Determinants of Expression, Assembly and Function of the Noradrenaline Transporter. The noradrenaline transporter protein that is the focus of this project is important for mental health because it belongs to the family of proteins where psychostimulants, such as cocaine, and drugs used in the treatment of depression act. The project will lead to exciting advances in our understanding of how the structure of this protein controls its functions, and potentially to the design of better antidepress ....Determinants of Expression, Assembly and Function of the Noradrenaline Transporter. The noradrenaline transporter protein that is the focus of this project is important for mental health because it belongs to the family of proteins where psychostimulants, such as cocaine, and drugs used in the treatment of depression act. The project will lead to exciting advances in our understanding of how the structure of this protein controls its functions, and potentially to the design of better antidepressant drugs and to the design of drugs to prevent the effects of cocaine.Read moreRead less
Exploitation of a Novel Drug Target for Controlling Animal Trypanosomiasis. Trypanosomiasis greatly reduces livestock productivity in countries where it is endemic and is a threat to livestock and native wildlife in countries such as Australia where it is exotic but there is a risk of entry. New trypanocidal drugs with different modes of action are urgently needed to overcome growing resistance. This project aims to characterise trypanosome tubulin and, with this information, produce new tubulin ....Exploitation of a Novel Drug Target for Controlling Animal Trypanosomiasis. Trypanosomiasis greatly reduces livestock productivity in countries where it is endemic and is a threat to livestock and native wildlife in countries such as Australia where it is exotic but there is a risk of entry. New trypanocidal drugs with different modes of action are urgently needed to overcome growing resistance. This project aims to characterise trypanosome tubulin and, with this information, produce new tubulin-binding compounds for assessment in vitro and in vivo. Upon completion of the project it is expected that drug binding sites on trypanosome tubulin will be characterised and at least one candidate for clinical trials identified.Read moreRead less
Evolutionary venomics: Venom system diversification in the animal kingdom. This proposal represents a tremendous opportunity for biodiscovery from the Australian toxic fauna. This will be achieved through the researcher's unique approach of investigating previously unmapped venom systems for divergent, bioactive proteins. An understanding of venomous animal protein evolution has practical implications for the treatment of envenomations - an enormous problem in Australia - as well as great pot ....Evolutionary venomics: Venom system diversification in the animal kingdom. This proposal represents a tremendous opportunity for biodiscovery from the Australian toxic fauna. This will be achieved through the researcher's unique approach of investigating previously unmapped venom systems for divergent, bioactive proteins. An understanding of venomous animal protein evolution has practical implications for the treatment of envenomations - an enormous problem in Australia - as well as great potential in drug discovery and other commercial applications. This project will provide Australian graduate and post-graduate students with finely tuned skills in cutting edge methodological techniques and a fluent understanding of molecular evolution, preparing them to be internationally competitive scientists.Read moreRead less
Novel insecticidal neurotoxins from Australian spider venoms. Insecticidal toxins have considerable potential as novel biopesticides to combat the evolution of widespread insect resistance to classical chemical pesticides. This problem is increasing both in Australia and internationally. This study aims to isolate and pharmacologically characterise potent and selective insecticidal neurotoxins from Australian arachnids. Our laboratories will isolate neurotoxins from spider venoms, determine thei ....Novel insecticidal neurotoxins from Australian spider venoms. Insecticidal toxins have considerable potential as novel biopesticides to combat the evolution of widespread insect resistance to classical chemical pesticides. This problem is increasing both in Australia and internationally. This study aims to isolate and pharmacologically characterise potent and selective insecticidal neurotoxins from Australian arachnids. Our laboratories will isolate neurotoxins from spider venoms, determine their selectivity in insect and mammal bioassays, determine their primary and tertiary structures, and investigate their structure-function relationships by electrophysiological techniques. These functional and structural data will allow the future engineering, by molecular or synthetic procedures, of viral biopesticide analogues with increased potency, stability and selectivity.Read moreRead less
New drugs for malaria that target histone deacetylases. There is no vaccine for malaria and current drugs are failing, contributing to millions of malaria-related deaths each year. The aim of this project is to develop new drugs to address this significant global health issue. This project will focus on drugs that act in novel ways to existing malaria drugs by targeting enzymes that are involved in altering gene expression in the parasite. These kinds of enzymes are recognised drug targets in ot ....New drugs for malaria that target histone deacetylases. There is no vaccine for malaria and current drugs are failing, contributing to millions of malaria-related deaths each year. The aim of this project is to develop new drugs to address this significant global health issue. This project will focus on drugs that act in novel ways to existing malaria drugs by targeting enzymes that are involved in altering gene expression in the parasite. These kinds of enzymes are recognised drug targets in other diseases such as cancer. The outcomes of this project will include advances in malaria drug development that build on Australian drug discovery efforts, seeding further funding opportunities from industry and other sources and contributing research training and capacity building in Australia.Read moreRead less
Molecular evolution and toxinology of colubrid snake venom toxins. This project proposes to examine the origin and evolution of venom systems in advanced snakes (Caenophidia) focusing on the colubrid radiation comprising the rear-fanged species. Demonstration by us of the presence of a potent postsynaptic neurotoxin in the Durvenoy's secretions of the Asian ratsnake Elaphe radiata, an archetypal non-venomous colubrid species, forced a fundamental rethink of venom evolution. The toxin is homologo ....Molecular evolution and toxinology of colubrid snake venom toxins. This project proposes to examine the origin and evolution of venom systems in advanced snakes (Caenophidia) focusing on the colubrid radiation comprising the rear-fanged species. Demonstration by us of the presence of a potent postsynaptic neurotoxin in the Durvenoy's secretions of the Asian ratsnake Elaphe radiata, an archetypal non-venomous colubrid species, forced a fundamental rethink of venom evolution. The toxin is homologous with the three finger toxins, previously thought unique to elapids, and supports the role of venom as a key evolutionary innovation in the diversification of advanced snakes. This project extends this work to other species and toxin families.Read moreRead less
Characterisation of two-pore domain potassium channels: structure-function studies of the M1-P1 loops of TASK channels. TWIK-related Acid Sensitive K+ (TASK) channels are members of the novel class of two-pore domain potassium channel family. They are potently inhibited by local anaesthetics and have been implicated as having important roles in many pathophysiological conditions such as heart arrythmias, stroke, epilepsy, breast and other cancers. The in depth structural and functional character ....Characterisation of two-pore domain potassium channels: structure-function studies of the M1-P1 loops of TASK channels. TWIK-related Acid Sensitive K+ (TASK) channels are members of the novel class of two-pore domain potassium channel family. They are potently inhibited by local anaesthetics and have been implicated as having important roles in many pathophysiological conditions such as heart arrythmias, stroke, epilepsy, breast and other cancers. The in depth structural and functional characterisation of this class of potassium channels is of great importance as they are interesting targets for new therapeutic developments. Advancement of knowledge in the structure and function of these channels will underpin drug targeting that will aid preventative healthcare, allowing Australians to age well and age productively.Read moreRead less
Investigating the mechanisms of flavonoid actions on glycine receptors. The research to be conducted in this project will use state-of-the-art electrophysiological and molecular biological approaches to carefully characterise the actions of certain flavonoid compounds on the glycine-receptor channel. These compounds have recently been reported to act as modulators of ligand-gated ion channels, proteins integral to brain function and disease. However, no-one has studied in any detail the mechan ....Investigating the mechanisms of flavonoid actions on glycine receptors. The research to be conducted in this project will use state-of-the-art electrophysiological and molecular biological approaches to carefully characterise the actions of certain flavonoid compounds on the glycine-receptor channel. These compounds have recently been reported to act as modulators of ligand-gated ion channels, proteins integral to brain function and disease. However, no-one has studied in any detail the mechanisms by which these compounds act. By discovering their site and mechanisms of action we will further our understanding of these important proteins and their modulation, maintain Australia's significant expertise in this field and provide leads for future development of drugs with potential therapeutic value.Read moreRead less
Enhanced drug delivery using nanoparticulate dendrimer vectors. Many drug candidates fail during development because of low and variable absorption after oral administration. This project seeks to investigate the utility of specialised nanometer-sized macromolecules (dendrimers), to facilitate the improved delivery of drug molecules where low aqueous solubility is the principle limitation to drug absorption and will also be explored as vectors to specifically target drugs to intestinal lymphoid ....Enhanced drug delivery using nanoparticulate dendrimer vectors. Many drug candidates fail during development because of low and variable absorption after oral administration. This project seeks to investigate the utility of specialised nanometer-sized macromolecules (dendrimers), to facilitate the improved delivery of drug molecules where low aqueous solubility is the principle limitation to drug absorption and will also be explored as vectors to specifically target drugs to intestinal lymphoid (immune) tissue. This project will link the drug delivery expertise of Monash University with the experience in dendrimer design of the Australian biotechnology company Starpharma to provide concrete delivery solutions for the rapidly expanding biotechnology industry in Australia.Read moreRead less
Discovery Indigenous Researchers Development - Grant ID: DI0668388
Funder
Australian Research Council
Funding Amount
$87,458.00
Summary
The genetic basis for bioactivity in the traditional medicine plants of Australia. A plant species that produces a bioactive compound usually produce the compound in very small amounts. To allow for marketable levels of production of the bioactive compound, numerous amounts of plants would need to be removed from the environment. This not only removes the limited supply of possibly rare types of plants from the environment but also denies the use of this plant by traditional people. Locating and ....The genetic basis for bioactivity in the traditional medicine plants of Australia. A plant species that produces a bioactive compound usually produce the compound in very small amounts. To allow for marketable levels of production of the bioactive compound, numerous amounts of plants would need to be removed from the environment. This not only removes the limited supply of possibly rare types of plants from the environment but also denies the use of this plant by traditional people. Locating and using the genes responsible for producing these bioactive compounds will allow their sustainable biosynthesis.Read moreRead less