New Imaging Agents for Neuronal Nicotinic Receptors. Recent advances in medical imaging technology such as Positron Emission Tomography (PET) and Single Photon Emission Computed Tomography (SPECT) have radically improved the diagnosis and treatment of a wide range of diseases. The aim of this project is to discover novel radio-ligands that selectively bind to neuronal nicotinic acetylcholine receptors. These ligands will have great potential for the imaging, diagnosis and study of neurodegenerat ....New Imaging Agents for Neuronal Nicotinic Receptors. Recent advances in medical imaging technology such as Positron Emission Tomography (PET) and Single Photon Emission Computed Tomography (SPECT) have radically improved the diagnosis and treatment of a wide range of diseases. The aim of this project is to discover novel radio-ligands that selectively bind to neuronal nicotinic acetylcholine receptors. These ligands will have great potential for the imaging, diagnosis and study of neurodegenerative diseases such as Alzheimer's disease. Read moreRead less
Radiolabelled MMP binding agents for the identification, quantification, and targeting of MMPs in central nervous system (CNS) disorders and tumours. Cancer and diseases of the central nervous system (CNS) represent two of the major health challenges facing Australia because of the aging population. In order to address these challenges we need to develop methods for identifying tumours and CNS diseases using non-invasive technologies and at an early stage so that treatments can be applied when t ....Radiolabelled MMP binding agents for the identification, quantification, and targeting of MMPs in central nervous system (CNS) disorders and tumours. Cancer and diseases of the central nervous system (CNS) represent two of the major health challenges facing Australia because of the aging population. In order to address these challenges we need to develop methods for identifying tumours and CNS diseases using non-invasive technologies and at an early stage so that treatments can be applied when they are most likely to work. In this project, we are developing new radiolabelled compounds that will enable the imaging of tumours, tumour metastases and CNS diseases states.Read moreRead less
O-GlcNAc-phosphorylation: a novel post-translational modification regulating vesicle recycling. We will determine a biological role for our discovery of a hybrid protein modification (both carbohydrate and phosphate) on a brain protein that is involved in nerve cell communication. If this modification is more widespread, then we will have discovered a new level of cellular regulation. This discovery is likely to have a broad benefit. It will advance the understanding of carbohydrate and phosphat ....O-GlcNAc-phosphorylation: a novel post-translational modification regulating vesicle recycling. We will determine a biological role for our discovery of a hybrid protein modification (both carbohydrate and phosphate) on a brain protein that is involved in nerve cell communication. If this modification is more widespread, then we will have discovered a new level of cellular regulation. This discovery is likely to have a broad benefit. It will advance the understanding of carbohydrate and phosphate modified proteins. For example, there may be consequences for the model of hyperphosphorylated and carbohydrate modified proteins involved in neurodegeneration. There will also be a targeted benefit. An improved understanding of the mechanism of neurotransmission will benefit in designing compounds to fight diseases of neurotransmission.Read moreRead less
Synthetic derivatives of capsaicin and gingerols as analgesics acting at the vanilloid receptor. This project aims to prepare alpha-hydroxyketones and gingerol derivatives acting at vanilloid (VR1) receptor with potential analgesic activity. These compounds will be tested for their ability to activate the VR1 receptor, desensitize the receptor and release neuropeptides associated with pain pathways. The development of these novel compounds will contribute towards understanding the mechanisms of ....Synthetic derivatives of capsaicin and gingerols as analgesics acting at the vanilloid receptor. This project aims to prepare alpha-hydroxyketones and gingerol derivatives acting at vanilloid (VR1) receptor with potential analgesic activity. These compounds will be tested for their ability to activate the VR1 receptor, desensitize the receptor and release neuropeptides associated with pain pathways. The development of these novel compounds will contribute towards understanding the mechanisms of VR1 receptor activation and provide information on how the VR1 receptor is regulated. We will determine and compare neurotoxicity of these compounds to capsaicin which is known to possess neurotoxic activity. The outcome of this project may result in effective agents for better pain management.
Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE100100010
Funder
Australian Research Council
Funding Amount
$720,000.00
Summary
A 5-D Correlative Imaging Platform: Combining the strengths of light and electron microscopy. This will be Australia's first dedicated five-dimensional multiphoton-microscopy platform, allowing observation of dynamic structures across different length and time scales under controlled temperatures, followed by high-resolution electron microscopy studies on the same samples. This platform will provide a unique characterisation tool to Australia's top-flight investigators, and so contribute to the ....A 5-D Correlative Imaging Platform: Combining the strengths of light and electron microscopy. This will be Australia's first dedicated five-dimensional multiphoton-microscopy platform, allowing observation of dynamic structures across different length and time scales under controlled temperatures, followed by high-resolution electron microscopy studies on the same samples. This platform will provide a unique characterisation tool to Australia's top-flight investigators, and so contribute to the nation's research priorities. It will enable: fundamental studies of cancer, neural diseases and immune disorders; the development of frontier technologies, such as smart nanomaterials, biosensors and targeted drug delivery; and applied research to help plants and soils adapt to climate variability, and to increase sustainable use of water.Read moreRead less
Free Radicals in Chemistry and Biology: A Computational Quantum Chemistry Investigation. This proposal aims to carry out state-of-the-art chemistry research using computers rather than traditional laboratory techniques. Free radicals, which have widespread importance in the multibillion dollar polymer and health industries, form the centrepiece of the proposal. These are highly reactive substances that are difficult to study by conventional experimental techniques but ideal to study using compu ....Free Radicals in Chemistry and Biology: A Computational Quantum Chemistry Investigation. This proposal aims to carry out state-of-the-art chemistry research using computers rather than traditional laboratory techniques. Free radicals, which have widespread importance in the multibillion dollar polymer and health industries, form the centrepiece of the proposal. These are highly reactive substances that are difficult to study by conventional experimental techniques but ideal to study using computers. The increased understanding of free radicals that will stem from this research may help in dealing with ageing, and afflictions such as hardening of the arteries and vitamin B12 deficiency. It will also result in the training at the highest level of new generations of chemists in this exciting field of "chemistry with computers".Read moreRead less
Computational Quantum Chemistry Study of Molecular Structures, Stabilities and Reactions. Computational quantum chemistry is revolutionizing the study and practice of chemistry. We will use state-of-the-art computer calculations to investigate chemical structures, stabilities and reactions, particularly for free radicals. Radicals are of great importance in chemistry, biology and polymer science, but are difficult to study experimentally. We will use the computer calculations to determine how ....Computational Quantum Chemistry Study of Molecular Structures, Stabilities and Reactions. Computational quantum chemistry is revolutionizing the study and practice of chemistry. We will use state-of-the-art computer calculations to investigate chemical structures, stabilities and reactions, particularly for free radicals. Radicals are of great importance in chemistry, biology and polymer science, but are difficult to study experimentally. We will use the computer calculations to determine how to make radicals more stable, how they react to produce polymers, how they cause damage to proteins, and how they are involved in helping vitamin B12 make reactions go faster. We will create new methodologies in order to reliably achieve these goals.Read moreRead less
Mechanisms and consequences of oxidation of glycosaminoglycans, proteins and proteoglycans by myeloperoxidase-derived oxidants. Atherosclerosis (hardening of the arteries) is responsible for the death of 40% of the population of developed, and developing, countries including Australia. Rupture of the fibrous cap of atherosclerotic lesions is responsible for most sudden deaths from heart disease and stokes, but is a poorly understood process. Evidence has been presented for a role for oxidation r ....Mechanisms and consequences of oxidation of glycosaminoglycans, proteins and proteoglycans by myeloperoxidase-derived oxidants. Atherosclerosis (hardening of the arteries) is responsible for the death of 40% of the population of developed, and developing, countries including Australia. Rupture of the fibrous cap of atherosclerotic lesions is responsible for most sudden deaths from heart disease and stokes, but is a poorly understood process. Evidence has been presented for a role for oxidation reactions in weakening the structure of lesions and making them prone to rupture. Little is known about the fundamental chemistry of such damage; this will be addressed in the proposed program. The data obtained will underpin the development of new preventative and protective strategies to minimise lesion rupture and deaths from this major disease.Read moreRead less
Mechanisms and consequences of myeloperoxidase-mediated damage to glycosaminoglycans, proteins and proteoglycans. Atherosclerosis (hardening of the arteries) is responsible for the death of 40% of the population of developed, and developing, countries including Australia. Rupture of the fibrous cap of atherosclerotic lesions is responsible for most sudden deaths from heart disease and stokes, but is a poorly understood process. Evidence has been presented for a role for oxidation reactions in we ....Mechanisms and consequences of myeloperoxidase-mediated damage to glycosaminoglycans, proteins and proteoglycans. Atherosclerosis (hardening of the arteries) is responsible for the death of 40% of the population of developed, and developing, countries including Australia. Rupture of the fibrous cap of atherosclerotic lesions is responsible for most sudden deaths from heart disease and stokes, but is a poorly understood process. Evidence has been presented for a role for oxidation reactions in weakening the structure of lesions and making them prone to rupture. Little is known about the fundamental chemistry of such damage; this will be addressed in the proposed program. The data obtained will underpin the development of new preventative and protective strategies to minimise lesion rupture and deaths from this major disease.Read moreRead less
Structural determination of respiratory membrane protein complexes by X-ray crystallography. Membrane proteins form only 0.3% of the available protein structures in the protein data bank (PDB), yet 30% of the proteins in the human genome and 50% of human drug targets are membrane proteins. We have managed to increase the success rate through rational screening and development of new crystallization screens, with downstream implications for basic and medical research. Results from this proposal w ....Structural determination of respiratory membrane protein complexes by X-ray crystallography. Membrane proteins form only 0.3% of the available protein structures in the protein data bank (PDB), yet 30% of the proteins in the human genome and 50% of human drug targets are membrane proteins. We have managed to increase the success rate through rational screening and development of new crystallization screens, with downstream implications for basic and medical research. Results from this proposal will receive international recognition and will encourage more research in this field, attracting international funding, and create new research opportunities. Read moreRead less