The basis of recognition and disposal of dysfunctional proteins by clusterin. When proteins become damaged they can precipitate. A blood protein called clusterin prevents precipitation of damaged proteins. Clusterin does this by forming complexes with the damaged proteins. Clusterin is the first blood protein known to do this. We will discover which parts of clusterin are responsible for this activity. We will also discover whether cells can take up and dispose of the complexes of clusterin and ....The basis of recognition and disposal of dysfunctional proteins by clusterin. When proteins become damaged they can precipitate. A blood protein called clusterin prevents precipitation of damaged proteins. Clusterin does this by forming complexes with the damaged proteins. Clusterin is the first blood protein known to do this. We will discover which parts of clusterin are responsible for this activity. We will also discover whether cells can take up and dispose of the complexes of clusterin and damaged proteins. This work is important because some diseases (eg, Alzheimers disease) involve the toxic effects of abnormal protein precipitation. Understanding how clusterin works may help in developing better treatments for these diseases.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE0668534
Funder
Australian Research Council
Funding Amount
$770,000.00
Summary
High resolution bioanalytical Fourier transform mass spectrometer combined with liquid chromatograph. This project extends a network of advanced technology for bioanalysis that enables discoveries in biotechnology, molecular medicine and biochemistry. The proposed equipment includes the most powerful mass spectrometer (MS) currently available for bioanalysis to complement an existing network of instruments at four universities in Sydney. These include 3 of 4 nodes of the Australian Proteome Anal ....High resolution bioanalytical Fourier transform mass spectrometer combined with liquid chromatograph. This project extends a network of advanced technology for bioanalysis that enables discoveries in biotechnology, molecular medicine and biochemistry. The proposed equipment includes the most powerful mass spectrometer (MS) currently available for bioanalysis to complement an existing network of instruments at four universities in Sydney. These include 3 of 4 nodes of the Australian Proteome Analysis Facility (APAF). The new technology is a missing link in bioanalytical capability where other instruments are not sufficiently sensitive. The instrument will be managed by MS specialists at the Bioanalytical Mass Spectrometry Facility at UNSW (www.bmsf.unsw.edu.au) where access by and training of users is well established.Read moreRead less
The role of intracellular calcium stores in cardiac pacemaking. The spontaneous firing of pacemaker cells is central to regulation of the cardiovascular system particularly during exercise. The discovery that pacemaker cell function is modulated in part by calcium ions will change our understanding of the changes in heart rate during exercise and in diseases which affect the pacemaker cells. Better understanding of the way in which spontaneous activity of these cells is regulated is the key to ....The role of intracellular calcium stores in cardiac pacemaking. The spontaneous firing of pacemaker cells is central to regulation of the cardiovascular system particularly during exercise. The discovery that pacemaker cell function is modulated in part by calcium ions will change our understanding of the changes in heart rate during exercise and in diseases which affect the pacemaker cells. Better understanding of the way in which spontaneous activity of these cells is regulated is the key to controlling or modifying their function.Read moreRead less
Chromera velia - a new organism for understanding malaria and related parasitic diseases. Malaria and related parasitic diseases cause millions of deaths annually. Chromera velia is a recently discovered organism that was isolated from Australian corals and is the closest known relative to these parasites. Chromera is able to photosynthesis and live in the absence of a host, making it an excellent organism for developing antimalarial drugs. In this project we will determine key features of Chro ....Chromera velia - a new organism for understanding malaria and related parasitic diseases. Malaria and related parasitic diseases cause millions of deaths annually. Chromera velia is a recently discovered organism that was isolated from Australian corals and is the closest known relative to these parasites. Chromera is able to photosynthesis and live in the absence of a host, making it an excellent organism for developing antimalarial drugs. In this project we will determine key features of Chromera ecology, morphology, genetics and biochemistry. The resulting data will allow us to exploit Chromera as a model for developing anti-parasitic drugs and for understanding parasite evolution. Read moreRead less
Zinc finger domains as scaffolds for protein engineering. While great advances have been made in pharmaceutical design and discovery, it is clear that new types of drugs are needed for the better management of a wide range of diseases (e.g. cancers, autoimmune diseases, viral infections). Many of these diseases arise from inappropriate interactions between intracellular biological macromolecules. My aim is to develop a range of novel therapeutic proteins based on naturally existing zinc-binding ....Zinc finger domains as scaffolds for protein engineering. While great advances have been made in pharmaceutical design and discovery, it is clear that new types of drugs are needed for the better management of a wide range of diseases (e.g. cancers, autoimmune diseases, viral infections). Many of these diseases arise from inappropriate interactions between intracellular biological macromolecules. My aim is to develop a range of novel therapeutic proteins based on naturally existing zinc-binding protein domains with the goal of selectively blocking these inappropriate interactions. Additionally, these engineered proteins have potential uses as biochemical tools such as to help delineate the functions of natural proteins with no known functions.Read moreRead less
New Surfaces for the Control of Endothelial Cell Function: Application in the Design of Biocompatible Stents. Using dewetting of thin polymer films, the present proposal will develop new structured biocompatible surfaces with controlled chemistry and topography, which will allow the growth of a normal (non-activated) monolayer of endothelial cells. Sophisticated molecular parameters will be used to assess that endothelial cells maintain their normal quiescent phenotype. The project sets the grou ....New Surfaces for the Control of Endothelial Cell Function: Application in the Design of Biocompatible Stents. Using dewetting of thin polymer films, the present proposal will develop new structured biocompatible surfaces with controlled chemistry and topography, which will allow the growth of a normal (non-activated) monolayer of endothelial cells. Sophisticated molecular parameters will be used to assess that endothelial cells maintain their normal quiescent phenotype. The project sets the ground work for the design of improved, more biocompatible structured stents to minimise the abnormal growth of cells on and around the stent, thereby reducing the occurrence of vascular complications. Thus this research could improve the success rate of stents implanted into patients with cardiovascular disease and reduce health costs.Read moreRead less
The role of intracellular calcium in fibre-type specific gene expression in skeletal muscle. Muscles contain different fibre types whose composition can be changed by activity. The aim of this proposal is to identify the intracellular mechanisms which control fibre type. Our hypothesis is that different patterns of intracellular calcium determine the pattern of gene expression which determines fibre type. Understanding how gene expression is regulated is a central issue in biology.
Stuctural analysis of RNA polymerase elongation complexes. RNA polymerase (RNAP) is an essential enzyme in all living cells. Its role is to convert the genetic information stored in genes into a message that can be converted into protein. Many additional factors are required to ensure that this enzyme functions correctly in the cell. The aim of this project is to obtain structural information on a bacterial RNAP complexed with an essential transcription factor called NusA. Using this information ....Stuctural analysis of RNA polymerase elongation complexes. RNA polymerase (RNAP) is an essential enzyme in all living cells. Its role is to convert the genetic information stored in genes into a message that can be converted into protein. Many additional factors are required to ensure that this enzyme functions correctly in the cell. The aim of this project is to obtain structural information on a bacterial RNAP complexed with an essential transcription factor called NusA. Using this information, plus data already obtained on the structure of this enzyme complexed with another essential factor called sigma, we will design small molecules to inhibit the interaction of these essential factors with polymerase. These molecules will serve as leads for the development of new antibiotics.Read moreRead less
Plasmid maintenance and interactions with the host cell and its genome. Plasmids are extrachromosomal genetic elements that play a central role in the evolution of bacteria. They are the most dynamic component of the bacterial genome, augmenting the host chromosome by conferring a range of significant phenotypes that facilitate environmental adaptation. This project aims to elucidate fundamental aspects of the relationship between plasmids and their bacterial hosts. Significant outcomes include ....Plasmid maintenance and interactions with the host cell and its genome. Plasmids are extrachromosomal genetic elements that play a central role in the evolution of bacteria. They are the most dynamic component of the bacterial genome, augmenting the host chromosome by conferring a range of significant phenotypes that facilitate environmental adaptation. This project aims to elucidate fundamental aspects of the relationship between plasmids and their bacterial hosts. Significant outcomes include understanding the molecular basis of efficient plasmid inheritance in bacterial populations, and exploration of the innovative hypothesis that plasmids modulate expression of the host chromosome, a possibility that would profoundly alter our view of how plasmids influence host phenotype.Read moreRead less
Quantitative Brain Dynamics. This proposal will benefit Australia through unique and fundamental contributions to understanding brain dynamics via the development of innovative approaches and technologies. It will contribute to the national priority goals of Breakthrough Science, Frontier Technologies, and Promoting an Innovation Culture and Economy. Science outcomes will include improved understanding and probing of brain self-organization, dynamics, and function, including unique contributio ....Quantitative Brain Dynamics. This proposal will benefit Australia through unique and fundamental contributions to understanding brain dynamics via the development of innovative approaches and technologies. It will contribute to the national priority goals of Breakthrough Science, Frontier Technologies, and Promoting an Innovation Culture and Economy. Science outcomes will include improved understanding and probing of brain self-organization, dynamics, and function, including unique contributions to understanding alertness and the foundations of vision. These outcomes will be applied to develop new technologies for brain imaging and monitoring.Read moreRead less