Molecular Mechanisms Of Receptor Activation And Signalling
Funder
National Health and Medical Research Council
Funding Amount
$571,980.00
Summary
Fundamental to our ability to respond to both immediate and long-term environmental changes and stresses is the coordinated regulation of cellular functions by hormonal and neurotransmitter stimuli. The great majority of such stimuli are sensed by G-protein coupled receptors (GPCR), complex glycoprotein molecules on the surface of most cells that selectively bind and are activated by various hormones and neurotransmitters. Although GPCRs are a superfamily of proteins that now compromise several ....Fundamental to our ability to respond to both immediate and long-term environmental changes and stresses is the coordinated regulation of cellular functions by hormonal and neurotransmitter stimuli. The great majority of such stimuli are sensed by G-protein coupled receptors (GPCR), complex glycoprotein molecules on the surface of most cells that selectively bind and are activated by various hormones and neurotransmitters. Although GPCRs are a superfamily of proteins that now compromise several hundred distinct but structurally-related members, the molecular mechanisms involved in their activation and, thus, their regulation of vital cellular functions, remains unclear. Based on insights that we have gained from the development and characterisation of several alpha1-adrenergic receptor mutants, we have developed a model of receptor activation. In this application we are proposing to further test and to extend the hypotheses underlying this model. Importantly, the functions regulated by GPCR include vital responses, such as the maintenance of circulatory homeostasis by augmenting heart pump function and by constricting vascular smooth muscle to maintain blood pressure. In addition, disordered cellular regulation by GPCR has been implicated in a wide variety of diseases, including hypertension, congestive heart failure and cardiac hypertrophy. Thus, the studies detailed here to further understand the molecular mechanisms of receptor activation have broad implications for our knowledge of critical physiological control systems, and may lead to novel therapeutic approaches to treat a variety of diseases.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE0668382
Funder
Australian Research Council
Funding Amount
$1,000,000.00
Summary
e-Research Infrastructure for the Molecular and Materials Structure Sciences. Understanding molecular and materials structure in atomic detail is vital to a knowledge-based economy and a healthy society. The development of smart materials, nanotechnological devices, hydrogen storage materials, molecular switches, magnets and sensors, for example, depends on knowledge of three-dimensional atomic structure. Cures for illnesses such as SARS, AIDS and Alzheimer's disease and understanding the aging ....e-Research Infrastructure for the Molecular and Materials Structure Sciences. Understanding molecular and materials structure in atomic detail is vital to a knowledge-based economy and a healthy society. The development of smart materials, nanotechnological devices, hydrogen storage materials, molecular switches, magnets and sensors, for example, depends on knowledge of three-dimensional atomic structure. Cures for illnesses such as SARS, AIDS and Alzheimer's disease and understanding the aging process depends on knowledge of biomolecular structure. The deployment and development of automation-enhanced remote access to structural instruments through the web will greatly enhance Australian structure-based research, and make this science accessible to the public. Read moreRead less
Signalling Networks As Targets For Antibody Therapy In Glioma.
Funder
National Health and Medical Research Council
Funding Amount
$526,683.00
Summary
Antibodies are a major component of the bodies immune system that bind (i.e. stick) to foreign substances such as viruses. Once bound, these antibodies can activate other parts of the immune system, which help destroy the foreign substance. Analogous to the situation above, a number of institutions are testing antibodies that bind to cancer cells, in order to determine if they are able to destroy these cells. It is also possible to generate antibodies that bind to receptors on the surface of can ....Antibodies are a major component of the bodies immune system that bind (i.e. stick) to foreign substances such as viruses. Once bound, these antibodies can activate other parts of the immune system, which help destroy the foreign substance. Analogous to the situation above, a number of institutions are testing antibodies that bind to cancer cells, in order to determine if they are able to destroy these cells. It is also possible to generate antibodies that bind to receptors on the surface of cancer cells and block their function. If you target a receptor critical to the growth or survival of a cancer cell in this way, then swtiching-off this signal may inhibit tumor growth. In this proposal we plan to test a panel antibodies that recognize receptors important to the growth of brain cancer. Two of these antibodies have been generated and the other two will be made as part of this proposal. A key aspect of this proposal will be testing these antibodies in combination to determine how many receptors need to be targeted in order to get complete tumor regressions in animal models. Overall this work will help us identify new therapeutic strategies for the treatment of brain cancer. Finally, we will also analyze the way different receptors interact together in brain cancer cells.Read moreRead less
Surface Chemistry meets Cell Biology: Molecular Level Control of Surface Architecture for Cell Adhesion and Migration. Biotechnological applications such as tissue engineering, bone supports, implantable materials, cell assays and biosensors all require detailed knowledge of how cells interact with their environment. The proposed research aims to provide this knowledge by developing unique modified surfaces to investigate white blood cell migration and adhesion. Additional expected outcome will ....Surface Chemistry meets Cell Biology: Molecular Level Control of Surface Architecture for Cell Adhesion and Migration. Biotechnological applications such as tissue engineering, bone supports, implantable materials, cell assays and biosensors all require detailed knowledge of how cells interact with their environment. The proposed research aims to provide this knowledge by developing unique modified surfaces to investigate white blood cell migration and adhesion. Additional expected outcome will contribute to our understanding of the many fundamental cellular processes such as cell growth, differentiation and cell death as well as the molecular basis of diseases such as inflammation, cancer, cardiovascular diseases and wound healing. This research program will establish Australia as a leading force in this new research field.Read moreRead less
Cognitive Enhancement In Schizophrenia Via Selective Oestrogen Receptor Modulator.
Funder
National Health and Medical Research Council
Funding Amount
$396,380.00
Summary
Cognitive dysfunction in schizophrenia is resistant to treatment and related to poor community functioning and quality of life. In spite of the widely appreciated magnitude of the problem, there is still a critical gap in our knowledge concerning treatments to reverse these cognitive deficits. The proposed research is significant because it will clarify the role of hormones and genes in relation to cognitive deficits in schizophrenia and it may help patients improve their level of functioning.
The development of tuneable materials to allow the three-dimensional printing of cells. New low cost three-dimensional (3D) printers and reagents will be developed during this project to allow cancer biologists to print cells and polymers as more realistic 3D tissue models for biological assays. Such technology will be important for performing basic research into cancers as well as for providing better tools for drug testing.
Nanotherapeutics: nanoparticles with high specificity for the delivery and controlled release of drugs. This technology will deliver therapeutic drugs and/or MRI contrast agents to individual diseased cells with very high specificity and selectivity. The cells can be interogated to determine when they are "loaded" and the site of the "loaded" cells precisely determined. Drugs can be released photochemically. The administered dosage can be decreased with no loss of efficacy, and side effects re ....Nanotherapeutics: nanoparticles with high specificity for the delivery and controlled release of drugs. This technology will deliver therapeutic drugs and/or MRI contrast agents to individual diseased cells with very high specificity and selectivity. The cells can be interogated to determine when they are "loaded" and the site of the "loaded" cells precisely determined. Drugs can be released photochemically. The administered dosage can be decreased with no loss of efficacy, and side effects reduced. Read moreRead less
Biomagnification of the biotoxin BMAA in the environment. Using unique models and technics, the project aims to demonstrate that long-term exposure to the blue green algae toxin β-N-methylamino-l-alanine (BMAA) leads to uptake, accumulation and toxicity within the central nervous system. The risks for heath, mechanisms of contamination and toxicity of BMAA are very poorly understood. Algal blooms cost the Australian community more than $250 million each year and represent a major health issue fo ....Biomagnification of the biotoxin BMAA in the environment. Using unique models and technics, the project aims to demonstrate that long-term exposure to the blue green algae toxin β-N-methylamino-l-alanine (BMAA) leads to uptake, accumulation and toxicity within the central nervous system. The risks for heath, mechanisms of contamination and toxicity of BMAA are very poorly understood. Algal blooms cost the Australian community more than $250 million each year and represent a major health issue for human and fauna. This project aims to be the first to fully characterise BMAA mechanisms of contamination and neurotoxicity and to highlight the major environmental risk of exposure of human to BMAA. It also aims to develop new and unique detection and quantification tools for BMAA.Read moreRead less
A novel platform for the biosynthesis of commercially valuable saxitoxins. Saxitoxins are potent microbial toxins, which pose a significant threat to food and water quality. Highly pure saxitoxins are required for environmental monitoring and studies of cell physiology. Certain analogues have also shown promise as long-lasting and non-addictive pain blockers. However, the procurement of these compounds from natural sources is convoluted and unsustainable. This project aims to use the latest synt ....A novel platform for the biosynthesis of commercially valuable saxitoxins. Saxitoxins are potent microbial toxins, which pose a significant threat to food and water quality. Highly pure saxitoxins are required for environmental monitoring and studies of cell physiology. Certain analogues have also shown promise as long-lasting and non-addictive pain blockers. However, the procurement of these compounds from natural sources is convoluted and unsustainable. This project aims to use the latest synthetic biology techniques to characterise, modify and express saxitoxin biosynthesis pathways, thereby providing a sustainable source of toxin analogues of value to industry and research. This novel 'green technology' will benefit the environment, human health and the Australian economy.Read moreRead less