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
New approaches to inhibition of activity of HIV integrase. This project aims to assist in the development of novel anti-HIV drugs that will benefit the 17000 Australians and more than 33 million people worldwide who are currently suffering with this terrible disease. The project will utilise state-of-the-art approaches in structure-based drug design to identify and synthesise compounds as leads for the development of anti-HIV drugs. Furthermore, the project will provide invaluable training for t ....New approaches to inhibition of activity of HIV integrase. This project aims to assist in the development of novel anti-HIV drugs that will benefit the 17000 Australians and more than 33 million people worldwide who are currently suffering with this terrible disease. The project will utilise state-of-the-art approaches in structure-based drug design to identify and synthesise compounds as leads for the development of anti-HIV drugs. Furthermore, the project will provide invaluable training for the researchers involved and enhance the relationship between the academic and commercial collaborators.Read moreRead less
Host cell targets of bacterial virulence effectors. The research described in this proposal will result in a better understanding of the cell biology of host-pathogen interactions. We are in a unique position to analyze the importance of protein/protein interactions between bacterial virulence determinants and host cell proteins using a range of cell biology techniques to address the fundamental, molecular basis of the host-pathogen interaction. In addition we will construct a new genetic tool ....Host cell targets of bacterial virulence effectors. The research described in this proposal will result in a better understanding of the cell biology of host-pathogen interactions. We are in a unique position to analyze the importance of protein/protein interactions between bacterial virulence determinants and host cell proteins using a range of cell biology techniques to address the fundamental, molecular basis of the host-pathogen interaction. In addition we will construct a new genetic tool to identify novel bacterial virulence determinants. We anticipate that a greater knowledge of the factors that contribute to the host-pathogen interaction will provide new insights into the subversion of host cell processes by bacterial pathogens of animals, plants and humans.
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New inhibitors of HIV based on cellular enzymes. Over 39 million people are infected with HIV worldwide. However, none of the most highly affected countries have yet reached the peak in AIDS-related illness and death, thus the global impact of HIV/AIDS will get significantly worse, before it gets better.
In Australia, HIV is again on the rise. Ironically, improved treatments that have extended life expectancy will cause the number of HIV infected Australians to rise for many years to come. ....New inhibitors of HIV based on cellular enzymes. Over 39 million people are infected with HIV worldwide. However, none of the most highly affected countries have yet reached the peak in AIDS-related illness and death, thus the global impact of HIV/AIDS will get significantly worse, before it gets better.
In Australia, HIV is again on the rise. Ironically, improved treatments that have extended life expectancy will cause the number of HIV infected Australians to rise for many years to come. Therefore many Australians will suffer from the combined impact of the AIDS illness itself, opportunistic infections, the side-effects of treatment and natural aging. We aim to develop new drugs to combat this disease to help people everywhere lead happier, healthier and more productive lives.Read moreRead less
Post-genomic investigation of the relict plastid and mitochondrion of malaria parasites. Malaria is a major global health problem. The malaria parasite has two substructures, a relict chloroplast and a mitochondrion, that are excellent targets for new and existing drugs. However, we do not know the key functions of these two compartments. The entire genetic blueprint (genome) is now available for the malaria parasite and I propose to determine exactly which parts of the genome service the rel ....Post-genomic investigation of the relict plastid and mitochondrion of malaria parasites. Malaria is a major global health problem. The malaria parasite has two substructures, a relict chloroplast and a mitochondrion, that are excellent targets for new and existing drugs. However, we do not know the key functions of these two compartments. The entire genetic blueprint (genome) is now available for the malaria parasite and I propose to determine exactly which parts of the genome service the relict chloroplast and mitochondria. This will sketch out a picture of their inner workings. Armed with this information we can take a rational approach to seeking an Achilles? Heel of malaria against which parasite-specific drugs can be developed.Read moreRead less
Transcriptional and epigenetic regulation of terminal lymphocyte differentiation and alterations of the same that lead to leukemia. In the developed world infection diseases are the number three killer behind heart disease and cancer, and huge financial effort is put into treatment and prevention. Despite this, results have often been disappointing. One cause of these poor outcomes is the lack of knowledge of how effective immune responses are generated. This project aims to better understand th ....Transcriptional and epigenetic regulation of terminal lymphocyte differentiation and alterations of the same that lead to leukemia. In the developed world infection diseases are the number three killer behind heart disease and cancer, and huge financial effort is put into treatment and prevention. Despite this, results have often been disappointing. One cause of these poor outcomes is the lack of knowledge of how effective immune responses are generated. This project aims to better understand the processes that control the generation of protective lymphocytes. It will deliver information that may enable a more targeted approach to vaccine-development and treatments of infections. As defective differentiation can also be a cause of leukemia it may also lead to targets of cancer treatment.Read moreRead less
Structure and function of novel transporters in alphaproteobacteria. First, detailed knowledge of a set of membrane transporters and the way their activity might be inhibited, will have implications for the treatment of human disease. Second, excellent outcomes are provided for the training of postgraduate students and research staff. This project entails cutting edge technology, and the transfer of technical capabilities not currently available in Australia. Third, our studies on non-pathogenic ....Structure and function of novel transporters in alphaproteobacteria. First, detailed knowledge of a set of membrane transporters and the way their activity might be inhibited, will have implications for the treatment of human disease. Second, excellent outcomes are provided for the training of postgraduate students and research staff. This project entails cutting edge technology, and the transfer of technical capabilities not currently available in Australia. Third, our studies on non-pathogenic species of alpha-proteobacteria provides for a timely advance in our knowledge of their biology: other species of alpha-proteobacteria were amongst the first organisms trialled for biological weapons by the USA and the former Soviet Union, and those pathogenic species are rated as Class 3 organisms.Read moreRead less
Molecular machines that drive microbial pathogens. We will provide a comprehensive understanding of molecular machines situated at the surface of bacteria. This ground-breaking research will provide excellent outcomes in the training of research students and staff: this project entails frontier technology, and the transfer of technological capabilities not currently available in Australia. Our study on a non-pathogenic species of bacteria is timely too for National security: related species of b ....Molecular machines that drive microbial pathogens. We will provide a comprehensive understanding of molecular machines situated at the surface of bacteria. This ground-breaking research will provide excellent outcomes in the training of research students and staff: this project entails frontier technology, and the transfer of technological capabilities not currently available in Australia. Our study on a non-pathogenic species of bacteria is timely too for National security: related species of bacteria were amongst the first organisms trialed as biological weapons, and the pathogenic species remain rated as Class 3 organisms by the Centers for Disease Control.Read moreRead less
Mitochondrial biogenesis: the evolution of molecular machines. Benefits from this research program fall into two discrete types. Firstly, excellent outcomes are provided for the training of postgraduate students and research staff. This project entails cutting edge technology, and the development of skills not common in Australia. Secondly, detailed knowledge will be gained of molecular machines and the way in which they may differ in human cells and in the cells of human cell parasites, with im ....Mitochondrial biogenesis: the evolution of molecular machines. Benefits from this research program fall into two discrete types. Firstly, excellent outcomes are provided for the training of postgraduate students and research staff. This project entails cutting edge technology, and the development of skills not common in Australia. Secondly, detailed knowledge will be gained of molecular machines and the way in which they may differ in human cells and in the cells of human cell parasites, with implications for the treatment of human disease.Read moreRead less
Reducible complexity in the molecular machines of humans and bacteria. Firstly, we will provide detailed knowledge of the surface membrane proteins of an important class of bacteria, the alpha-proteobacteria. Secondly, excellent outcomes are provided for the training of postgraduate students and research staff: this project entails frontier technology, and the transfer of technological capabilities not currently available in Australia. Thirdly, our studies on non-pathogenic species of alpha-prot ....Reducible complexity in the molecular machines of humans and bacteria. Firstly, we will provide detailed knowledge of the surface membrane proteins of an important class of bacteria, the alpha-proteobacteria. Secondly, excellent outcomes are provided for the training of postgraduate students and research staff: this project entails frontier technology, and the transfer of technological capabilities not currently available in Australia. Thirdly, our studies on non-pathogenic species of alpha-proteobacteria is timely for National security: species of alpha-proteobacteria were amongst the first organisms trialled as biological weapons by the USA and the former Soviet Union, and these pathogenic species remain rated as Class 3 organisms by the Centers for Disease Control. Read moreRead less