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Plasmodium Knowlesi As A Genetic Model For Plasmodium Vivax Drug Resistance
Funder
National Health and Medical Research Council
Funding Amount
$417,193.00
Summary
Two different Plasmodium parasites cause the majority of malaria worldwide. However, one type, P. vivax, is unable to be cultured in the laboratory and therefore has been poorly studied. Drug resistance has been observed but the underlying causes are poorly understood. We propose to use a closely related parasite, P. knowlesi, as a model to understand drug resistance mechanisms. This knowledge will be used to follow resistance in the field and direct policy of the most appropriate treatment.
Tailoring Targeted Therapy To DNA Repair-defective High-Grade Serous Ovarian Cancer
Funder
National Health and Medical Research Council
Funding Amount
$802,247.00
Summary
Ovarian cancer is a major cause of cancer death in women because current treatments are inadequate. Half of aggressive ovarian cancers have abnormalities in DNA repair and should be susceptible to new PARP inhibitor therapy, yet not all those respond. By developing a new model of studying human ovarian cancers in mice, we can discover markers to predict which ovarian cancers will respond best to these exciting new treatments.
Molecular Epidemiology Of Ovarian Cancer: The Australian Ovarian Cancer Study National Clinical Follow-Up Core
Funder
National Health and Medical Research Council
Funding Amount
$883,244.00
Summary
Ovarian cancer is the seventh most common cancer in Australian women and fifth most common cause of cancer death, with approximately 1200 new cases diagnosed and 750 deaths each year. There is an urgent need to better understand the molecular, epidemiological and genetic characteristics of epithelial ovarian cancer and how these influence response to treatment and clinical outcome. Ovarian cancer is a histologically and clinically diverse disease and the variability in clinical outcome in ovaria ....Ovarian cancer is the seventh most common cancer in Australian women and fifth most common cause of cancer death, with approximately 1200 new cases diagnosed and 750 deaths each year. There is an urgent need to better understand the molecular, epidemiological and genetic characteristics of epithelial ovarian cancer and how these influence response to treatment and clinical outcome. Ovarian cancer is a histologically and clinically diverse disease and the variability in clinical outcome in ovarian cancer patients suggests that reliable predictive factors would be of clinical value. However, it is clear that the collection of hundreds of annotated biospecimens is essential if the interaction of genes and environment in the genesis of this disease is to be understood or the molecular features of this disease dissected. Recognizing that this can only be achieved through large-scale collaboration, the Australian Ovarian Cancer Study (AOCS) was established in 2000 by scientists from the Peter MacCallum Cancer Centre, the Queensland Institute for Medical Research, Melbourne University and Westmead Institute for Cancer Research in collaboration with clinicians across Australia. AOCS has recruited 1105 patients to date and this Research Proposal aims to complete the collection of clinical data on all AOCS patients nationally, to validate the use of microarray gene expression profiles to predict clinical outcome and to find genetic variants that may determine clinical outcome in individual patients. The creation of AOCS has provided a unique oportunity to collect one of the finest ovarian cancer biological sample sets in the world. We believe that this internationally significant study will shed light on the basis of response of ovarian cancer to treatment and provide an ongoing resource for research into the causes of ovarian cancer, and studies on the response to treatment.Read moreRead less
Developing Species-specific, Structure-targeting Peptides As A Novel Class Of Antibiotics
Funder
National Health and Medical Research Council
Funding Amount
$607,967.00
Summary
Multidrug, antibiotic resistance is a serious global threat. It is a real possibility that in the absence of new antibiotics, common infections could soon become untreatable. This project will develop a novel class of antibiotics that target the core structures of essential bacterial proteins. The successful outcome of this work will also aid the development of specific peptide-based inhibitors for numerous additional diseases, including viral and fungal infections and cancer.
An Ace Up Their Sleeve: Characterisation Of A Novel Family Of Drug Efflux Systems Represented By The Acinetobacter AceI Exporter
Funder
National Health and Medical Research Council
Funding Amount
$400,286.00
Summary
Chlorhexidine is widely used as an antiseptic in products such as skin washes, soaps, mouthwashes, disinfectants and preservatives. We have recently discovered a novel bacterial protein which pumps chlorhexidine out of bacterial cells to make them resistant to this antiseptic agent. This proposal aims to understand this resistance mechanism and to find inhibitors which could be applied in clinical settings to augment the activity of chlorhexidine.
Fatty Acid Biosynthesis In The Malaria Chloroplast As A Drug Target
Funder
National Health and Medical Research Council
Funding Amount
$131,035.00
Summary
Malarial parasites contain a chloroplast similar to that of plants. We recently found genetic evidence suggesting the malaria chloroplast makes fats in the same way as plant chloroplasts. Additionally, we have found that drugs and herbicides that block plant chloroplast fat production stop growth of malaria cultures. Parasitologists had assumed that malaria was unable to make fats and would scavenge them from its human host so we have probably discovered a new metabolic pathway in these parasite ....Malarial parasites contain a chloroplast similar to that of plants. We recently found genetic evidence suggesting the malaria chloroplast makes fats in the same way as plant chloroplasts. Additionally, we have found that drugs and herbicides that block plant chloroplast fat production stop growth of malaria cultures. Parasitologists had assumed that malaria was unable to make fats and would scavenge them from its human host so we have probably discovered a new metabolic pathway in these parasites. We now propose to prove that the drugs work by blocking essential, chloroplast-based fat production in parasites. This could lead to novel treatment of malaria and related parasites.Read moreRead less
Functional Genomic Analysis Of Multidrug Efflux In The Emerging Pathogen Acinetobacter Baumannii
Funder
National Health and Medical Research Council
Funding Amount
$550,226.00
Summary
Infections due to antimicrobial resistant organisms are a major public health issue. Acinetobacter baumannii is a bacterium that is increasingly being identified as a significant cause of serious antibiotic resistant infections, especially in the intensive care unit setting. Molecular studies in Acinetobacter to identify and characterise drug resistance proteins that pump antibiotics out of the cell will help understand the resistance capabilities and potential of this bacterium.
The Fellowship would support Professor Bowtell, one of the world’s leading ovarian cancer researchers. His work focuses on clinical problems of chemotherapy resistance and the development of new therapeutic approaches. His studies are underpinned by the Australian Ovarian Cancer Study (AOCS), one of the world’s most sophisticated clinical cohort studies of ovarian cancer, with over 3000 Australian women enrolled.
ENU Mutagenesis To Identify Targets For Host-directed Therapy Against Malaria.
Funder
National Health and Medical Research Council
Funding Amount
$660,175.00
Summary
Malaria kills up to one million people annually, mainly children and pregnant women. The drugs that are used to treat malaria are becoming useless due to the malarial parasite developing resistance to these drugs. We are looking at a totally new way of developing drugs that target molecules in humans , depriving the parasites of crucial factors. By using this approach, the malaria parasite will be unable to develop resistance to these new drugs and millions of lives may be saved.