The design and synthesis of angiotensin converting enzyme-2 (ACE2) inhibitors. A vast number of current drugs on the market are inhibitors of enzymes whose action needs to be controlled in order to treat many conditions. This proposal will apply our new approaches to the design of enzyme inhibitors with superior therapeutic action. The benefits of this research reside in new treatments for a range of cardiovascular diseases (the 3rd largest cause of mortality in Australia) and provide a platform ....The design and synthesis of angiotensin converting enzyme-2 (ACE2) inhibitors. A vast number of current drugs on the market are inhibitors of enzymes whose action needs to be controlled in order to treat many conditions. This proposal will apply our new approaches to the design of enzyme inhibitors with superior therapeutic action. The benefits of this research reside in new treatments for a range of cardiovascular diseases (the 3rd largest cause of mortality in Australia) and provide a platform for new biotech companies to be formed in Australia.Read moreRead less
Differential Expression Proteomics: Identification and Quantitation of Peptides and Proteins by Fixed Charge Derivatization and Tandem Mass Spectrometry. The aim of this proposal is to develop novel strategies for the rapid, sensitive and selective identification and quantitation of proteins present in complex mixtures. Specifically, isotopically labeled fixed charge derivatives of peptides containing selected amino acids will be developed that direct the formation of product ions following tan ....Differential Expression Proteomics: Identification and Quantitation of Peptides and Proteins by Fixed Charge Derivatization and Tandem Mass Spectrometry. The aim of this proposal is to develop novel strategies for the rapid, sensitive and selective identification and quantitation of proteins present in complex mixtures. Specifically, isotopically labeled fixed charge derivatives of peptides containing selected amino acids will be developed that direct the formation of product ions following tandem mass spectrometry toward a single fragmentation channel. This approach will provide enhanced selectivity and sensitivity of up to 2 orders of magnitude over existing approaches, and will allow examination, at the protein level, of the complex cellular changes that occur following transformation of cells from a normal to a diseased state.Read moreRead less
Evolution, structure and function of key components in a molecular machine. The project will provide the basis for training of students and personnel in the previously recognized priority "Genomes-Phenomes", still the central theme of modern biology. In particular,
collaborations established with the Los Alamos National Laboratory in New Mexico will transfer to Australia expertise in the cutting edge discipline of small angle scattering for analysis of biologically important molecules. Such tr ....Evolution, structure and function of key components in a molecular machine. The project will provide the basis for training of students and personnel in the previously recognized priority "Genomes-Phenomes", still the central theme of modern biology. In particular,
collaborations established with the Los Alamos National Laboratory in New Mexico will transfer to Australia expertise in the cutting edge discipline of small angle scattering for analysis of biologically important molecules. Such training is essential for developing a future pool of skilled Australian scientists to staff and utilise the major national infrastructure developments represented by the Replacement Research Reactor and Australian Synchrotron, as outlined in the National Research Priority "Frontier Technologies".Read moreRead less
Investigating the subunit interactions of a molecular protein import machine. The project will provide fundamental knowledge of how sophisticated natural molecular machines interact with their substrates in plants and animals. It will also provide the basis for training of students and personnel in a range of structural biology technologies including several that are not commonly used by biologists, but make use of two major facilities that have been invested in by our government, namely the Aus ....Investigating the subunit interactions of a molecular protein import machine. The project will provide fundamental knowledge of how sophisticated natural molecular machines interact with their substrates in plants and animals. It will also provide the basis for training of students and personnel in a range of structural biology technologies including several that are not commonly used by biologists, but make use of two major facilities that have been invested in by our government, namely the Australian Synchrotron and the OPAL Research Reactor.Read moreRead less
Protein-mRNA interactions and their role in post-transcriptional regulation. The research outcomes will be of fundamental importance in the field of gene regulation, and as such will result in publications in high-profile international journals and continue to contribute to Australia's outstanding international reputation in biological research. Students and research associates that have the opportunity to work on this project will be trained in the use of state-of-the art technologies in bioche ....Protein-mRNA interactions and their role in post-transcriptional regulation. The research outcomes will be of fundamental importance in the field of gene regulation, and as such will result in publications in high-profile international journals and continue to contribute to Australia's outstanding international reputation in biological research. Students and research associates that have the opportunity to work on this project will be trained in the use of state-of-the art technologies in biochemistry, scientific rigour and presentation skills and thus contribute to the quality of our national workforce. Furthermore, applications that arise from this work will contribute to Australia's intellectual property and future development of biotechnological industry.Read moreRead less
Metalloproteomics: A new piece of the systems biology puzzle. Systems biology uses advanced analytical technology to study the complex chemistry of the living cell. Many cellular functions are the result of chemical reactions involving metalloproteins, which are notoriously difficult to study due to the weak bonds between metal and protein that is not normally amenable to traditional proteomic approaches. In partnership with the leading analytical manufacturer Agilent Technologies, this project ....Metalloproteomics: A new piece of the systems biology puzzle. Systems biology uses advanced analytical technology to study the complex chemistry of the living cell. Many cellular functions are the result of chemical reactions involving metalloproteins, which are notoriously difficult to study due to the weak bonds between metal and protein that is not normally amenable to traditional proteomic approaches. In partnership with the leading analytical manufacturer Agilent Technologies, this project aims to adapt and apply advanced mass spectrometry to the study of metalloproteins, developing new methods for studying hundreds of molecules in single experiments. Using the C. elegans model organism the project aims to showcase the importance of metals in biology and develop new solutions for the $2.9 billion proteomics industry.Read moreRead less
Molecular machines: regulation of the catalysis and rotation of the enzyme ATP synthase. This project aims to elucidate the regulation of the molecular machine ATP synthase. ATP synthase is an enzyme that performs a critical role in all cells - the synthesis of ATP, the universal biological energy currency. It is known that the enzyme operates via rotation of a central stalk which is driven by a hydrogen ion gradient across a membrane. Constructs of this molecule have been envisaged in the desig ....Molecular machines: regulation of the catalysis and rotation of the enzyme ATP synthase. This project aims to elucidate the regulation of the molecular machine ATP synthase. ATP synthase is an enzyme that performs a critical role in all cells - the synthesis of ATP, the universal biological energy currency. It is known that the enzyme operates via rotation of a central stalk which is driven by a hydrogen ion gradient across a membrane. Constructs of this molecule have been envisaged in the design of future biological nano-motors. Our work will provide an understanding of the regulation of this enzyme with potential application in the control of nano-motors.Read moreRead less
Multi-functional probes for global analysis of proteome stress in cells. This project aims to create a suite of multi-functional chemical probes to identify damaged proteins that undergo unfolding or specific modifications in cells under stress. These probes will not only generate fluorescence responses to reflect on protein quality control capacity but allow associated proteins and their networks to be identified in complex cellular environments, which is difficult to achieve by current methods ....Multi-functional probes for global analysis of proteome stress in cells. This project aims to create a suite of multi-functional chemical probes to identify damaged proteins that undergo unfolding or specific modifications in cells under stress. These probes will not only generate fluorescence responses to reflect on protein quality control capacity but allow associated proteins and their networks to be identified in complex cellular environments, which is difficult to achieve by current methods. The expected outcome is to deliver new methodology for a comprehensive understanding of the correlation between quality control machinery, stress responses and cell functions. This should provide significant benefits, including contributing to fundamental knowledge on the molecular causes of neurodegenerative diseases.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE0775708
Funder
Australian Research Council
Funding Amount
$289,680.00
Summary
X-ray Diffraction Microscope. The results of the research will substantially expand Australia's knowledge base in the area of diffraction, imaging and structural biology. It will build up our expertise in x-ray optics and synchrotron technology, and will open up a new approach to x-ray imaging and structure determination.
This will revolutionize our understanding of cellular and sub-cellular organisation with implications for the treatment of disease while the ability to determine structures ....X-ray Diffraction Microscope. The results of the research will substantially expand Australia's knowledge base in the area of diffraction, imaging and structural biology. It will build up our expertise in x-ray optics and synchrotron technology, and will open up a new approach to x-ray imaging and structure determination.
This will revolutionize our understanding of cellular and sub-cellular organisation with implications for the treatment of disease while the ability to determine structures of membrane proteins will open the door to fresh opportunities in rational drug design and biotechnology that will promote innovation in this industry, and the likely foundation of new start-up companies.Read moreRead less
Elucidating the determinants of cation import across the kingdoms of life. The metal ion manganese is essential to all forms of life. This project aims to investigate how this poorly abundant cation is selectively acquired from the chemical complexity of the environment for import into cells by using state-of-the-art biochemical and microbiological techniques. This project expects to define the fundamental basis for how bacterial, archaeal and eukaryotic plastid cation-selective importers can di ....Elucidating the determinants of cation import across the kingdoms of life. The metal ion manganese is essential to all forms of life. This project aims to investigate how this poorly abundant cation is selectively acquired from the chemical complexity of the environment for import into cells by using state-of-the-art biochemical and microbiological techniques. This project expects to define the fundamental basis for how bacterial, archaeal and eukaryotic plastid cation-selective importers can discriminate manganese from chemical similar cations to achieve selective uptake. The expected outcomes of this work will be an understanding of the fundamental basis for selective metal import in biological systems. This should provide benefits for industry through synthetic biological applications of this knowledge. Read moreRead less