How bacteria cause disease in the urinary tract. This project will investigate the virulence properties of uropathogenic Escherichia coli, the major causative agent of urinary tract infections (UTI) in humans. The results will help to understand how these bacterial pathogens cause disease and will impact strategies aimed at the prevention and treatment of chronic and recurrent UTI.
Activation of invasion in Toxoplasma. Host cell invasion is critical for the establishment and maintenance of infection by the single-celled parasite Toxoplasma gondii, the causative agent of Toxoplasmosis. This project will use the latest molecular techniques to understand how invasion is activated and will define a new set of drug targets to treat Toxoplasmosis and related diseases.
New models as tools for defining mechanisms of microbe survival in the urogenital tract. Bacteria that infect the human urogenital tract can cause serious disease and these infections represent a large cost to the health-care system world-wide. This study will focus on how bacteria survive in the human urogenital tract and this will impact on strategies aimed at preventing and treating these infections.
DNA end resection: from basic mechanisms to genome editing. The project aims to understand processes underlying genome editing, a bioengineering process that introduces specific mutations into genomic DNA. Homologous recombination and nonhomologous end-joining pathways play a crucial role in repairing broken DNA strands, which are a toxic form of DNA damage. The proteins that function in the repair process have been recently identified, but it remains unclear how they function on a mechanistic l ....DNA end resection: from basic mechanisms to genome editing. The project aims to understand processes underlying genome editing, a bioengineering process that introduces specific mutations into genomic DNA. Homologous recombination and nonhomologous end-joining pathways play a crucial role in repairing broken DNA strands, which are a toxic form of DNA damage. The proteins that function in the repair process have been recently identified, but it remains unclear how they function on a mechanistic level and how either of the two main pathways is selected. The project aims to define how the activity of a key control protein, Sae2 (Sporulation in the Absence of Spo Eleven), is regulated by posttranslational modifications, and how this activates homologous recombination. The project plans to first use Saccharomyces cerevisiae yeast as a model and then to extend research into the human system in an attempt to improve the efficiency of genome editing. Read moreRead less
Mechanisms of human immunodeficiency virus entry into cells. This project will develop an understanding of how human immunodeficiency virus (HIV) evolves in people to become better able to infect, and hence destroy, cells of the immune system. It is expected that new knowledge into how HIV alters the way it interacts with these cells will reveal insights for the design of vaccines, drugs and new diagnostic tests.
Immuno-epidemiological insights into the development of immunity to malaria and drug resistance. This project aims to better understand the maintenance and acquisition of immunity to malaria in high risk groups. It will also attempt to elucidate how immunity can interfere with the therapeutic efficacy of antimalarials, especially in the assessment of emerging drug resistance. The over-riding hypothesis is that differences in malaria transmission will lead to differential acquisition of immunity ....Immuno-epidemiological insights into the development of immunity to malaria and drug resistance. This project aims to better understand the maintenance and acquisition of immunity to malaria in high risk groups. It will also attempt to elucidate how immunity can interfere with the therapeutic efficacy of antimalarials, especially in the assessment of emerging drug resistance. The over-riding hypothesis is that differences in malaria transmission will lead to differential acquisition of immunity and efficacy of malaria interventions within and between populations. Understanding immunity to malaria is pivotal to develop new interventions, to understand the effectiveness of current malaria treatment and control programs to reduce the global burden of malarial disease.Read moreRead less
Transfer ribonucleic acid (tRNA) synthetases as drug targets in Plasmodium falciparum. Malaria is a major worldwide infectious disease. The disease kills around 2 million people every year, and current drugs are increasingly failing due to parasite drug resistance, creating an urgent demand for new drugs, that inhibit different targets. The Fellow will study a new class of parasite drug targets, the transfer ribonucleic acid (tRNA) synthetase enzymes to find novel inhibitors. Compounds blocking ....Transfer ribonucleic acid (tRNA) synthetases as drug targets in Plasmodium falciparum. Malaria is a major worldwide infectious disease. The disease kills around 2 million people every year, and current drugs are increasingly failing due to parasite drug resistance, creating an urgent demand for new drugs, that inhibit different targets. The Fellow will study a new class of parasite drug targets, the transfer ribonucleic acid (tRNA) synthetase enzymes to find novel inhibitors. Compounds blocking these enzymes may lead to new drugs to combat malaria.Read moreRead less
Beyond Spectral Detection: Engineering SUPER Dot Probes for High-Throughput Discovery. Molecules that are altered as a result of a pathological condition are generally present in very low abundance, and pose a “needle-in-a-haystack” problem. Current detection, quantification and localisation technologies use fluorescent probes that are limited by sensitivity and analysis time. This project will develop a new generation of nanophotonic luminescent probes (Strong Upconversion Photo-stable Encoded ....Beyond Spectral Detection: Engineering SUPER Dot Probes for High-Throughput Discovery. Molecules that are altered as a result of a pathological condition are generally present in very low abundance, and pose a “needle-in-a-haystack” problem. Current detection, quantification and localisation technologies use fluorescent probes that are limited by sensitivity and analysis time. This project will develop a new generation of nanophotonic luminescent probes (Strong Upconversion Photo-stable Encoded nano-Radiators (SUPER) Dots), based on purpose-engineered up-conversion nanocrystals that are ultra-bright and have low background interference, high specificity, speed, and large-scale multiplexing capacity. These probes will allow microscopy and flow cytometry to measure hitherto undetectable rare-event molecules and cells, opening new frontiers for the discovery of new biomarkers.Read moreRead less
Lipidomics of vision. Presbyopia and cataract are the major causes of visual impairment worldwide. Nevertheless, our understanding of lens ageing at both a cellular and molecular level is limited. This project will gain new insight into the effect of age on lens membrane lipids and their role in the development of presbyopia and cataract.
Improvement of anthracycline chemotherapy by enhancement of apoptotic responses and tumour targeted activation. Improved outcomes for anthracycline anticancer chemotherapy is of clear benefit to the nation. Tumour-localised treatment is expected to lead to improved responses, reduced side-effects and improved quality of life while rational selection of drug combinations is expected to enable treatment of tumours that were previously resistant to anthracyclines. With an aging population in Austra ....Improvement of anthracycline chemotherapy by enhancement of apoptotic responses and tumour targeted activation. Improved outcomes for anthracycline anticancer chemotherapy is of clear benefit to the nation. Tumour-localised treatment is expected to lead to improved responses, reduced side-effects and improved quality of life while rational selection of drug combinations is expected to enable treatment of tumours that were previously resistant to anthracyclines. With an aging population in Australia the incidence of cancer is predicted to rise dramatically - improved treatment outcomes and better use of chemotherapeutics will be of obvious national benefit. The development of new tumour-targeted agents is the subject of joint Intellectual Property between Australia and the USA, offering potential economic benefit. Read moreRead less