Regulation Of Human Arylamine N-acetyltransferase Transcription, Translation And Protein Stability
Funder
National Health and Medical Research Council
Funding Amount
$470,958.00
Summary
Individuals respond very differently to many drugs and other chemicals in the diet and workplace. This variation can be a significant complication in treating patients and in attempting to determine risk with exposure to toxins. Genetic differences between individuals are a common reason for this variation. However, many enzymes and other proteins in humans are controlled by environmental factors that can either increase their activity or inhibit it. In this study, we will investigate how the ac ....Individuals respond very differently to many drugs and other chemicals in the diet and workplace. This variation can be a significant complication in treating patients and in attempting to determine risk with exposure to toxins. Genetic differences between individuals are a common reason for this variation. However, many enzymes and other proteins in humans are controlled by environmental factors that can either increase their activity or inhibit it. In this study, we will investigate how the activity of an important family of enzymes (the acetyltransferases) varies between individuals as a result of environmental factors. We will look at the genes for each of the enzymes and learn about this control mechanism. We will also look careful at the structure of the proteins and determine how this may change when challenged with external stimuli. The expected outcome will be a better understanding of these important enzymes that are involved in the metabolism of many drugs, and also provide a means of determining how different individuals may respond to foreign chemicals and drugs that use these enzymes in the body for metabolism.Read moreRead less
Expression And Regulation Of Human Genes Central To Drug Disposition In The Brain
Funder
National Health and Medical Research Council
Funding Amount
$339,375.00
Summary
The study of the regulation of human genes is inherently difficult. It is difficult or impossible to gain access to many body tissues in either healthy or sick individuals to examine coordinated gene function (or dysfunction). This is particularly true for the brain, where live human tissue is unavailable. For this reason, it is often the case that we have a much better understanding of gene function in species such as rats and mice, the most common animal environments for biomedical research. H ....The study of the regulation of human genes is inherently difficult. It is difficult or impossible to gain access to many body tissues in either healthy or sick individuals to examine coordinated gene function (or dysfunction). This is particularly true for the brain, where live human tissue is unavailable. For this reason, it is often the case that we have a much better understanding of gene function in species such as rats and mice, the most common animal environments for biomedical research. However, findings in animals often fail to meaningfully mirror what occurs in man. To progress our understanding of human genes in brain we need to develop models that more faithfully reproduce the human situation in an environment that is amenable to both manipulation and close examination, such as the novel 'humanized' mouse models described in this application. This application deals with the genes that control enzymes belonging to the human cytochrome P450 3A (CYP3A) subfamily and the drug transporter MDR1. These genes are present in several tissues including liver, gut, lung and brain. They form the main disposal pathway for foreign chemicals such as drugs, environmental pollutants and some cancer causing chemicals. In addition they are involved in the breakdown of several important internally produced substances, such as steroid hormones. We postulate that altered formation of CYP3A enzymes and MDR1 in brain can have a dramatic impact on the action of many important drugs and may affect the way the brain responds in a behavioral sense to hormones, such as sex steroids. In addition, this work will provide a new and useful information relevant to the design and development of the plethora of drugs that act on the central nervous system.Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE230101652
Funder
Australian Research Council
Funding Amount
$434,404.00
Summary
Assessing climate risk for future food supply. The aim of this project is to assess the impacts of future disruptive climate events and disasters on Australia's food system. This will be achieved by developing a world-first Integrated Assessment Modelling Lab, a collaborative research platform for comprehensive assessment of the effects of extreme climate events (bushfires/drought/floods/cyclones) on Australia's food supply. The project will use this capability to assess impacts on Australia's n ....Assessing climate risk for future food supply. The aim of this project is to assess the impacts of future disruptive climate events and disasters on Australia's food system. This will be achieved by developing a world-first Integrated Assessment Modelling Lab, a collaborative research platform for comprehensive assessment of the effects of extreme climate events (bushfires/drought/floods/cyclones) on Australia's food supply. The project will use this capability to assess impacts on Australia's national and international supply chains, industry sectors and on socio-economic groups. The outcomes will offer opportunities to improve national responses to the changing climate and build resilience by designing adaptation plans to safeguard national and international food supply chains.Read moreRead less
Hydrological changes in Australia and the South Pacific. This project plans to use stalagmites from the South–West Pacific to generate continuous rainfall records for the last 2000 years. Stalagmites contain uncorrupted data that are not available in other archives, and provide unparalleled accurate chronologies. The spatial and temporal variations of the data may highlight the interplay of climate drivers, such as El Niño Southern Oscillation, and how they change the distribution of rainfall in ....Hydrological changes in Australia and the South Pacific. This project plans to use stalagmites from the South–West Pacific to generate continuous rainfall records for the last 2000 years. Stalagmites contain uncorrupted data that are not available in other archives, and provide unparalleled accurate chronologies. The spatial and temporal variations of the data may highlight the interplay of climate drivers, such as El Niño Southern Oscillation, and how they change the distribution of rainfall in the Pacific. This knowledge would increase our scientific understanding and enable better predictions of the recurrence of droughts and wet events in Australia.Read moreRead less
How will animals respond to climate change? A genomic approach. This research will identify the genetic basis by which Adélie penguins in Antarctica have been able to respond to a dramatic 10 degree increase in temperature. The research will help us understand the biology of climate adaptation.
In 2013 there were ~200 million clinical cases of malaria, causing ~600,000 deaths. All antimalarial drugs are now associated with malaria parasite resistance. Thus, new therapies are urgently needed, including new drugs to prevent this disease. We have made the exciting discovery that an existing antimalarial drug can kill malaria parasites in a unique, previously unknown, manner. Here, we will investigate how this occurs and develop new drug candidates for malaria prevention.
Integrating past ice sheet dynamics with palaeoclimate in the Weddell Sea sector to evaluate current and future change in Antarctica. This project will extend historical records of change and understand the complex linkages between Antarctic climate and ice sheet dynamics, thereby assisting in: (i) identifying the mechanisms of past and future ice sheet stability, and (ii) communicating the research outputs to the general public, helping scientific understanding.
Reconstructing changes in atmospheric circulation over the mid-latitudes of the Southern Hemisphere during the past 3000 years. The climate of the mid-latitudes of the southern hemisphere is of global significance and yet past changes have proved difficult to reconstruct due to the dearth of records. Working across the Southern Ocean region using tree rings, lake sediments and ice cores, the project will produce the first comprehensive reconstruction spanning the last 3000 years.
Validation Of Formyl Peptide Receptor (FPR)2 As A Target For New Anti-cancer Drugs
Funder
National Health and Medical Research Council
Funding Amount
$588,529.00
Summary
Treatment of breast and other cancers is making incremental improvements, but premature death from this disease and its recurrence in some women after a long period of remission are not adequately treated by current drugs. New work has identified a target called FPR2 that could be used to guide the development of novel drugs. The current project seeks to validate the new drug target, before resource intensive efforts are made to find suitable drugs.
Australian Laureate Fellowships - Grant ID: FL100100195
Funder
Australian Research Council
Funding Amount
$2,981,452.00
Summary
Tipping points in Records of Extreme Events in Australasia: Using the Past to Understand and Plan for Abrupt Future Climate Change. This project will generate the fundamental science outputs required to extend historical records of change and understand the complex linkages between Australian and global atmospheric, terrestrial and marine processes in the climate system, thereby assisting in: (i) identifying the mechanisms of past and future climate variability; (ii) developing and validating me ....Tipping points in Records of Extreme Events in Australasia: Using the Past to Understand and Plan for Abrupt Future Climate Change. This project will generate the fundamental science outputs required to extend historical records of change and understand the complex linkages between Australian and global atmospheric, terrestrial and marine processes in the climate system, thereby assisting in: (i) identifying the mechanisms of past and future climate variability; (ii) developing and validating methodologies for improved climate reconstruction and robust chronological frameworks; (iii) predicting the response of Australian ecosystems to future climate change; and (iv) communicating the research outputs to the general public and state, national and international decision makers, helping scientific understanding and aiding resource management.Read moreRead less