Preventing The Evolution Of Transmissible Nitroimidazole Resistance In Mycobacterium Tuberculosis
Funder
National Health and Medical Research Council
Funding Amount
$664,463.00
Summary
Tuberculosis kills more people than any other infectious disease. Unfortunately, the drugs available to us to treat TB are losing their efficacy due to the evolution of drug resistance. A new class of drugs, nitroimidazoles, has been developed, but there is a risk that the bacterium that causes TB will develop resistance to these compounds too. We will identify resistance mutations before they occur in the wild, to help identify them and find new compounds for which resistance cannot develop.
DsbA Foldases From Multidrug Resistant Pathogens As Targets For New Antimicrobials
Funder
National Health and Medical Research Council
Funding Amount
$743,401.00
Summary
Bacteria that cause common human infections, such as cystitis and diarrhoea, are now resistant to many antibiotics. If no action is taken, by 2050 antibiotic resistant infections will kill more people each year than cancer. This project aims to address this global public health crisis by characterising promising new bacterial targets and inhibitors designed to disarm multidrug resistant pathogens. Longer term this work could provide new infection therapies that are urgently needed.
Structure, Assembly, And Inhibition Of The Human Telomerase Enzyme Complex
Funder
National Health and Medical Research Council
Funding Amount
$645,359.00
Summary
In contrast to the limited growth of normal human cells, cancer cells proliferate out of control and without limit. At least 85% of all human cancers rely on the enzyme TELOMERASE to sustain their unlimited proliferation. Telomerase is absent in most normal tissues and therefore represents a potentially effective and specific target for future cancer therapy. We aim to determine the precise 3-dimensional shape of human telomerase to provide a template for rational anti-telomerase drug design.
Functional evolution and therapeutic potential of snake venom coagulotoxins. This project aims to identify and understand the factors that influence the useful function of key residues (parts of larger compounds) in Australian snake venom coagulotoxins, which alter blood-clotting ability. In recent years, snake venom compounds have been demonstrated as useful models from which to synthesise therapeutic drugs to improve health and well-being. This project will test these important toxins on model ....Functional evolution and therapeutic potential of snake venom coagulotoxins. This project aims to identify and understand the factors that influence the useful function of key residues (parts of larger compounds) in Australian snake venom coagulotoxins, which alter blood-clotting ability. In recent years, snake venom compounds have been demonstrated as useful models from which to synthesise therapeutic drugs to improve health and well-being. This project will test these important toxins on model systems that represent natural prey items in order to determine the molecular and functional evolution of blood-clot forming enzymes. Expected outcomes include substantial contributions to the body of evolutionary biology knowledge, as well as narrowing the search for the ultimate drug candidates.Read moreRead less
Modulation of cellular metabolism by protein and peptide peroxides. Oxidation of peptides and proteins by a wide range of reactive radicals and other oxidants, in the presence of oxygen, generates protein peroxides. These species are now recognised to be key intermediates in both the deterioration of foods (e.g. development of rancidity and off-flavours, changes in colour and texture) and a number of human diseases, including cancer, heart disease and ageing. How these peroxides cause biological ....Modulation of cellular metabolism by protein and peptide peroxides. Oxidation of peptides and proteins by a wide range of reactive radicals and other oxidants, in the presence of oxygen, generates protein peroxides. These species are now recognised to be key intermediates in both the deterioration of foods (e.g. development of rancidity and off-flavours, changes in colour and texture) and a number of human diseases, including cancer, heart disease and ageing. How these peroxides cause biological perturbations is poorly understood. The proposed studies will provide valuable information as to how these peroxides affect cellular metabolism and provide key leads as to strategies which may prevent such damage.Read moreRead less
Mechanistic studies on the oxidation of amino acids, peptides and proteins and its biological consequences. Exposure of amino acids and proteins to radicals, oxidants, UV light, and metal ions results in oxidation, with consequent alteration to protein structure and function. It has been shown that these reactions occur during food spoilage, exposure of plants to excess UV light, and in a number of human diseases (e.g. heart disease and cancer). Despite evidence for a key role for protein oxidat ....Mechanistic studies on the oxidation of amino acids, peptides and proteins and its biological consequences. Exposure of amino acids and proteins to radicals, oxidants, UV light, and metal ions results in oxidation, with consequent alteration to protein structure and function. It has been shown that these reactions occur during food spoilage, exposure of plants to excess UV light, and in a number of human diseases (e.g. heart disease and cancer). Despite evidence for a key role for protein oxidation in these events, the fundamental chemistry and biochemistry of protein oxidation is incompletely understood. This is addressed in this project. Knowledge of the mechanisms of these reactions is a vital pre-requisite to the rational design of preventative strategies that might enhance food quality, minimise UV damage and enhance human health.Read moreRead less
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
Australian Laureate Fellowships - Grant ID: FL140100027
Funder
Australian Research Council
Funding Amount
$2,898,150.00
Summary
Under the hood: single-molecule studies of multi-protein machines. Under the hood: single-molecule studies of multi-protein machines. Living cells are filled with complex protein machines that are responsible for the molecular processes supporting life. This project is aimed towards the development of physical tools that enable the study of these protein complexes at the level of single molecules. This project aims to study the protein machinery responsible for DNA replication, the process of du ....Under the hood: single-molecule studies of multi-protein machines. Under the hood: single-molecule studies of multi-protein machines. Living cells are filled with complex protein machines that are responsible for the molecular processes supporting life. This project is aimed towards the development of physical tools that enable the study of these protein complexes at the level of single molecules. This project aims to study the protein machinery responsible for DNA replication, the process of duplicating genomic information before cell division. By making real-time single-molecule movies of the replication process, this project aims to unravel the molecular mechanisms of this important process and provide the knowledge required to understand disease mechanisms and catalyse drug development.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE0561013
Funder
Australian Research Council
Funding Amount
$220,000.00
Summary
X-ray diffraction System for Protein Crystallography and Structural Biology. Knowledge of protein structures enables researchers to explain cellular function at a molecular level. In particular, it provides essential information to understand the mechanism of diseases, such as cancer or AIDS, and it ultimately leads to the design of better drugs.
An in-house X-ray protein crystallography facility will allow us to determine the structures of key proteins effectively and competitively, opening up ....X-ray diffraction System for Protein Crystallography and Structural Biology. Knowledge of protein structures enables researchers to explain cellular function at a molecular level. In particular, it provides essential information to understand the mechanism of diseases, such as cancer or AIDS, and it ultimately leads to the design of better drugs.
An in-house X-ray protein crystallography facility will allow us to determine the structures of key proteins effectively and competitively, opening up extensive possibilities for multi-disciplinary ground-breaking research.
The University research portfolio has evolved to embrace the revolution in structural biology with numerous projects and collaborations focusing on proteins involved in bacterial infections, degenerative disorders and biotechnological applications.Read moreRead less
Australian Laureate Fellowships - Grant ID: FL0992138
Funder
Australian Research Council
Funding Amount
$3,100,000.00
Summary
Towards antibacterials without resistance. Innovative automation technologies will be used to create and investigate a revolutionary new approach to disable pathogenic superbugs, bacteria resistant to multiple antibiotics. The chemicals created and proteins evaluated in this research program will advance fundamental knowledge about the molecular weapons that bacteria produce to cause disease; deliver social and economic benefits to Australia through the development of potential new antibacterial ....Towards antibacterials without resistance. Innovative automation technologies will be used to create and investigate a revolutionary new approach to disable pathogenic superbugs, bacteria resistant to multiple antibiotics. The chemicals created and proteins evaluated in this research program will advance fundamental knowledge about the molecular weapons that bacteria produce to cause disease; deliver social and economic benefits to Australia through the development of potential new antibacterial treatments; contribute to Australia's continued international leading role in drug discovery research; enhance international links and attract industry investment in Australia; and provide a stimulating research training environment to inspire and motivate the next generation of scientists.Read moreRead less