Griseofulvin, A Novel Host-directed Antimalarial Drug
Funder
National Health and Medical Research Council
Funding Amount
$461,551.00
Summary
This grant is for a Phase II clinical trial to test an FDA & TGA approved drug for a new use as an antimalarial drug. The parasite uses an enzyme from the human RBC to help it replicate & early trials show this drug appears to disrupt the life cycle of the parasite. This Phase II clinical trial will test the drug on human subjects, & if successful, the drug will be a new and novel way in which to treat and prevent malarial infections in humans.
Targeting An Ion Pump In The Malaria Parasite With Multiple Compound Classes
Funder
National Health and Medical Research Council
Funding Amount
$384,686.00
Summary
Large-scale antimalarial drug screening projects have identified three different classes of compound that kill the malaria parasite at extremely low doses and which hold real promise as next-generation antimalarials. Genetic evidence, as well as preliminary data from our own lab, has led us to the hypothesis that all three compound classes exert their antimalarial effect by blocking a molecular ion pump on the parasite surface. The aim of this study is to test this.
Identifying potential barriers to transplanting modified forms of the CO2-fixing enzyme, Rubisco, into plants. Improving the ability of crops to use water, light and fertiliser more efficiently would have economic benefits and ease the environmental impacts associated with agricultural practices. It is thought that such improvements can be made by enhancing the efficiency of the photosynthetic protein, Rubisco, which fixes most of the CO2 in the biosphere. The research proposed here uses unique ....Identifying potential barriers to transplanting modified forms of the CO2-fixing enzyme, Rubisco, into plants. Improving the ability of crops to use water, light and fertiliser more efficiently would have economic benefits and ease the environmental impacts associated with agricultural practices. It is thought that such improvements can be made by enhancing the efficiency of the photosynthetic protein, Rubisco, which fixes most of the CO2 in the biosphere. The research proposed here uses unique Rubisco transplantation capabilities that I have developed to improve our fundamental understanding of how Rubisco is processed and its activity regulated in plants. This will pave the way for our ongoing efforts to engineer and transplant more efficient Rubisco into crops.Read moreRead less
The Role Of Duffy And PF4 In The Platelet Killing Of Malaria Parasites.
Funder
National Health and Medical Research Council
Funding Amount
$350,045.00
Summary
Platelets in the blood can kill the Plasmodium parasite, which lives inside red blood cells and causes malaria. Platelets bind parasite-infected red cells and release a molecule that is toxic to the parasite. This project will study why a red cell molecule called Duffy is also needed for this function of platelets. Most Africans carry a gene for Duffy that stops its expression in red cells, and may therefore be more susceptible to malaria because their platelets cannot kill the malaria parasite.
ADAM Metalloprotease Inhibition For Treatment Of Colorectal Cancer
Funder
National Health and Medical Research Council
Funding Amount
$770,925.00
Summary
Colorectal cancer (CRC) causes over 4000 deaths/year, typically from developing drug resistance and spreading to other organs (metastasis). These processes involve tumour cells called cancer stem cells (CSCs), which rely on specific cell surface proteins for survival and function. We are developing antibodies against one of these type of proteins, to test in mouse models of CRC. These already show promise in targeting CSCs and inhibiting drug-resistance and metastasis in mice.
Can efficient algal variants of the photosynthetic CO2-fixing enzyme, Rubisco, be folded and assembled in functional forms in higher-plant plastids? We have shown that it is possible to alter the photosynthetic phenotype of a plant predictably and profoundly by engineering the plastid genome to replace the plant's CO2-fixing enzyme, Rubisco, with a bacterial homolog. Thus it may be possible to replace the plant enzyme with more efficient algal Rubiscos that would allow plants to grow with less l ....Can efficient algal variants of the photosynthetic CO2-fixing enzyme, Rubisco, be folded and assembled in functional forms in higher-plant plastids? We have shown that it is possible to alter the photosynthetic phenotype of a plant predictably and profoundly by engineering the plastid genome to replace the plant's CO2-fixing enzyme, Rubisco, with a bacterial homolog. Thus it may be possible to replace the plant enzyme with more efficient algal Rubiscos that would allow plants to grow with less light, less water or less fertiliser. Before such desirable changes to the plant phenotype can be realised, some complex issues of modification, folding and assembly of Rubisco subunits need to be resolved. This proposal addresses them.Read moreRead less
Mechanisms Of Glucocorticoid Resistance In Acute Lymphoblastic Leukaemia
Funder
National Health and Medical Research Council
Funding Amount
$547,970.00
Summary
Glucocorticoids are extremely active drugs used in the treatment of childhood acute lymphoblastic leukaemia (ALL), yet a proportion of patients respond poorly to therapy and exhibit resistance at relapse. Clinically relevant mechanisms of glucocorticoid resistance are poorly understood, principally due to lack of appropriate experimental models. This project will reveal novel mechanisms of drug resistance in childhood leukaemia and lead to novel therapeutic strategies to improve outcome.
Role of alanine aminotransferase in improved nitrogen use efficiency (NUE) in cereals. The use of nitrogen-based fertilisers by crop plants is poor where efficiencies (nitrogen taken up to that applied) is often less than 40%. Nitrogen not used is often lost to the environment through leaching and or volatilisation. Improving nitrogen use efficiency (NUE) in agriculture will decrease overall nitrogen fertiliser use and minimise its environmental footprint. This project will characterise a nov ....Role of alanine aminotransferase in improved nitrogen use efficiency (NUE) in cereals. The use of nitrogen-based fertilisers by crop plants is poor where efficiencies (nitrogen taken up to that applied) is often less than 40%. Nitrogen not used is often lost to the environment through leaching and or volatilisation. Improving nitrogen use efficiency (NUE) in agriculture will decrease overall nitrogen fertiliser use and minimise its environmental footprint. This project will characterise a novel NUE technology that when transferred to plants significantly improves NUE. We will define the phenotype at the molecular, biochemical and physiological levels to maximise its adoption to other agricultural crops such as wheat, barley and maize.Read moreRead less
Evolution in microsatellite DNA: testing models of mutation in an Australian marsupial. We aim to compare mutational events between microsatellite loci that vary in their exposure to recombination. We are able to do this because of a remarkable finding that Australian brushtail possums have multiple occurrences of a single microsatellite repeat element within the Y-chromosome and among autosomal loci. We will compare variation between the Y-linked and non Y-linked loci within and among individu ....Evolution in microsatellite DNA: testing models of mutation in an Australian marsupial. We aim to compare mutational events between microsatellite loci that vary in their exposure to recombination. We are able to do this because of a remarkable finding that Australian brushtail possums have multiple occurrences of a single microsatellite repeat element within the Y-chromosome and among autosomal loci. We will compare variation between the Y-linked and non Y-linked loci within and among individual possums and use those comparisons to distinguish between recombinant and non- recombinant mutational mechanisms. These data will provide new insights into the mutational mechanisms that drive variation in these most important molecular markers.Read moreRead less
Sex in Dragons: Evolution of sex determination in reptiles. Australia is a leader in sex determination research with major advances in our understanding attributable to Australian researchers and laboratories. This project will contribute to our prestige as a nation capable of contributing cutting edge research directions and stimulating ideas in human sex determination. Moreover, many reptiles have temperature-dependent sex determination, and so would appear appallingly vulnerable to climate ch ....Sex in Dragons: Evolution of sex determination in reptiles. Australia is a leader in sex determination research with major advances in our understanding attributable to Australian researchers and laboratories. This project will contribute to our prestige as a nation capable of contributing cutting edge research directions and stimulating ideas in human sex determination. Moreover, many reptiles have temperature-dependent sex determination, and so would appear appallingly vulnerable to climate change. Our project, will bring improved understanding of sex determination in reptiles, identify evolutionary responses of reptiles to climate change, and assist by informing society on how we might manage this issue into the future conservation of these unique Australian reptiles. Read moreRead less