expression of macrocyclic peptides. This project aims to develop a novel strategy for the production of polypeptides with unnatural chemical groups using a sense codon reassignment approach. Novel peptides could be used in a range of pharmaceutical applications. Peptides made of 20 natural amino acids cover only a very small fraction of the available chemical and functional space. While a peptide’s functionality can be extended with unnatural amino acids, the methods for their site-sele ....In vitro expression of macrocyclic peptides. This project aims to develop a novel strategy for the production of polypeptides with unnatural chemical groups using a sense codon reassignment approach. Novel peptides could be used in a range of pharmaceutical applications. Peptides made of 20 natural amino acids cover only a very small fraction of the available chemical and functional space. While a peptide’s functionality can be extended with unnatural amino acids, the methods for their site-selective incorporation are inefficient. The project’s strategy relies on the depletion of selected tRNAs from an in vitro protein translation system and their replacement with synthetic tRNAs, charged with unnatural amino acids. It is expected that the developed technology could be used to rapidly generate and screen highly diversified macrocyclic peptide libraries.Read moreRead less