Plant peptides as modulators of invertebrate neurohormone receptors. Naturally-occurring peptides are widely distributed in many plants, but their biological role is often unclear. Circular plant peptides (called cyclotides) that share similarities with the neuropeptide oxytocin, and acts on its receptor, have been previously isolated. This signalling system is important for reproduction, development, and behaviour as well as water homeostasis. To elucidate the natural function of cyclotides. Th ....Plant peptides as modulators of invertebrate neurohormone receptors. Naturally-occurring peptides are widely distributed in many plants, but their biological role is often unclear. Circular plant peptides (called cyclotides) that share similarities with the neuropeptide oxytocin, and acts on its receptor, have been previously isolated. This signalling system is important for reproduction, development, and behaviour as well as water homeostasis. To elucidate the natural function of cyclotides. This project aims to characterise the pharmacological properties and biological effects of invertebrate receptors and their modulation by cyclotides. The notion that plants produce molecules to target invertebrate receptors is extremely appealing and will enhance knowledge about fundamental biological processes of plant-animal ecology.Read moreRead less
Structure and function of predatory and defensive venoms in cone snails. This project aims to investigate newly-discovered cone snail venoms to accelerate the search for novel bioactive peptides. It was recently discovered that cone snails can rapidly and reversibly switch between distinct venoms in response to predatory or defensive stimuli, implying that defensive and predatory venoms have evolved under separate selection pressures. The project plans to obtain separate predatory and defensive ....Structure and function of predatory and defensive venoms in cone snails. This project aims to investigate newly-discovered cone snail venoms to accelerate the search for novel bioactive peptides. It was recently discovered that cone snails can rapidly and reversibly switch between distinct venoms in response to predatory or defensive stimuli, implying that defensive and predatory venoms have evolved under separate selection pressures. The project plans to obtain separate predatory and defensive venoms and venom duct tissue from individual cone snails to compare and contrast the structure and function of conotoxins evolved for predation versus those evolved for defence, to elucidate the structure and function of these important classes of bioactive peptides.Read moreRead less
Synthetic Endonucleases: Novel DNA Cleaving Agents for Cancer Chemotherapy. Cancer is a common disease in our society, with more than 1 in 4 of us dieing from it. The current survival rate is 50%, and has been so for the past 5 decades. Thus, there is clearly an urgent need for better forms of therapy. Chemotherapy is the mainstay of treatment once the disease has spread from its original site. The National Benefits from the development of a new class of effective cancer drug are two-fold. Firs ....Synthetic Endonucleases: Novel DNA Cleaving Agents for Cancer Chemotherapy. Cancer is a common disease in our society, with more than 1 in 4 of us dieing from it. The current survival rate is 50%, and has been so for the past 5 decades. Thus, there is clearly an urgent need for better forms of therapy. Chemotherapy is the mainstay of treatment once the disease has spread from its original site. The National Benefits from the development of a new class of effective cancer drug are two-fold. Firstly, much relief will come to people suffering from cancer, as some will live longer, and some will be cured. Secondly, the economic benefits are extensive, since the world market in cancer drugs is measured in billions $US, and significant monies will flow to those who hold the intellectual property rights. Read moreRead less
Allosteric modulators as novel probes of G-Protein coupled receptor function. This research will provide novel mechanistic understanding on the function of one of the largest protein families in the mammalian genome, and the most important family with respect to drug targets. The insights gained thus have direct relevance to drug discovery. The discovery of novel G protein-coupled receptor (GPCR) allosteric enhancers will not only lead to potentially new therapeutic agents, but can significant ....Allosteric modulators as novel probes of G-Protein coupled receptor function. This research will provide novel mechanistic understanding on the function of one of the largest protein families in the mammalian genome, and the most important family with respect to drug targets. The insights gained thus have direct relevance to drug discovery. The discovery of novel G protein-coupled receptor (GPCR) allosteric enhancers will not only lead to potentially new therapeutic agents, but can significantly value-add to other national research efforts focusing on GPCR structural biology.Read moreRead less
Understanding allosteric modulation and functional selectivity at G Protein-Coupled Receptors (GPCRs). 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.
The Design and Development of the Next Generation Anti-HIV Drugs. This medicinal chemistry project will develop new computer-aided modelling techniques for drug design and development and will then apply them to the design of new therapeutics for the treatment of HIV-1/AIDS. Once developed, these new techniques can also be applied to other disease targets including various cancers, where specific proteins have been identified as causative. This research will also contribute to the education of y ....The Design and Development of the Next Generation Anti-HIV Drugs. This medicinal chemistry project will develop new computer-aided modelling techniques for drug design and development and will then apply them to the design of new therapeutics for the treatment of HIV-1/AIDS. Once developed, these new techniques can also be applied to other disease targets including various cancers, where specific proteins have been identified as causative. This research will also contribute to the education of young scientists, training them in cutting-edge research skills.Read moreRead less
Molecular probe development for high specificity and spatiotemporal control. This project aims at developing next-generation molecular probes with enhanced specificity and spatiotemporal control for the study of proteins and neuropeptide signalling. It addresses recognised knowledge gaps and technical bottlenecks in neuropeptide and memory research. Expected outcomes include a deeper molecular understanding of long-term memory formation and the role of neuropeptides in this process, as well as i ....Molecular probe development for high specificity and spatiotemporal control. This project aims at developing next-generation molecular probes with enhanced specificity and spatiotemporal control for the study of proteins and neuropeptide signalling. It addresses recognised knowledge gaps and technical bottlenecks in neuropeptide and memory research. Expected outcomes include a deeper molecular understanding of long-term memory formation and the role of neuropeptides in this process, as well as innovative chemistry strategies and novel molecular probes to advance fundamental research across the chemical and biological sciences. Anticipated benefits include technological innovations of relevance to Australia’s biotechnology sector and enhanced capacity for cross-disciplinary collaboration.Read moreRead less
The Design of New Integrase Inhibitors Targeting HIV-1. There is still no cure in sight for the worldwide HIV pandemic and the worsening viral resistance problem creates a need to find new and novel compounds for therapeutic use. This project aims to design and synthesize new anti-HIV drugs by targeting two separate enzymes within the HIV life-cycle. This 'dual-action' approach of designing a single molecular scaffold to target separate enzymes would enable a synergistic effect while minimizing ....The Design of New Integrase Inhibitors Targeting HIV-1. There is still no cure in sight for the worldwide HIV pandemic and the worsening viral resistance problem creates a need to find new and novel compounds for therapeutic use. This project aims to design and synthesize new anti-HIV drugs by targeting two separate enzymes within the HIV life-cycle. This 'dual-action' approach of designing a single molecular scaffold to target separate enzymes would enable a synergistic effect while minimizing development costs. The expected outcomes from this medicinal chemistry project include the discovery of new compounds with the potential for further development as therapeutic agents against HIV.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.