Many drugs modulate the function of proteins imbedded in cell membranes. Extensive research has been undertaken to better understand drug interactions with these proteins to improve drug therapies, but there has been relatively little progress in understanding the role of the cell membrane. This project will investigate how the cell membrane influences protein function and then use this information to develop novel drugs for the treatment of neurological disorders.
The Structural Basis For Glutamate Transporter Function
Funder
National Health and Medical Research Council
Funding Amount
$373,144.00
Summary
Glutamate transporters are vacuum cleaners in the brain that suck the neurotransmitter glutamate into cells. When the glutamate vacuum breaks down or becomes blocked, glutamate levels outside cells increase, leading to cell death in the brain. This process underlies the damage in many brain diseases including Alzheimer’s disease and stroke. The aim of this project is to understand the mechanism of the glutamate vacuum cleaner so we can develop therapeutics to fix it when it breaks down.
Control of transcription by the cardiac homeodomain protein Nkx2-5. The transcriptional regulatory protein Nkx2-5, a member of the homeodomain superfamily, is essential for heart development and mutations in the human gene cause congenital heart disease. We seek to define the molecular mechanisms that regulate the transcriptional activity of Nkx2-5. We have previously identified a transcriptional activation domain in the C-terminal region that is bipartite in nature and conserved among Nkx2-5 ....Control of transcription by the cardiac homeodomain protein Nkx2-5. The transcriptional regulatory protein Nkx2-5, a member of the homeodomain superfamily, is essential for heart development and mutations in the human gene cause congenital heart disease. We seek to define the molecular mechanisms that regulate the transcriptional activity of Nkx2-5. We have previously identified a transcriptional activation domain in the C-terminal region that is bipartite in nature and conserved among Nkx2-5 proteins from diverse species. We will characterise the consequences of mutations in this domain in mouse models and search for interacting proteins. Results will advance our understanding of gene regulation in the context of heart disease.Read moreRead less
Metalloproteins and metalloenzymes. Most of the chemical reactions and physical movements in living systems are carried out by proteins. The information for producing proteins from amino acids is stored in the genes, but many biological processes depend on additional atoms or molecules ('cofactors') that are added to a protein after it is assembled. For example, more than 30% of all proteins contain metal atoms which are essential for their function. We are studying the structures of such meta ....Metalloproteins and metalloenzymes. Most of the chemical reactions and physical movements in living systems are carried out by proteins. The information for producing proteins from amino acids is stored in the genes, but many biological processes depend on additional atoms or molecules ('cofactors') that are added to a protein after it is assembled. For example, more than 30% of all proteins contain metal atoms which are essential for their function. We are studying the structures of such metalloproteins and metalloenzymes so that we can better understand their activities with long term aims of creating new molecules for biotechnology and/or drugs.Read moreRead less
Functional Genomics and Host Cell Specificity of Herpesviruses. Herpesviruses cause severe diseases in many species, but research on their large DNA genomes has been difficult due to the need to use animal cell cultures for the generation of virus mutants. The cloning of complete herpesvirus genomes as Bacterial Artificial Chromosomes (BACs) has revolutionized herpesvirus genomics, and it is now possible to examine herpesvirus gene functions in unprecedented detail using elegant new mutation tec ....Functional Genomics and Host Cell Specificity of Herpesviruses. Herpesviruses cause severe diseases in many species, but research on their large DNA genomes has been difficult due to the need to use animal cell cultures for the generation of virus mutants. The cloning of complete herpesvirus genomes as Bacterial Artificial Chromosomes (BACs) has revolutionized herpesvirus genomics, and it is now possible to examine herpesvirus gene functions in unprecedented detail using elegant new mutation techniques. The project, based on two related equine herpesviruses, will identify new targets for antiviral drugs or vaccines. These herpesvirus BAC systems represent frontier science that greatly facilitates the study of links between genome and phenome.Read moreRead less
Understanding and changing the mechanism of an enzyme: converting a peptidase to a phosphotriesterase. Enzymes have the ability to catalyse biological reactions rapidly as a consequence of their unique three-dimensional structures. We seek to define the structures of a family of metalloenzymes that are required in most living organisms to activate hormones, degrade unwanted proteins or recycle the protein building blocks for further synthesis. We shall use this information to enhance a second ....Understanding and changing the mechanism of an enzyme: converting a peptidase to a phosphotriesterase. Enzymes have the ability to catalyse biological reactions rapidly as a consequence of their unique three-dimensional structures. We seek to define the structures of a family of metalloenzymes that are required in most living organisms to activate hormones, degrade unwanted proteins or recycle the protein building blocks for further synthesis. We shall use this information to enhance a second function of these enzymes, namely their ability to break down organophosphorus-containing insecticides and nerve agents. Ultimately, the structural information resulting from this project may be used in drug design to regulate blood pressure and in engineering proteins for bioremediation.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE0882512
Funder
Australian Research Council
Funding Amount
$400,000.00
Summary
Advanced high throughput functional genomics and gene mapping. Infrastructure requested will expand the capacity of researchers in NSW to undertake experiments using state-of-the-art technologies based on the recent advances in genomic and proteomic analysis. It will ensure the retention of leading researchers in the exciting areas of functional genomics and systems biology as contribute to biomolecular research in medicine, agriculture and environmental biology, thereby providing major benefit ....Advanced high throughput functional genomics and gene mapping. Infrastructure requested will expand the capacity of researchers in NSW to undertake experiments using state-of-the-art technologies based on the recent advances in genomic and proteomic analysis. It will ensure the retention of leading researchers in the exciting areas of functional genomics and systems biology as contribute to biomolecular research in medicine, agriculture and environmental biology, thereby providing major benefits to the wider community. The application aims to enhance existing genomic technologies by adding platforms that will increase the scope of experiments that can be performed as well as providing automation and increased capacity to handle the increasing demand for these techniquesRead moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE0989147
Funder
Australian Research Council
Funding Amount
$950,000.00
Summary
Advanced high throughput genomics facility for biological, medical, agricultural, environmental and evolutionary research. Infrastructure requested will expand the capacity of researchers in NSW/NT to undertake environmental, medical and evolutionary studies using state-of-the-art technologies based on the recent advances in DNA sequencing analyses. It will ensure the retention of leading researchers in the exciting areas of genomics and Systems Biology and make a significant contribution to bi ....Advanced high throughput genomics facility for biological, medical, agricultural, environmental and evolutionary research. Infrastructure requested will expand the capacity of researchers in NSW/NT to undertake environmental, medical and evolutionary studies using state-of-the-art technologies based on the recent advances in DNA sequencing analyses. It will ensure the retention of leading researchers in the exciting areas of genomics and Systems Biology and make a significant contribution to biomolecular research in medicine, agriculture and environmental biology, thereby providing major benefits to the wider community. The application will enhance existing genomic technologies by substantially increasing the scope of experiments that can be performed leading to important advances in gene discovery.Read moreRead less
Specific gene inhibition through functional genomics and high through-put small molecule screening. This project will utilise functional genomic technologies in an attempt to identify genes in childhood neuroblastoma as potential candidates for the future development of molecular-targeted gene therapy. By screening large 'libraries' of chemical compounds, we aim to identify compounds with the ability to specifically inhibit these gene targets. This project will therefore define novel molecular t ....Specific gene inhibition through functional genomics and high through-put small molecule screening. This project will utilise functional genomic technologies in an attempt to identify genes in childhood neuroblastoma as potential candidates for the future development of molecular-targeted gene therapy. By screening large 'libraries' of chemical compounds, we aim to identify compounds with the ability to specifically inhibit these gene targets. This project will therefore define novel molecular targets and possibly facilitate the future development of new therapeutic approaches to treating neuroblastoma. In addition, the project will develop know-how that can be utilised by both the industry partner and the broader research community and will introduce to Australian science novel techniques and skills. Read moreRead less
The structure and function of dihydroorotase - an enzyme essential for pyrimidine biosynthesis. Malaria has recently re-emerged as one of the major life threatening diseases worldwide. With increasing travel and climate change, malaria is increasingly endangering Australians at home and abroad. Our work aims to provide the basis for the rational design of a new class of anti-malarial drugs by the systematic and thorough analysis of an essential enzyme in the malarial parasite.