Signal transduction and the control of bacterial respiration by the NtrYX two component regulatory system. This proposal will define the structural and functional properties of the NtrYX two component signal transduction and define its role in the regulation of respiratory gene expression. The human pathogen Neisseria gonorrhoeae will be used as a model organism for a diverse range of 'oxidase positive' bacteria that possess NtrYX. The outcome will be a major contribution to the understanding of ....Signal transduction and the control of bacterial respiration by the NtrYX two component regulatory system. This proposal will define the structural and functional properties of the NtrYX two component signal transduction and define its role in the regulation of respiratory gene expression. The human pathogen Neisseria gonorrhoeae will be used as a model organism for a diverse range of 'oxidase positive' bacteria that possess NtrYX. The outcome will be a major contribution to the understanding of way in which respiratory gene expression is controlled in bacterial species for which Escherichia coli is not a suitable model. Read moreRead less
The selective elimination of mitochondria from yeast cells: regulation and molecular mechanism . For healthy cells the quality of the mitochondrion, the cellular power plant, must be maintained. The results of this research will contribute to an understanding of the molecular mechanism for the removal of mitochondria from the cell, and ultimately inspire strategies for the treatment of diseases that result from faulty mitochondria.
MECHANISMS OF PATHOLOGY AND NEW THERAPEUTIC OPTIONS FOR GAUCHER DISEASE AND OTHER LIPIDOSES
Funder
National Health and Medical Research Council
Funding Amount
$439,500.00
Summary
The sphingolipidoses are a subgroup of the more than 45 genetic disorders known collectively as lysosomal storage disorders (LSD). As a result of the deficiency of specific enzymes or proteins involved in the breakdown of sphingolipids (fats), there is an accumulation of this material in affected cells. These diseases can affect liver, spleen, kidney, bone and the central nervous system. Gaucher disease is the prototype for the sphingolipidoses and, in this project, we will use this disease as a ....The sphingolipidoses are a subgroup of the more than 45 genetic disorders known collectively as lysosomal storage disorders (LSD). As a result of the deficiency of specific enzymes or proteins involved in the breakdown of sphingolipids (fats), there is an accumulation of this material in affected cells. These diseases can affect liver, spleen, kidney, bone and the central nervous system. Gaucher disease is the prototype for the sphingolipidoses and, in this project, we will use this disease as a model for this group of disorders. Gaucher disease in the most prevalent LSD with an incidence of 1:56,00 births, worldwide there are approximately 2300 affected individuals born each year. Enzyme replacement therapy (ERT) for Gaucher disease has been successful in the treatment of the non-neuropathic form of the disease. However ERT is expensive ($200,000-400,000 pa). There are approximately 50 Australian patients undergoing ERT at a cost of at least $10 million per annum. However, due to the high cost of treatment, many people do not qualify for ERT, despite having serious medical problems. Worldwide, there are approximately 4000 people currently receiving ERT for Gaucher disease at a total drug cost of over $1.0 billion pa. However, based on birth rates and life expectancies there are over 80,000 Gaucher patients in the world. With the current cost of ERT it is likely that over 90% of these will never receive ERT. If therapy is to be made available for the majority of affected individuals, cheaper alternatives will be required. In this project we will use cellular models of Gaucher disease to study the processes leading to the disease and to develop alternative, cheaper therapies for this disease and other types of sphingolipidoses, for which no therapies currently exist.Read moreRead less
Heme oxygenase integrates cellular responses to oxygen stress. A deficiency in the protein heme oxygenase-1 causes severe biological consequences including retarded development, chronic inflammation and increased susceptibility to age-associated diseases. By illuminating how heme oxygenase-1 improves cell function the project will eventually assist in preventing or slowing the serious age-associated disorders.
How do cells regulate the synthesis and localisation of coenzyme Q? The aims of this project are to identify how cells regulate the synthesis and the distribution of coenzyme Q between different organelles, and how these processes are affected when cells experience various conditions of stress. Coenzyme Q is a fat-soluble molecule present in all cell membranes and essential for normal cell function. Despite this, relatively little is known about the systems that regulate the synthesis and cellul ....How do cells regulate the synthesis and localisation of coenzyme Q? The aims of this project are to identify how cells regulate the synthesis and the distribution of coenzyme Q between different organelles, and how these processes are affected when cells experience various conditions of stress. Coenzyme Q is a fat-soluble molecule present in all cell membranes and essential for normal cell function. Despite this, relatively little is known about the systems that regulate the synthesis and cellular location of coenzyme Q. The project plans to identify the genes and proteins required for coenzyme Q regulation of sub-cellular distribution in unstressed and stressed cells. In doing so, the project could provide a greater understanding of the ways cells maintain normal coenzyme Q levels and respond to stress.Read moreRead less
Redirecting Carbon Flow through Mesophyll and Bundle Sheath Cells of Sugarcane to Produce Poly-3-Hydroxybutyrate. This project is part of the National Priorities "Frontier Technologies for Building and Transforming Australian Industries." Using innovative plant metabolic engineering technologies combined with sophisticated computer modeling we are generating green plants that produce renewable, biodegradable, bioplastics possessing properties such that they are suitable replacements for petrol ....Redirecting Carbon Flow through Mesophyll and Bundle Sheath Cells of Sugarcane to Produce Poly-3-Hydroxybutyrate. This project is part of the National Priorities "Frontier Technologies for Building and Transforming Australian Industries." Using innovative plant metabolic engineering technologies combined with sophisticated computer modeling we are generating green plants that produce renewable, biodegradable, bioplastics possessing properties such that they are suitable replacements for petroleum-derived products in many applications. During the course of these studies, we are increasing our basic level of understanding of plant metabolism of important bioenergy crops. The production of renewable, bioplastics in sugarcane will help to diversify the Australian sugarcane industry by providing a value-added product with significant world-wide markets.Read moreRead less
Adaptive reprogramming of metabolism in regeneration. . Biologists have long been intrigued at the phenomenon of organ regeneration. Unlike most human organs, the liver exhibits the remarkable capacity to regenerate. Despite decades of research, the molecular underpinnings of liver regeneration are poorly understood. This research proposal aims to use zebrafish to elucidate the pathways involved in sensing injury and activating an adaptive transcriptional and metabolic response to orchestrate re ....Adaptive reprogramming of metabolism in regeneration. . Biologists have long been intrigued at the phenomenon of organ regeneration. Unlike most human organs, the liver exhibits the remarkable capacity to regenerate. Despite decades of research, the molecular underpinnings of liver regeneration are poorly understood. This research proposal aims to use zebrafish to elucidate the pathways involved in sensing injury and activating an adaptive transcriptional and metabolic response to orchestrate regeneration. Ultimately, this works aims to understand the metabolic requirements for regeneration. Expected outcomes include scholarly publications revealing fundamental principles of regeneration, new resources and pipelines for the research community as well as training for research students.Read moreRead less
Sleeping snails: investigating hypometabolism to reveal critical factors that aid life extension. The apparent state of eternal dormancy has fascinated people for hundreds of years. This project will explore new frontiers in life extension and snail control by defining those genes and peptides involved in snail hypometabolism. To achieve this, the project will interrogate the snails' natural state of hypometabolism called estivation.
Transcription-based Identification Of Insulin Resistance Subtypes
Funder
National Health and Medical Research Council
Funding Amount
$341,883.00
Summary
A key feature of type 2 diabetes is the failure of metabolic tissues such as muscle and fat to respond to normal levels of insulin. This 'insulin resistance' is caused by a number of mechanisms. We will use cutting-edge technology to identify small sets of genes that define each variety of insulin resistance. These gene sets will be used to diagnose sub-types of insulin resistance and will facilitate the development of personalised therapies to effectively treat individuals with type 2 diabetes.