Allosteric regulation, molecular structure and function of transglutaminase 2. With Australia's ageing population, we can expect to see increasing prevalence of pathologies such as cancer, Alzheimer's disease, and cataracts. The ubiquitous enzyme transglutaminase 2 (TG2) has been implicated in all of these age-related diseases, as well as in chronic disorders such as coeliac disease and diabetes, and may contribute in a positive way to wound healing. Understanding how TG2 is activated and inac ....Allosteric regulation, molecular structure and function of transglutaminase 2. With Australia's ageing population, we can expect to see increasing prevalence of pathologies such as cancer, Alzheimer's disease, and cataracts. The ubiquitous enzyme transglutaminase 2 (TG2) has been implicated in all of these age-related diseases, as well as in chronic disorders such as coeliac disease and diabetes, and may contribute in a positive way to wound healing. Understanding how TG2 is activated and inactivated, and how it selects its targets, will be a critical addition to current knowledge of this enzyme, and will be an essential prerequisite for the development of TG2-targetted drugs and other TG2-related therapies.Read moreRead less
Stuctural analysis of RNA polymerase elongation complexes. RNA polymerase (RNAP) is an essential enzyme in all living cells. Its role is to convert the genetic information stored in genes into a message that can be converted into protein. Many additional factors are required to ensure that this enzyme functions correctly in the cell. The aim of this project is to obtain structural information on a bacterial RNAP complexed with an essential transcription factor called NusA. Using this information ....Stuctural analysis of RNA polymerase elongation complexes. RNA polymerase (RNAP) is an essential enzyme in all living cells. Its role is to convert the genetic information stored in genes into a message that can be converted into protein. Many additional factors are required to ensure that this enzyme functions correctly in the cell. The aim of this project is to obtain structural information on a bacterial RNAP complexed with an essential transcription factor called NusA. Using this information, plus data already obtained on the structure of this enzyme complexed with another essential factor called sigma, we will design small molecules to inhibit the interaction of these essential factors with polymerase. These molecules will serve as leads for the development of new antibiotics.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE100100177
Funder
Australian Research Council
Funding Amount
$300,000.00
Summary
Advanced electron paramagnetic resonance (EPR) facilities for chemical, biological and materials sciences. New instrumentation to advance national research in hydrogen fuel generation from renewable sources, new generation photo-voltaic technologies, novel polymer and other chemical materials and advanced computing systems will be provided by this project. A new high sensitivity electron paramagnetic resonance facility, located at the Australian National University, will serve researchers in the ....Advanced electron paramagnetic resonance (EPR) facilities for chemical, biological and materials sciences. New instrumentation to advance national research in hydrogen fuel generation from renewable sources, new generation photo-voltaic technologies, novel polymer and other chemical materials and advanced computing systems will be provided by this project. A new high sensitivity electron paramagnetic resonance facility, located at the Australian National University, will serve researchers in the ACT region devoted to the broad range of activities summarised above. A particular focus involves novel, biologically inspired energy systems and high efficiency solar cell technology.Read moreRead less
Guarding and evolving the genome: interactions between DNA-repair enzymes and damaged DNA. The application of structural biology techniques to the area of DNA repair allows us to understand the full implications linking genes and proteins to the molecular mechanisms of diseases such as cancer and hereditory conditions. Studies in this highly internationally competitive area are already established in the Bond laboratory, which has recently relocated to Australia. The use of forward-thinking stru ....Guarding and evolving the genome: interactions between DNA-repair enzymes and damaged DNA. The application of structural biology techniques to the area of DNA repair allows us to understand the full implications linking genes and proteins to the molecular mechanisms of diseases such as cancer and hereditory conditions. Studies in this highly internationally competitive area are already established in the Bond laboratory, which has recently relocated to Australia. The use of forward-thinking structural biology approaches to solve difficult technical problems will foster collaborations within Australia and with leading laboratories abroad, providing excellent up-to-date research training for students and postdoctoral researchers.
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Linkage Infrastructure, Equipment And Facilities - Grant ID: LE110100171
Funder
Australian Research Council
Funding Amount
$200,000.00
Summary
Shared resource for protein discovery. This facility will enable the production and characterisation of proteins from all kingdoms of life that have diverse roles in fundamental biology and disease. A detailed understanding of how these proteins behave and function will be used to generate therapeutics and develop novel applications for these proteins in medicine and industry.
Mechanistic Studies of Dimethylsulfide Dehydrogenase: A Novel Bacterial Molybdoenzyme. The aim of this proposal is to use electrochemical, spectroscopic and molecular biological techniques to understand the mechanism of action of the enzyme dimethylsulfide dehydrogenase. This enzyme is representative of an major group of molybdenum-containing enzymes that have importance in microbial biotransformations. The project will provide fundamental information about a multi-redox centre protein that has ....Mechanistic Studies of Dimethylsulfide Dehydrogenase: A Novel Bacterial Molybdoenzyme. The aim of this proposal is to use electrochemical, spectroscopic and molecular biological techniques to understand the mechanism of action of the enzyme dimethylsulfide dehydrogenase. This enzyme is representative of an major group of molybdenum-containing enzymes that have importance in microbial biotransformations. The project will provide fundamental information about a multi-redox centre protein that has potential application in biosensors and biocatalysis.Read moreRead less
Structural studies of catalysis and electron transfer by copper proteins. We propose to determine the crystal structures of five copper-containing proteins. Three are amine oxidases, enzymes that protect a wide range of organisms against toxic cell products (amines). Novel chemical modifications and crystallographic techniques will be used to test hypotheses for the enzyme mechanism. The results will provide a basis for the future manipulation of the enzymes' activities. Our other targets, s ....Structural studies of catalysis and electron transfer by copper proteins. We propose to determine the crystal structures of five copper-containing proteins. Three are amine oxidases, enzymes that protect a wide range of organisms against toxic cell products (amines). Novel chemical modifications and crystallographic techniques will be used to test hypotheses for the enzyme mechanism. The results will provide a basis for the future manipulation of the enzymes' activities. Our other targets, sulfocyanin and auracyanin-A, perform essential electron-transfer functions in an archaeon and a photosynthetic bacterium, respectively. The determination of their molecular structures will answer exciting questions about electron transfer in primitive organisms, and about the evolution of copper proteins as biological electron-transfer agents.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE0344441
Funder
Australian Research Council
Funding Amount
$390,000.00
Summary
New Generation Metalloenzyme Magnetic Circular Dichroism Spectrometer Systems. Funding is sought to enhance the existing collaborations between UQ, ANU, Sydney and other universities in the study of metal-centred molecules of biological interest through the construction of advanced magnetic circular dichroism (MCD) spectrometers. These facilities will be the best instruments of their kind, and will enable researchers at Australian institutions to enhance the quality of their research and remain ....New Generation Metalloenzyme Magnetic Circular Dichroism Spectrometer Systems. Funding is sought to enhance the existing collaborations between UQ, ANU, Sydney and other universities in the study of metal-centred molecules of biological interest through the construction of advanced magnetic circular dichroism (MCD) spectrometers. These facilities will be the best instruments of their kind, and will enable researchers at Australian institutions to enhance the quality of their research and remain internationally competitive through the application of modern MCD spectroscopic techniques to the study of metal-centred biomolecules. These facilities will drive a number of programs in the area of metalloenzyme and photosystem II research.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE0560685
Funder
Australian Research Council
Funding Amount
$451,000.00
Summary
Scanning Probe Microscopy for Bioelectrochemistry. New methods to study the fundamental properties of biological samples, in particular proteins, are continuing to advance and impact on society. We will establish a leading edge facility for high-resolution imaging of biomolecules with redox functions. This will enable the continued development of new enzyme based diagnostic tests by understanding the dynamic nature of coupled electron and molecular interactions with redox enzymes in solution. Th ....Scanning Probe Microscopy for Bioelectrochemistry. New methods to study the fundamental properties of biological samples, in particular proteins, are continuing to advance and impact on society. We will establish a leading edge facility for high-resolution imaging of biomolecules with redox functions. This will enable the continued development of new enzyme based diagnostic tests by understanding the dynamic nature of coupled electron and molecular interactions with redox enzymes in solution. The bioelectrochemical imaging facility will be unique in Australia and establish an important cross-disciplinary approach within the international community.Read moreRead less
Chemical synthesis of cancer-associated glycoproteins. Glycosylation of proteins is an extremely common event which plays an important role in a variety of biological processes. Aberrant glycosylation and over-production of glycoproteins is associated with numerous cancer types (including breast, prostate, ovarian and small lung) and are recognised as promising agents for disease diagnosis and vaccine development. A range of cancer-associated glycoproteins will be synthesised in this research p ....Chemical synthesis of cancer-associated glycoproteins. Glycosylation of proteins is an extremely common event which plays an important role in a variety of biological processes. Aberrant glycosylation and over-production of glycoproteins is associated with numerous cancer types (including breast, prostate, ovarian and small lung) and are recognised as promising agents for disease diagnosis and vaccine development. A range of cancer-associated glycoproteins will be synthesised in this research program using a number of novel chemical technologies. These glycoproteins will be used to develop cancer vaccines and diagnostics. Cancer is a severe burden on the Australian community and on the economy, therefore this research will be of significant benefit to Australia.Read moreRead less