The Analgesic Evaluation Of Novel Natural Products From The Australian Plant Barringtonia Acutangula
Funder
National Health and Medical Research Council
Funding Amount
$174,500.00
Summary
This project aims to evaluate the analgesic activity of several novel natural products that have been isolated from the Australian plant Barringtonia acutangula. An Australian Aboriginal tribe have been known to use B. acutangula aqueous bark extracts for its analgesic properties. Griffith University researchers have confirmed this biological activity in the crude aqueous bark extract. A large scale extraction and isolation process will obtain the novel compounds in sufficient quantities that wi ....This project aims to evaluate the analgesic activity of several novel natural products that have been isolated from the Australian plant Barringtonia acutangula. An Australian Aboriginal tribe have been known to use B. acutangula aqueous bark extracts for its analgesic properties. Griffith University researchers have confirmed this biological activity in the crude aqueous bark extract. A large scale extraction and isolation process will obtain the novel compounds in sufficient quantities that will allow for their pharmacological evaluation as potential analgesic drugs.Read moreRead less
Examination Of The Molecular Pharmacology Of Anthracyclines Induced Via Their Interaction With Iron
Funder
National Health and Medical Research Council
Funding Amount
$618,401.00
Summary
Anthracyclines are highly effective anti-cancer drugs, but their use is limited by toxic effects on the heart. This is thought to be due to these drugs directly binding iron (Fe). Indeed, we showed that anthracyclines induced marked changes in the way heart cells utilise Fe (DR1-3, 38; Mol. Pharmacol. 2002, 2003, 2004, 2005). We were the first to show that anthracyclines prevent Fe release from the criticial Fe storage protein ferritin. This prevents the use of Fe for vital processes eg. DNA and ....Anthracyclines are highly effective anti-cancer drugs, but their use is limited by toxic effects on the heart. This is thought to be due to these drugs directly binding iron (Fe). Indeed, we showed that anthracyclines induced marked changes in the way heart cells utilise Fe (DR1-3, 38; Mol. Pharmacol. 2002, 2003, 2004, 2005). We were the first to show that anthracyclines prevent Fe release from the criticial Fe storage protein ferritin. This prevents the use of Fe for vital processes eg. DNA and haem synthesis. Hence, this effect probably contributes to the cytotoxic activity of anthracyclines on the heart. We showed that novel drugs developed in my lab that bind Fe called chelators show high activity in animals (DR4) and prevent anthracycline-mediated Fe accumulation in ferritin. Importantly, Fe chelators have been shown to inhibit anthracycline-mediated cardiotoxicity. Indeed, the clinically used cardioprotective agent, ICRF-187, is actually an Fe chelator (5, DR6). However, ICRF-187 is not totally successful in terms of its cardioprotective effects and can cause myelosuppression (5, DR6). While the clinically used chelator, desferrioxamine (DFO), can prevent anthracycline-mediated cardiotoxicity, its poor membrane permeability limits its effectiveness. Our chelators are highly permeable and overcome the disadvantages of DFO (DR4). Thus, they are vital to examine for preventing anthracycline-mediated cardiotoxicity. In this proposal we will examine the changes in Fe metabolism induced by anthracyclines and test the hypothesis that novel Fe chelators may prevent the cardiotoxicity of these agents. We also aim to be the first to assess if preparation of anthracyclines which cannot bind iron prevents their cardiotoxicity. This will be done by preparing metal complexes of these drugs which prevent Fe-binding eg. anthracycline-zinc complexes. These studies are important for the development of less cardiotoxic forms of these very useful anti-tumour agents.Read moreRead less
Pharmacology Of Potential Anti-Tumour Agents: Iron Chelators Of The BpT Class
Funder
National Health and Medical Research Council
Funding Amount
$585,455.00
Summary
Pharmacology of Potential Anti-Tumour Agents: Iron Chelators of the BpT Class Cancer cells have a high iron requirement for DNA synthesis and many clinical trials showed Fe chelators are effective anti-cancer drugs. Their potential to act as anti-tumour agents has been confirmed by the entrance of Triapine into widespread NCI clinical trials. In this NHMRC Renewal, we will perform pharmacological and preclinical studies to promote the development of BpT chelators as novel anti-tumour agents.
Transdermal penetration of corticosteroids in the dog. Topical application of corticosteroids enhances drug concentration and effectiveness in the treatment of skin diseases. Most topical corticosteroid preparations have been developed for human use and are poorly efficacious or promote a high incidence of adverse effects in dogs. This project will characterize corticosteroid penetration through canine skin to permit the development of suitable topical formulations to more effectively control ....Transdermal penetration of corticosteroids in the dog. Topical application of corticosteroids enhances drug concentration and effectiveness in the treatment of skin diseases. Most topical corticosteroid preparations have been developed for human use and are poorly efficacious or promote a high incidence of adverse effects in dogs. This project will characterize corticosteroid penetration through canine skin to permit the development of suitable topical formulations to more effectively control skin diseases in the dog. Skin diseases are a significant problem in veterinary science and this project will not only provide an effective therapeutic option, but also reduce animal (and client) distress when suffering skin disease and/or adverse effects from traditional therapy.Read moreRead less
Mobile DNA activity in the mammalian primordial germline. Early in pregnancy, a handful of cells in the embryo become primordial germ cells (PGCs). These PGCs will eventually give rise to sperm or egg cells, representing a critical inter-generational genetic link. Mobile DNA sequences target PGCs to create new heritable genetic changes. This proposal aims to analyse the activity, regulation, and consequences of mobile DNA activity in PGCs. This project expects to generate significant knowledge a ....Mobile DNA activity in the mammalian primordial germline. Early in pregnancy, a handful of cells in the embryo become primordial germ cells (PGCs). These PGCs will eventually give rise to sperm or egg cells, representing a critical inter-generational genetic link. Mobile DNA sequences target PGCs to create new heritable genetic changes. This proposal aims to analyse the activity, regulation, and consequences of mobile DNA activity in PGCs. This project expects to generate significant knowledge about the origins of mammalian genetic diversity. Expected outcomes include enhanced national and international collaborations across disciplines and new experimental systems. The expected benefit is an enhanced understanding of the mutational processes underlying genetic diversity and disease in mammals.Read moreRead less
Determining principles for successful episode retrieval of repeated events. This project aims to develop the first-ever set of explanatory principles for how people successfully retain and retrieve individual episode memories from repeated experiences (e.g., one occurrence of a routine social encounter or job-related activity). By deepening our understanding of how memory works, this new knowledge is expected to lay the foundation for interview guidance and ongoing research aimed at enhancing th ....Determining principles for successful episode retrieval of repeated events. This project aims to develop the first-ever set of explanatory principles for how people successfully retain and retrieve individual episode memories from repeated experiences (e.g., one occurrence of a routine social encounter or job-related activity). By deepening our understanding of how memory works, this new knowledge is expected to lay the foundation for interview guidance and ongoing research aimed at enhancing the proficiency of investigations into matters that rely on detailed and accurate accounts of specific episodes. This includes workplace or traffic accident investigations, infectious disease contact tracing, as well as prosecution of repeated sexual offences.Read moreRead less
Foundations of a good egg: correctly transitioning from mitosis to meiosis. Production of viable offspring is essential to the survival of any species. In all sexually reproducing species, this requires a unique cell type, the germ cell. Germ cells undergo a special type of cell division, called meiosis, so that they can eventually produce gametes (sperm in males and eggs in females). This project aims to discover how germ cells halt the standard form of cell division, called mitosis, and initia ....Foundations of a good egg: correctly transitioning from mitosis to meiosis. Production of viable offspring is essential to the survival of any species. In all sexually reproducing species, this requires a unique cell type, the germ cell. Germ cells undergo a special type of cell division, called meiosis, so that they can eventually produce gametes (sperm in males and eggs in females). This project aims to discover how germ cells halt the standard form of cell division, called mitosis, and initiate meiotic division instead. It is important to understand all the fundamental processes that occur during normal germ cell development so that, in the future, we can use this knowledge to support agricultural advances, rescue endangered species and solve human problems such as infertility and genetic disease.Read moreRead less
Novel pharmacological agents to target stroke-induced brain injury. There is a looming stroke epidemic in Australia. 72% of Australian stroke sufferers are over the age of 65 and whereas in 1997 only 12% of Australians were in that age group, by 2030 that number will have increased to 23%. There is an urgent need for novel therapies. This project will aid the development of a novel anti-stroke therapy.
Discovery Early Career Researcher Award - Grant ID: DE120101666
Funder
Australian Research Council
Funding Amount
$375,000.00
Summary
Endogenous bone regenerative technique to repair hard tissue defects in congenital craniofacial clefts. This project aims to develop an endogenous bone regenerative technique to repair the bony defects in congenital craniofacial clefts, through stimulating patients' latent self-repair mechanisms and reviving their innate capacity for regeneration. The novel technique would replace the existing and controversial surgical bone grafting method.
Mechanisms that control the inheritance of mitochondrial DNA mutations. How do humans and other organisms prevent the accumulation of dangerous mitochondrial genome (mtDNA) mutations across generations? This Project aims to uncover the cellular and molecular pathways that help prevent the inheritance of mtDNA mutations to offspring by employing cutting-edge genetic technologies that the laboratory has recently developed in the germline of an animal model system. This Project will generate new kn ....Mechanisms that control the inheritance of mitochondrial DNA mutations. How do humans and other organisms prevent the accumulation of dangerous mitochondrial genome (mtDNA) mutations across generations? This Project aims to uncover the cellular and molecular pathways that help prevent the inheritance of mtDNA mutations to offspring by employing cutting-edge genetic technologies that the laboratory has recently developed in the germline of an animal model system. This Project will generate new knowledge in the area of mitochondrial genetics and evolution. Expected outcomes include the development of new theories for mtDNA inheritance, which should provide significant benefits for agricultural breeding programs and the interpretation of mtDNA inheritance patterns in the human population.Read moreRead less