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
Mannosyl transfer processes in leishmania and mycobacteria. The human diseases leishmaniasis and tuberculosis are caused by infectious microorganisms. We will target pathways to the biosynthesis and degradation of parasite-specific mannose containing metabolites that play essential roles in the ability of these pathogens to cause disease. We will develop new ways to study these pathways, and will synthesize novel substrates and inhibitors that will allow the development of antituberculosis and a ....Mannosyl transfer processes in leishmania and mycobacteria. The human diseases leishmaniasis and tuberculosis are caused by infectious microorganisms. We will target pathways to the biosynthesis and degradation of parasite-specific mannose containing metabolites that play essential roles in the ability of these pathogens to cause disease. We will develop new ways to study these pathways, and will synthesize novel substrates and inhibitors that will allow the development of antituberculosis and antileishmanial drugs. This project will contribute to our national competitiveness in the newly emerging area of chemical biology.Read moreRead less
Mannose metabolism in pathogenic microorganisms. Current treatments for tuberculosis and leishmaniasis are failing due to chronic underinvestment by the private sector and public agencies over many decades. The causative agents, the microorganisms Leishmania spp and Mycobacterium tuberculosis, respectively, use sugar processing pathways that differ from humans, and thus represent targets for new drugs. We will study two related sugar-processing biochemical pathways in these organisms. We will de ....Mannose metabolism in pathogenic microorganisms. Current treatments for tuberculosis and leishmaniasis are failing due to chronic underinvestment by the private sector and public agencies over many decades. The causative agents, the microorganisms Leishmania spp and Mycobacterium tuberculosis, respectively, use sugar processing pathways that differ from humans, and thus represent targets for new drugs. We will study two related sugar-processing biochemical pathways in these organisms. We will develop new ways to measure enzyme activity using mass spectrometry, and new reagents to clone several biosynthetic enzymes. Our work will lay a foundation for new antibiotics to combat these insidious diseases, and will foster Australian expertise in chemical biology and innovative basic science.Read moreRead less
Total Synthesis of the Microsclerodermins: Anti-fungal Cyclic Peptides. Fungal infections are one of the major causes of morbidity and mortality in the increasing immunocompromised patient population, which includes AIDS, chemotherapy and organ transplant patients. The aim of this project is to discover new anti-fungal treatments for drug-resistant pathogenic fungal infections, based on the microsclerodermin family of natural products. The small quantity of microsclerodermin isolated from the na ....Total Synthesis of the Microsclerodermins: Anti-fungal Cyclic Peptides. Fungal infections are one of the major causes of morbidity and mortality in the increasing immunocompromised patient population, which includes AIDS, chemotherapy and organ transplant patients. The aim of this project is to discover new anti-fungal treatments for drug-resistant pathogenic fungal infections, based on the microsclerodermin family of natural products. The small quantity of microsclerodermin isolated from the natural environment hampers the development of anti-fungal agents from this natural product. Innovative synthetic methods will be developed to prepare large quantities of microsclerodermins and related compounds for biological testing, thereby furthering the development of this promising class of anti-fungal drugs.Read moreRead less
Inhibitors of enzymes in the lysine biosynthetic pathway. Recent reports of increasing bacterial resistance to antibiotics highlight the need for continual development of new antibacterial agents. Inhibitors of the biosynthesis of the amino acid lysine - an essential component of bacterial proteins and cell wall - may provide a novel class of antibiotics. This project describes investigations of the mechanism of the first two enzymes in the lysine biosynthetic pathway and the design and synthesi ....Inhibitors of enzymes in the lysine biosynthetic pathway. Recent reports of increasing bacterial resistance to antibiotics highlight the need for continual development of new antibacterial agents. Inhibitors of the biosynthesis of the amino acid lysine - an essential component of bacterial proteins and cell wall - may provide a novel class of antibiotics. This project describes investigations of the mechanism of the first two enzymes in the lysine biosynthetic pathway and the design and synthesis of inhibitors of these enzymes.Read moreRead less
Design and Development of HIV-1 Integrase Inhibitors Based on a Natural Product Lead. HIV/AIDS is a significant health problem with over 40 million people infected with HIV worldwide. Resistance to current drugs is rising rapidly and new therapeutics are urgently needed. This project will bring together local expertise in organic synthesis and virology in order to develop new and better treatments for HIV/AIDS. Ultimately, Australians with HIV may benefit directly from anti-HIV compounds produce ....Design and Development of HIV-1 Integrase Inhibitors Based on a Natural Product Lead. HIV/AIDS is a significant health problem with over 40 million people infected with HIV worldwide. Resistance to current drugs is rising rapidly and new therapeutics are urgently needed. This project will bring together local expertise in organic synthesis and virology in order to develop new and better treatments for HIV/AIDS. Ultimately, Australians with HIV may benefit directly from anti-HIV compounds produced and may also benefit from advances in our understanding of this elusive virus resulting from the project.Read moreRead less
Raman and synchrotron spectroscopy of nano-scale drug interactions and molecular processes in single living cells. The need for potent low-cost drugs is ever increasing, yet effective ways to screen for new drugs remain elusive. A spectroscopic approach to screening drugs in living cells would seem a logical alternative to chemically based and morphological methods that are the status quo. In this context we are developing methodology to analyse molecular target sites in single living cells for ....Raman and synchrotron spectroscopy of nano-scale drug interactions and molecular processes in single living cells. The need for potent low-cost drugs is ever increasing, yet effective ways to screen for new drugs remain elusive. A spectroscopic approach to screening drugs in living cells would seem a logical alternative to chemically based and morphological methods that are the status quo. In this context we are developing methodology to analyse molecular target sites in single living cells for two of the most devastating diseases to afflict human kind, namely malaria and cancer. New ways of rapidly screening drugs in living cells prior to clinical trials will save an enormous amount of time, money and ultimately lives.Read moreRead less
An Investigation of Novel Sialylmimetics as Inhibitors of Rotavirus. Rotavirus causes severe gastroenteritis in infants worldwide. Over 125 million cases of diarrhoea and 800,000 deaths annually are attributed to rotavirus. The process that enables this debilitating and sometimes fatal disease to infect cells is poorly understood. This project aims to produce a range of unique chemical entities that will provide information about the way rotavirus infects cells. The chemical compounds produc ....An Investigation of Novel Sialylmimetics as Inhibitors of Rotavirus. Rotavirus causes severe gastroenteritis in infants worldwide. Over 125 million cases of diarrhoea and 800,000 deaths annually are attributed to rotavirus. The process that enables this debilitating and sometimes fatal disease to infect cells is poorly understood. This project aims to produce a range of unique chemical entities that will provide information about the way rotavirus infects cells. The chemical compounds produced in this study will be evaluated for their ability to prevent rotavirus from infecting cells. It is expected that this project will provide compounds that may ultimately be used as drugs for the treatment of rotavirus.Read moreRead less
An Investigation of Novel Sialylmimetics as Inhibitors of Rotavirus. Rotavirus causes severe gastroenteritis in infants worldwide. Over 125 million cases of diarrhoea and 800,000 deaths annually are attributed to rotavirus, primarily in developing countries. The process that enables this debilitating and sometimes fatal disease to infect cells is poorly understood. This project aims to produce a range of unique chemical entities that will provide information about the way rotavirus infects cel ....An Investigation of Novel Sialylmimetics as Inhibitors of Rotavirus. Rotavirus causes severe gastroenteritis in infants worldwide. Over 125 million cases of diarrhoea and 800,000 deaths annually are attributed to rotavirus, primarily in developing countries. The process that enables this debilitating and sometimes fatal disease to infect cells is poorly understood. This project aims to produce a range of unique chemical entities that will provide information about the way rotavirus infects cells. The chemical compounds produced will be assayed for their ability to prevent rotavirus from infecting cells. It is expected that this project will provide compounds that may ultimately be used as drugs for the treatment of rotavirus.Read moreRead less
Structure-based discovery of anti-rotaviral agents. Rotavirus causes, particularly in children under 5 years of age, significant loss of life worldwide. Over 600,000 children under 5 years of age per annum die as a result of rotavirus infection. Australia records over 10,000 hospitalisations per annum due to rotavirus infection. This project aims, using structure-based drug design techniques, to develop inhibitors of a rotavirus protein that is essential in its lifecycle. These inhibitors may ....Structure-based discovery of anti-rotaviral agents. Rotavirus causes, particularly in children under 5 years of age, significant loss of life worldwide. Over 600,000 children under 5 years of age per annum die as a result of rotavirus infection. Australia records over 10,000 hospitalisations per annum due to rotavirus infection. This project aims, using structure-based drug design techniques, to develop inhibitors of a rotavirus protein that is essential in its lifecycle. These inhibitors may lead to the development of useful drugs to treat rotavirus infection and may reduce significant loss of life caused by this deadly virus.Read moreRead less