Linkage Infrastructure, Equipment And Facilities - Grant ID: LE0882295
Funder
Australian Research Council
Funding Amount
$225,000.00
Summary
X-ray crystallography resource for membrane proteins and large macromolecular complexes. Structural biology is the underpinning of biotechnology, biopharmaceuticals and rational therapeutic design. The most successful technique for determining the structures of proteins and large macromolecular complexes is x-ray crystallography. This proposal will set up a network of state of the art resources in the Sydney region to capitalise on expertise in these areas. The facilities will foster basic re ....X-ray crystallography resource for membrane proteins and large macromolecular complexes. Structural biology is the underpinning of biotechnology, biopharmaceuticals and rational therapeutic design. The most successful technique for determining the structures of proteins and large macromolecular complexes is x-ray crystallography. This proposal will set up a network of state of the art resources in the Sydney region to capitalise on expertise in these areas. The facilities will foster basic research and collaborations with industry, which will enhance Australia's profile and commercialisation of research. The facility will enhance the usage of the Australian synchrotron, producing flagship projects on the edge of technical possibilities.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE0214135
Funder
Australian Research Council
Funding Amount
$492,000.00
Summary
High performance protein crystallography. This proposal will provide state of the art high performance facilities for protein crystallography, bringing together the major structural biology groups in NSW and the ACT. A renewed focus on protein crystal structures will stimulate new interpretation and utilization of the vast amount of data that has come from genomics, especially the sequencing of the human genome. The proposed facility will generate new research collaborations between the partn ....High performance protein crystallography. This proposal will provide state of the art high performance facilities for protein crystallography, bringing together the major structural biology groups in NSW and the ACT. A renewed focus on protein crystal structures will stimulate new interpretation and utilization of the vast amount of data that has come from genomics, especially the sequencing of the human genome. The proposed facility will generate new research collaborations between the partner institutions which will result in advances in basic life sciences, biotechnology and biopharmaceuticals. The facility will complement regional initiatives in functional genomics, bioinformatics, proteomics and high-field NMR spectroscopy.Read moreRead less
New Proteins from the Mobile Genome: Structure-Led Discovery. The project will provide full descriptions of proteins with the capacity to become mobilised, as well as providing a source of completely novel genes with commercial potential. The proteins and enzymes discovered, and the metabolic processes with which they are identified, will have applications in a wide range of Australian industries: agriculture, forestry, pollution control and pharmaceutical design. This work therefore offers op ....New Proteins from the Mobile Genome: Structure-Led Discovery. The project will provide full descriptions of proteins with the capacity to become mobilised, as well as providing a source of completely novel genes with commercial potential. The proteins and enzymes discovered, and the metabolic processes with which they are identified, will have applications in a wide range of Australian industries: agriculture, forestry, pollution control and pharmaceutical design. This work therefore offers opportunities for many future directions in biotechnology, an area of growing strength in Australia. Read moreRead less
The role of the protease inhibitor Serpinb9 in antigen cross-presentation by dendritic cells. This project will provide fundamental new insights into antigen cross-presentation, a crucial facet of the immune system's response to viral infection or neoplastic cells. It will also provide a basis for future studies into mechanisms of immune tolerance and enhance our understanding of autoimmune disease.
The structure and function of dihydroorotase - an enzyme essential for pyrimidine biosynthesis. Malaria has recently re-emerged as one of the major life threatening diseases worldwide. With increasing travel and climate change, malaria is increasingly endangering Australians at home and abroad. Our work aims to provide the basis for the rational design of a new class of anti-malarial drugs by the systematic and thorough analysis of an essential enzyme in the malarial parasite.
Molecular Interactions in the Eubacterial Replisome: A Paradigm for Study of Dynamic Macromolecular Machines. Many pathogenic bacteria have developed resistance to antibiotics in common use, and new drugs are urgently required to kill them. Copying of their chromosomes before they divide into two new cells is essential for bacteria to live, so DNA synthesis is a good process to target for development of new antibiotics. This project will use state-of-the-art equipment available in several labora ....Molecular Interactions in the Eubacterial Replisome: A Paradigm for Study of Dynamic Macromolecular Machines. Many pathogenic bacteria have developed resistance to antibiotics in common use, and new drugs are urgently required to kill them. Copying of their chromosomes before they divide into two new cells is essential for bacteria to live, so DNA synthesis is a good process to target for development of new antibiotics. This project will use state-of-the-art equipment available in several laboratories in Australia and overseas to develop new understanding of how the molecular machine that copies DNA works. This k nowledge could lead to new drugs, and will give us new information about how cellular machines function.Read moreRead less
Fragment Based Screening for new Antibiotics by Protein X-Ray Crystallography. Due in part to rising levels of antibiotic resistance, the death toll from pathogenic bacteria is expected to skyrocket over the next 15 years. There is therefore a pressing need for new antibiotics to treat bacterial infection. This project will use a relatively new discovery tool called fragment based screening to discover a new generation of antibacterial agents. This tool will allow for the rapid economical discov ....Fragment Based Screening for new Antibiotics by Protein X-Ray Crystallography. Due in part to rising levels of antibiotic resistance, the death toll from pathogenic bacteria is expected to skyrocket over the next 15 years. There is therefore a pressing need for new antibiotics to treat bacterial infection. This project will use a relatively new discovery tool called fragment based screening to discover a new generation of antibacterial agents. This tool will allow for the rapid economical discovery of new drugs, and will complement other investments in Australian biotechnology infrastructure.Read moreRead less
Characterisation of a powerful molecular motor, the FtsK DNA translocase. The FtsK protein is a fast and powerful molecular motor, a pump that can, and does, move an entire bacterial chromosome. This project will uncover the detail of the mechanism used by this motor to convert the cell's chemical energy source Adenosine Triphosphate (ATP) into movement of DNA; revealing the molecular detail of a fast and powerful motor.
Functional Dissection of the Bacterial Replisome. This project aims to develop and use a suite of new single-molecule techniques to define how the bacterial replisome really works. The replisome is the machine that makes DNA in cells that are about to divide. Replisomes have many mechanistic challenges as they work to copy both strands of DNA at the same time. Many years of classic biochemical studies have worked out how many of these challenges are overcome. In recent years, the use of single-m ....Functional Dissection of the Bacterial Replisome. This project aims to develop and use a suite of new single-molecule techniques to define how the bacterial replisome really works. The replisome is the machine that makes DNA in cells that are about to divide. Replisomes have many mechanistic challenges as they work to copy both strands of DNA at the same time. Many years of classic biochemical studies have worked out how many of these challenges are overcome. In recent years, the use of single-molecule biophysical techniques has begun to challenge many aspects of the elegant textbook view of replisome function. This approach is expected to reveal how synthesis of the two DNA strands in different directions at the same time is coupled together and how timing mechanisms work.Read moreRead less
A functional dissection of the bacterial replisome. This project aims to study the replisome, the machine that duplicates DNA before cell division. Years of biochemical research has shown how its protein components work, but observation at the single-molecule level is needed to understand how they all work together. This project aims to combine novel single-molecule biophysical tools with state-of-the-art biochemistry to define how the bacterial replisome coordinates synthesis of the two DNA str ....A functional dissection of the bacterial replisome. This project aims to study the replisome, the machine that duplicates DNA before cell division. Years of biochemical research has shown how its protein components work, but observation at the single-molecule level is needed to understand how they all work together. This project aims to combine novel single-molecule biophysical tools with state-of-the-art biochemistry to define how the bacterial replisome coordinates synthesis of the two DNA strands and how it exchanges protein components on the fly. Expected outcomes of this project include improved understanding of a fundamental biological process, development of novel biophysical methodology, and training of the next generation of interdisciplinary scientists.Read moreRead less