Engineered extrasynaptic GABAA receptors: Towards novel analgesics. Engineered extrasynaptic GABAA receptors: Towards novel analgesics. This project intends to alleviate neuropathic pain by developing drugs and good tool molecules targeting GABA-A receptors. About 20% of Australian adults suffer from neuropathic pain. Delta-containing GABA-A receptors represent attractive and novel targets for developing non-opioid analgesics. However, no drugs or good tool molecules target these receptors. This ....Engineered extrasynaptic GABAA receptors: Towards novel analgesics. Engineered extrasynaptic GABAA receptors: Towards novel analgesics. This project intends to alleviate neuropathic pain by developing drugs and good tool molecules targeting GABA-A receptors. About 20% of Australian adults suffer from neuropathic pain. Delta-containing GABA-A receptors represent attractive and novel targets for developing non-opioid analgesics. However, no drugs or good tool molecules target these receptors. This project intends to develop the needed enabling technologies, including screening assays, tool molecules and radioligands; and perform brain slice electrophysiology to confirm activity in neuronal cells. This project is expected to benefit the research community and future rational drug-discovery endeavours for drugs that modulate delta-containing receptors.Read moreRead less
Discovery and development of novel insulin sensitising compounds for the treatment of Type 2 diabetes. Diabetes is one of the major health problems facing Australia today, and current treatments are proving inadequate to combat this disease. We previously discovered a new drug with potential for development for the treatment of diabetes. In this project, we will identify how this drug works to combat diabetes in cell and animal models, and use novel chemistry approaches to modify the drug to imp ....Discovery and development of novel insulin sensitising compounds for the treatment of Type 2 diabetes. Diabetes is one of the major health problems facing Australia today, and current treatments are proving inadequate to combat this disease. We previously discovered a new drug with potential for development for the treatment of diabetes. In this project, we will identify how this drug works to combat diabetes in cell and animal models, and use novel chemistry approaches to modify the drug to improve its properties and reduce potential side-effects. The outcomes of this project will be understanding of a new biological process that contributes to the development of diabetes, and the discovery and characterisation of new chemical compounds that could be developed as drugs to treat diabetes.Read moreRead less
New approaches to inhibition of activity of HIV integrase. This project aims to assist in the development of novel anti-HIV drugs that will benefit the 17000 Australians and more than 33 million people worldwide who are currently suffering with this terrible disease. The project will utilise state-of-the-art approaches in structure-based drug design to identify and synthesise compounds as leads for the development of anti-HIV drugs. Furthermore, the project will provide invaluable training for t ....New approaches to inhibition of activity of HIV integrase. This project aims to assist in the development of novel anti-HIV drugs that will benefit the 17000 Australians and more than 33 million people worldwide who are currently suffering with this terrible disease. The project will utilise state-of-the-art approaches in structure-based drug design to identify and synthesise compounds as leads for the development of anti-HIV drugs. Furthermore, the project will provide invaluable training for the researchers involved and enhance the relationship between the academic and commercial collaborators.Read moreRead less
Structure-based design of inhibitors of HIV-1 integrase. This project will produce compounds that block human immunodeficiency virus (HIV) replication. These compounds will benefit the 17000 Australians and more than 34 million people worldwide who are currently suffering with this terrible disease.
Understanding the molecular basis of heparanase activity. This project aims to advance our understanding of the structure and impact on biological processes of heparanase (HSPE), an enzyme of critical importance. HSPE’s ability to interact with heparan sulfate (HS), a key component of the extracellular matrix and basement membranes, makes HPSE a pivotal enzyme in many important physiological and disease-related processes ranging from angiogenesis, tumour metastasis, inflammation, hair follicle ....Understanding the molecular basis of heparanase activity. This project aims to advance our understanding of the structure and impact on biological processes of heparanase (HSPE), an enzyme of critical importance. HSPE’s ability to interact with heparan sulfate (HS), a key component of the extracellular matrix and basement membranes, makes HPSE a pivotal enzyme in many important physiological and disease-related processes ranging from angiogenesis, tumour metastasis, inflammation, hair follicle development to wrinkle formation. The knowledge gained through this project is expected to provide new insight into the interaction between HSPE and HS/HSPG to reveal new pathways to the development of inhibitors to treat diseases such as cancer and diabetes.Read moreRead less
Novel chemoenzymatic synthesis and bioconjugation of peptides and proteins. This project aims to solve the critical difficulty of producing the complex peptide insulin and related insulin-like peptides (INSLs) and their analogues. The project will use unique, recyclable enzymes which ligate smaller peptide segments with extraordinary site and substrate selectivity. The expected outcome of the project is novel, cheaper and scalable, enzyme-mediated engineering of this critical class of peptides a ....Novel chemoenzymatic synthesis and bioconjugation of peptides and proteins. This project aims to solve the critical difficulty of producing the complex peptide insulin and related insulin-like peptides (INSLs) and their analogues. The project will use unique, recyclable enzymes which ligate smaller peptide segments with extraordinary site and substrate selectivity. The expected outcome of the project is novel, cheaper and scalable, enzyme-mediated engineering of this critical class of peptides as biological probes and potential therapeutic agents.Read moreRead less
Applying the CCK framework to angiogenic-based therapeutics. The aim of this project is to graft peptides involved in angiogenesis-related disorders onto a mini-protein framework. The cyclic cystine knot (CCK) framework is a plant based protein framework that has unique structural properties that make it exceptionally stable. The significance of this project is that the framework has the potential to overcome the limitations that are generally associated with peptide-based therapeutics, includin ....Applying the CCK framework to angiogenic-based therapeutics. The aim of this project is to graft peptides involved in angiogenesis-related disorders onto a mini-protein framework. The cyclic cystine knot (CCK) framework is a plant based protein framework that has unique structural properties that make it exceptionally stable. The significance of this project is that the framework has the potential to overcome the limitations that are generally associated with peptide-based therapeutics, including poor stability and bioavailability. Vastly improved therapeutic leads may be produced from this approach.Read moreRead less
What is in therapeutically prescribed herbal medicines? Phytochemical characterisation of steroidal saponins from two popular nutraceuticals, False Unicorn and Tribulus terrestris. Plants containing steroidal saponins have long been used as therapeutic products, but their active constituents remain poorly characterized. This project aims to identify and structurally characterize steroidal saponins from False Unicorn and Tribulus terrestris, two popular nutraceuticals which are currently marketed ....What is in therapeutically prescribed herbal medicines? Phytochemical characterisation of steroidal saponins from two popular nutraceuticals, False Unicorn and Tribulus terrestris. Plants containing steroidal saponins have long been used as therapeutic products, but their active constituents remain poorly characterized. This project aims to identify and structurally characterize steroidal saponins from False Unicorn and Tribulus terrestris, two popular nutraceuticals which are currently marketed in Australia. Existing knowledge of these saponin constituents is surprisingly incomplete and inaccurate. Full structural elucidation will enable the development of 'standardised' herbal saponin profiles for better control of product quality and will allow alternatives for the herbs to be chosen, which cannot be undertaken until this composition is known. A phytochemical survey of Australian Tribulus terrestris will determine whether this native sub-species is suitable for commercial harvest.Read moreRead less
Subtype selectivity and functional bias of receptor positive allosteric modulators for understanding models of pulmonary disease. G-protein-coupled receptors (GPCRs) are an important superfamily of proteins that are involved in a myriad of physiological processes and a wide range of serious illnesses. This project seeks to gain a more detailed understanding of new mechanisms of GPCR modulation and function that will be of direct relevance to drug discovery.
Discovery and characterisation of novel spider-venom peptides targeting the human sodium ion channel Nav1.7. Drugs that selectively block the human sodium ion channel Nav1.7 are likely to be powerful analgesics for treating a wide variety of pain conditions. However, it has proved difficult to obtain selective blockers of this channel. The aim of this project is to determine whether spider-venoms might provide a source of highly selective Nav1.7 blockers.