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Linkage Infrastructure, Equipment And Facilities - Grant ID: LE0453832
Funder
Australian Research Council
Funding Amount
$550,910.00
Summary
New directions in biomolecular mass spectrometry. The combined UoW/ANU mass spectrometry facility supports a range of research projects in high priority areas including proteomics, mechanisms of aging, anticancer drugs and pathogenicity. The facility has several key deficiencies: 1) the ability to study very high molecular weight biomolecular complexes, 2) the ability to study ion-molecule interactions that have implications in mechanisms of chemistry in nature, and 3) researchers at ANU lack es ....New directions in biomolecular mass spectrometry. The combined UoW/ANU mass spectrometry facility supports a range of research projects in high priority areas including proteomics, mechanisms of aging, anticancer drugs and pathogenicity. The facility has several key deficiencies: 1) the ability to study very high molecular weight biomolecular complexes, 2) the ability to study ion-molecule interactions that have implications in mechanisms of chemistry in nature, and 3) researchers at ANU lack essential walk-up access to high sensitivity protein sequence analysis (MS/MS). The placement of resources that address these deficiencies in one geographical region and collaboration between these institutions will produce a research interaction unique in Australia.Read moreRead less
Theoretical studies of molecular mechanisms of abnormal protein aggregation. Many proteins undergo conformational change and association as part of their physiological behavior. However, some proteins share a tendency to abnormal aggregation and form amyloid fibrils leading to disorders such as Alzheimer's and variant Creutzfeldt-Jacob diseases. Insulin, one such protein, has a high propensity to aggregate and form fibrils creating difficulties in preparation, storage and application. Using adva ....Theoretical studies of molecular mechanisms of abnormal protein aggregation. Many proteins undergo conformational change and association as part of their physiological behavior. However, some proteins share a tendency to abnormal aggregation and form amyloid fibrils leading to disorders such as Alzheimer's and variant Creutzfeldt-Jacob diseases. Insulin, one such protein, has a high propensity to aggregate and form fibrils creating difficulties in preparation, storage and application. Using advanced theoretical modelling techniques we will gain insight into the molecular mechanism of fibrillation by investigating the formation of insulin aggregates. An improved understanding of the essential mechanism of protein aggregation will allow the rational design of new drugs.Read moreRead less
Understanding the cardioprotective effects of flavonols. Heart attack and stroke are a major cause of death and disablement in Australia. Current therapies do not treat the underlying causes of these diseases. In this project we will investigate a promising new drug treatment for these diseases and will determine how this poorly understood drug acts to reduce damage to the heart. This project will lead to new treatments for cardiovascular diseases and will enhance our understanding of the causes ....Understanding the cardioprotective effects of flavonols. Heart attack and stroke are a major cause of death and disablement in Australia. Current therapies do not treat the underlying causes of these diseases. In this project we will investigate a promising new drug treatment for these diseases and will determine how this poorly understood drug acts to reduce damage to the heart. This project will lead to new treatments for cardiovascular diseases and will enhance our understanding of the causes of these disease states.Read moreRead less
Targeting DNA with Dynamic Combinatorial Chemistry. The interaction of molecules with DNA, the molecule that controls genetic information, is fundamental to drug design, diagnosis of disease and the environment. Chemists usually synthesise these molecules in the laboratory. We will use an innovative new approach to producing molecules that interact with DNA, that as fast and efficient and mirrors the processes used by Nature to make natural products. This research may lead to the design of new ....Targeting DNA with Dynamic Combinatorial Chemistry. The interaction of molecules with DNA, the molecule that controls genetic information, is fundamental to drug design, diagnosis of disease and the environment. Chemists usually synthesise these molecules in the laboratory. We will use an innovative new approach to producing molecules that interact with DNA, that as fast and efficient and mirrors the processes used by Nature to make natural products. This research may lead to the design of new therapeutics, diagnostics and applications that will benefit the Australian community, and will provide excellent training of researchers in skills required for employment in the biotechnology and pharmaceutical fields.Read moreRead less
Structure-activity relationships in the development of new bioactive isoflavonoids. This project aims to develop new chemical substances based on the structure of a group of naturally occuring compounds called isoflavones. Biological activity related to chronic inflammatory (eg arthritis) and heart disease will be examined in cells and animal models. This information will be used to design compounds with enhanced activity. The eventual aim is to develop potential therapeutic agents to treat chr ....Structure-activity relationships in the development of new bioactive isoflavonoids. This project aims to develop new chemical substances based on the structure of a group of naturally occuring compounds called isoflavones. Biological activity related to chronic inflammatory (eg arthritis) and heart disease will be examined in cells and animal models. This information will be used to design compounds with enhanced activity. The eventual aim is to develop potential therapeutic agents to treat chronic inflammatory and cardiovascular disease.Read moreRead less
Synthesis of the pyrrolo[2,1-c][1,4]benzodiazepines: potent DNA binders. Chemicals that bind to DNA have a long history of use as anticancer drugs. In recent times, the biotechnology revolution has greatly expanded our understanding of how these drugs work and the genetic basis of a wide range of other diseases. The aim of this project is to discover novel compounds that selectively bind to DNA. Starting from a class of naturally occurring compounds (called the pyrrolobenzodiazepines) as a templ ....Synthesis of the pyrrolo[2,1-c][1,4]benzodiazepines: potent DNA binders. Chemicals that bind to DNA have a long history of use as anticancer drugs. In recent times, the biotechnology revolution has greatly expanded our understanding of how these drugs work and the genetic basis of a wide range of other diseases. The aim of this project is to discover novel compounds that selectively bind to DNA. Starting from a class of naturally occurring compounds (called the pyrrolobenzodiazepines) as a template, it will develop powerful new methods to supply wholly new DNA interactive molecules with great potential as new drugs to treat cancer or other genetic diseases.Read moreRead less
Anti-Cancer Natural Products: Total Synthesis and Biological Evaluation of Lasonolide A and Analogues. One in three men and one in four women in Australia will be diagnosed with cancer before they reach 75. Cancer is a leading cause of death within this country with 28% of deaths each year due to this disease. Although there have been advances in the treatment of various forms of cancer there remains a pressing need for new therapies with improved potency, selectivity and reduced side effects. T ....Anti-Cancer Natural Products: Total Synthesis and Biological Evaluation of Lasonolide A and Analogues. One in three men and one in four women in Australia will be diagnosed with cancer before they reach 75. Cancer is a leading cause of death within this country with 28% of deaths each year due to this disease. Although there have been advances in the treatment of various forms of cancer there remains a pressing need for new therapies with improved potency, selectivity and reduced side effects. This project will provide new compounds of potential clinical use in the treatment of cancer, thereby aiding the large population of Australians who will be affected by this disease. Furthermore, the new advanced materials produced by this project will aid in the study of biochemical processes involved in cancer.Read moreRead less
High Pressure and Fluorous Approaches to Fostriecin Libraries: New Therapeutic Opportunities. The natural product, Fostriecin, displays considerable broad-spectrum anti-cancer activity, acting via a novel mechanism. However, this activity is tempered by its considerable instability, being too unstable to be used as a therapeutic agent. Using state-of-the-art approaches we will, rapidly generate libraries of more stable and biologically active fostriecin analogues and examine their potential to b ....High Pressure and Fluorous Approaches to Fostriecin Libraries: New Therapeutic Opportunities. The natural product, Fostriecin, displays considerable broad-spectrum anti-cancer activity, acting via a novel mechanism. However, this activity is tempered by its considerable instability, being too unstable to be used as a therapeutic agent. Using state-of-the-art approaches we will, rapidly generate libraries of more stable and biologically active fostriecin analogues and examine their potential to be used anti-cancer agents. This project represents an opportunity for Australia to take a significant, innovative lead in the development of hitherto unforseen therapeutic agents.Read moreRead less
Redox-Tuneable Sensitisers for Photodynamic Therapy of Malignant and Non-Malignant Proliferative Diseases. Cancer is currently Australia's leading cause of death with 85 231 new cases reported during 2000, costing the health system >$2 billion annually. Photodynamic Therapy is a promising anti-cancer therapy which combines the action of a photosensitising drug and light to destroy tumours. This project will lead to the development of new photosensitisers which will enable the specific targeting ....Redox-Tuneable Sensitisers for Photodynamic Therapy of Malignant and Non-Malignant Proliferative Diseases. Cancer is currently Australia's leading cause of death with 85 231 new cases reported during 2000, costing the health system >$2 billion annually. Photodynamic Therapy is a promising anti-cancer therapy which combines the action of a photosensitising drug and light to destroy tumours. This project will lead to the development of new photosensitisers which will enable the specific targeting of tumours while protecting healthy tissue from damage. Post-treatment skin photosensitivity will be minimised by antioxidant features integrated into the photosensitisers. The development of improved photosensitisers during this project will ultimately lead to improved treatment and new alternatives for Australian cancer sufferers.Read moreRead less
Anticancer Agents from Australian Marine Biodiversity. This project aims to initiate a proof of concept research collaboration in order to detect, isolate, characterise, identify and evaluate new marine anticancer drugs. This will be achieved through screening Australian marine biodiversity for the ability to inhibit key processes in tumor cell physiology. Significant outcomes from the project will not only be targets that yield new anticancer agents, but also the participation of Australian r ....Anticancer Agents from Australian Marine Biodiversity. This project aims to initiate a proof of concept research collaboration in order to detect, isolate, characterise, identify and evaluate new marine anticancer drugs. This will be achieved through screening Australian marine biodiversity for the ability to inhibit key processes in tumor cell physiology. Significant outcomes from the project will not only be targets that yield new anticancer agents, but also the participation of Australian researchers in the environmentally sustainable exploration, discovery and development of next generation anticancer drugs from Australia's unique marine biodiversity. Read moreRead less