Melanotransferrin: A “Missing Link” And A Novel Pharmacological Target For Treatment
Funder
National Health and Medical Research Council
Funding Amount
$613,848.00
Summary
Despite >30 years of research, the precise function of the protein, melanotransferrin (MTf), is unknown. However, we have breakthrough evidence that MTf stimulates WNT signalling as a major driver in cancer progression. We will investigate this hypothesis, which will underpin new cancer therapies. Indeed, we designed a new class of drugs that target the WNT pathway via up-regulating the WNT inhibitor, NDRG1. This drug (DpC) inhibits MTf expression to block tumour cell growth and metastasis.
Reasons and Rationality. The project explains how we assess the truth and falsehood of everyday claims about what people have reason to do. It also explains what legitimizes our practice of praising and blaming people for their success and failure at doing what we think they have reason to do. In so doing it provides a foundation for both our ordinary practice of holding people responsible, and for the more institutionalised counterpart of this ordinary practice in the law.
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
Are flavonoids metabolic regulators of plant development? This project will investigate the mechanisms of action of flavonoids, which are abundant and diverse plant products contained in all fruits and vegetables. We have very little knowledge on the range of activities this large class of natural compounds has in plants. This research will investigate the role of flavonoids in regulating plant development to identify flavonoids and their target proteins and genes that could alter plant develo ....Are flavonoids metabolic regulators of plant development? This project will investigate the mechanisms of action of flavonoids, which are abundant and diverse plant products contained in all fruits and vegetables. We have very little knowledge on the range of activities this large class of natural compounds has in plants. This research will investigate the role of flavonoids in regulating plant development to identify flavonoids and their target proteins and genes that could alter plant development in specific ways to create improved crops. This project will also strengthen Australia's expertise in proteomics, an important tool for the advancement of knowledge and application in biotechnology.Read moreRead less
Expression and characterisation of nutrient transporters from the intracellular malaria parasite, Plasmodium falciparum. The malaria parasite invades the red blood cells of its host and this provides it with a safe haven in which to grow and replicate. Within the red blood cell, the parasite takes up nutrients and excretes metabolic wastes via specialised membrane transport proteins which are, as yet, very poorly understood. The sequencing of the malaria parasite genome has enabled us to ident ....Expression and characterisation of nutrient transporters from the intracellular malaria parasite, Plasmodium falciparum. The malaria parasite invades the red blood cells of its host and this provides it with a safe haven in which to grow and replicate. Within the red blood cell, the parasite takes up nutrients and excretes metabolic wastes via specialised membrane transport proteins which are, as yet, very poorly understood. The sequencing of the malaria parasite genome has enabled us to identify candidates for a wide variety of these proteins. The aim of this project is to establish systems in which the functional properties of these transporter proteins may be characterised in detail.Read moreRead less
The biology of arbovirus virulence and fitness in arthropod and vertebrate hosts in vivo. In Australia, Ross River virus (RRV) represents significant concern to human health. Between 1992-2005 more than 50,000 notifications of RRV infection have been reported. While not fatal, the disease is responsible for morbidity in the community/individual that can have both social and economic costs. The project has several national benefits. It will help elucidate whether there is any association between ....The biology of arbovirus virulence and fitness in arthropod and vertebrate hosts in vivo. In Australia, Ross River virus (RRV) represents significant concern to human health. Between 1992-2005 more than 50,000 notifications of RRV infection have been reported. While not fatal, the disease is responsible for morbidity in the community/individual that can have both social and economic costs. The project has several national benefits. It will help elucidate whether there is any association between RRV strain and increased risk of RRV transmission and/or occurrence of more severe cases of human disease. It will help develop technologies that can lead towards the identification of viral markers, which could provide new avenues in the design of novel antiviral strategies.
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The Role And Underlying Mechanisms Of Constitutional Epigenetic Silencing In Cancer Predisposition
Funder
National Health and Medical Research Council
Funding Amount
$218,617.00
Summary
Familial and young onset bowel and uterine cancer are usually caused by the inheritance of spelling mistakes in the genetic code within a set of cancer-protection genes. Recently, some patients were identified with their gene switched off by paralysing chemicals instead. This study aims to identify additional cancer cases with gene paralysis, determine if this arises in the presence or absence of a genetic change in front of the gene, and how gene paralysis is transmitted to the next generation.
A genomic and phenomic investigation of a mitochondrial glutathione transferase. The aim of this study is to understand of the genomics, structure and function of glutathione transferase Kappa (GSTK), a novel GST found in mitochondria. The investigations will achieve several outcomes. (1)an understanding of the organisation of GSTK gene(s) in humans and mice; (2) determination of the role of GSTK in mitochondria, by investigating the phenotype of knockout mice; (3) determination of the crysta ....A genomic and phenomic investigation of a mitochondrial glutathione transferase. The aim of this study is to understand of the genomics, structure and function of glutathione transferase Kappa (GSTK), a novel GST found in mitochondria. The investigations will achieve several outcomes. (1)an understanding of the organisation of GSTK gene(s) in humans and mice; (2) determination of the role of GSTK in mitochondria, by investigating the phenotype of knockout mice; (3) determination of the crystal structure of human GSTK; (4) An understanding of GSTK's substrate specificity, reaction kinetics and structure/function relationships. Since GSTK is confined to mitochondria, and may not be related to other GSTs, we may also identify novel functionsRead moreRead less
Trust and Distrust in Social Epistemic Networks. This project aims to discover critically-needed understandings of the social causes and consequences of ‘fake news’. It will do this by investigating and mapping the relationship between ‘epistemic vices’ and people’s acceptance of misinformation and disinformation (e.g. conspiracy theories). It will bring together approaches from experimental philosophy, natural language processing, social network analysis, and normative reflection to provide new ....Trust and Distrust in Social Epistemic Networks. This project aims to discover critically-needed understandings of the social causes and consequences of ‘fake news’. It will do this by investigating and mapping the relationship between ‘epistemic vices’ and people’s acceptance of misinformation and disinformation (e.g. conspiracy theories). It will bring together approaches from experimental philosophy, natural language processing, social network analysis, and normative reflection to provide new insights regarding distrust and intellectual vice, thus significantly advancing knowledge of the ‘dark side’ of social epistemology. Results will lead to urgently required guidance regarding the features of social networks that exacerbate or buffer against the manifestation of these vices.Read moreRead less
Enabling Technologies for Structural Genomics. New technologies will be developed to save time, money and effort in rapid preparation of protein samples for structural genomics. Systems will be devised for preparing sufficient isotope-labelled proteins for nuclear magnetic resonance spectroscopy without using living organisms, for efficiently identifying points at which proteins can be broken into smaller fragments with the right properties, and for joining the ends of proteins and peptides toge ....Enabling Technologies for Structural Genomics. New technologies will be developed to save time, money and effort in rapid preparation of protein samples for structural genomics. Systems will be devised for preparing sufficient isotope-labelled proteins for nuclear magnetic resonance spectroscopy without using living organisms, for efficiently identifying points at which proteins can be broken into smaller fragments with the right properties, and for joining the ends of proteins and peptides together to make them much more stable. This combination of technologies are widely applicable to current problems in protein chemistry, molecular biology, functional genomics and the medical sciences.Read moreRead less