Dissecting The Divisome: Development Of Antibacterial Agents That Inhibit Bacterial Cytokinesis
Funder
National Health and Medical Research Council
Funding Amount
$504,097.00
Summary
Infectious diseases accounted for 25-30% of the estimated 54 million deaths worldwide in 1998. Unfortunately, the recent spread of antibiotic resistant bacteria from hospitals into the community has coincided with a marked downturn in the rate of development of new antibiotics. Thus, there is an urgent need to develop new antimicrobial agents. The aim of this project is to provide essential groundwork for the development of new antimicrobials that inhibit bacterial cell division.
Probing Central And Peripheral Calcium Channel Sybtypes With Novel Omega Conotoxins
Funder
National Health and Medical Research Council
Funding Amount
$383,168.00
Summary
New toxins including omega-conotoxin CVID have been discovered from fish eating cone snails found on the Great Barrier Reef. These toxins discriminate between ion channel receptors on nerve cells that allow calcium ions to enter the cell and nerve transmission to continue. Of great importance is the fact that CVID specifically and potently blocks nerves that transmit pain responses. This project is involved with understanding the nolecular basis for this action with the goal of underpinning the ....New toxins including omega-conotoxin CVID have been discovered from fish eating cone snails found on the Great Barrier Reef. These toxins discriminate between ion channel receptors on nerve cells that allow calcium ions to enter the cell and nerve transmission to continue. Of great importance is the fact that CVID specifically and potently blocks nerves that transmit pain responses. This project is involved with understanding the nolecular basis for this action with the goal of underpinning the design of even more selective agents that will ameliorate pain while reducing side effects.Read moreRead less
Targeting Fungal Phospholipid Metabolism For Antifungal Drug Discovery
Funder
National Health and Medical Research Council
Funding Amount
$828,557.00
Summary
Invasive fungal infections are a serious and escalating health problem. They cause severe disease with a high death rate and are very costly to the health system. New antifungal drugs with novel properties are needed now because there are problems with current drugs. This project aims to develop potent new antifungal drugs that are effective in many fungal diseases and are well-tolerated.
Engineering Subtype Selective Inhibitors Of Voltage-sensitive Sodium Channels
Funder
National Health and Medical Research Council
Funding Amount
$406,980.00
Summary
During efforts to find new inhibitors of voltage sensitive sodium channels (VSSCs), we have discovered two new families of mu-conotoxins from Australian Conus tulipa and C. striatus that inhibit neuronal and muscle forms of the tetrodotoxin-sensitive (TTX-S) sodium channel. From these and related analogues we have identified a number of selective and highly potent inhibitors of VSSCs, opening the possibility of producing the first subtype selective TTX-S inhibitors useful in diseases such as epi ....During efforts to find new inhibitors of voltage sensitive sodium channels (VSSCs), we have discovered two new families of mu-conotoxins from Australian Conus tulipa and C. striatus that inhibit neuronal and muscle forms of the tetrodotoxin-sensitive (TTX-S) sodium channel. From these and related analogues we have identified a number of selective and highly potent inhibitors of VSSCs, opening the possibility of producing the first subtype selective TTX-S inhibitors useful in diseases such as epilepsy and stroke. These analogues also showed high selectivity for TTX-S sodium channels over a TTX-resistant (TTX-R) subtype hPN3, a key channel involved in the transmission of neuropathic pain that we recently cloned from human dorsal root ganglia. Given that TTX-S and TTX-R sodium channels have the same overall structure but differ at a relatively small number of key positions likely to affect mu-conotoxin binding, we believe it is possible to reverse engineer mu-conotoxin pharmacology in favour of the TTX-R form. This project will engineer subtype specific inhibitors of sodium channels in nerves through an understanding of how and wheremu-conotoxin bind to the sodium channel. Our long-term goal is to produce sodium channel drug candidates using m-conotoxins as templates for the development of subtype selective inhibitors of TTX-S and TTX-R sodium channels. The results of this study are designed to maximise the potential of this class of peptides as leads to the development of a new classes of therapeutics for pain, epilepsy and stroke.Read moreRead less
Selectivity And Mode Of Action Of Rho-conopeptide TIA: A Novel Inhibitor Of Alpha1-adrenoceptors.
Funder
National Health and Medical Research Council
Funding Amount
$399,300.00
Summary
A major obstacle to the development of safer and more effective treatments for cardivascular diseases and benign prostatic hyperplasia is the inability to find small molecules with sufficient specificity to be safe and effective. The applicant team brings together a unique set of complementary research interests and skills in using conotoxins to define, at the molecular level, how rho-conotoxins act at the alpha1-adrenoceptor, a major drug target for cardiovascualr and related diseases. Rho-cono ....A major obstacle to the development of safer and more effective treatments for cardivascular diseases and benign prostatic hyperplasia is the inability to find small molecules with sufficient specificity to be safe and effective. The applicant team brings together a unique set of complementary research interests and skills in using conotoxins to define, at the molecular level, how rho-conotoxins act at the alpha1-adrenoceptor, a major drug target for cardiovascualr and related diseases. Rho-conotoxins are novel peptide inhibitors of the alpha1-adrenoceptor that appear to act at an undescribed allosteric site. This Project will use rho-conotoxins and analogues to characterise structurally and functionally how and where this class of conopepides act. The structure activity relationship for rho-conotoxins will be established to guide the development of subtype specific inhibitors. Pairwise interactins between the alpha1-adrenoceptorand TIA will be used to dock TIA onto a homolgy model of the alpha1-adrenoceptor. The long-term goal of the project is to develop new and safer treatments for cardiovascular and related disorders.Read moreRead less