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
The basis of recognition and disposal of dysfunctional proteins by clusterin. When proteins become damaged they can precipitate. A blood protein called clusterin prevents precipitation of damaged proteins. Clusterin does this by forming complexes with the damaged proteins. Clusterin is the first blood protein known to do this. We will discover which parts of clusterin are responsible for this activity. We will also discover whether cells can take up and dispose of the complexes of clusterin and ....The basis of recognition and disposal of dysfunctional proteins by clusterin. When proteins become damaged they can precipitate. A blood protein called clusterin prevents precipitation of damaged proteins. Clusterin does this by forming complexes with the damaged proteins. Clusterin is the first blood protein known to do this. We will discover which parts of clusterin are responsible for this activity. We will also discover whether cells can take up and dispose of the complexes of clusterin and damaged proteins. This work is important because some diseases (eg, Alzheimers disease) involve the toxic effects of abnormal protein precipitation. Understanding how clusterin works may help in developing better treatments for these diseases.Read moreRead less
Novel Mass Spectrometric Approaches to the Study of Protein-Protein Interactions. Protein-protein interactions mediate all fundamental cellular processes, yet the structural complexity of protein assemblies mean they are often difficult to characterise using traditional analytical methods. This project will develop and demonstrate novel mass spectrometric approaches towards a molecular level description of the structure and interactions of biological protein complexes, which in turn may underpi ....Novel Mass Spectrometric Approaches to the Study of Protein-Protein Interactions. Protein-protein interactions mediate all fundamental cellular processes, yet the structural complexity of protein assemblies mean they are often difficult to characterise using traditional analytical methods. This project will develop and demonstrate novel mass spectrometric approaches towards a molecular level description of the structure and interactions of biological protein complexes, which in turn may underpin the rational design of drugs for the treatment of a range of human health conditions. This project will also provide training of young researchers to the highest international standards in mass spectrometry and protein science, for benefit to Australian industry and research.Read moreRead less
Nanosized peptide nucleic acid - metal complex hybrids as catalysts for the cleavage of phosphate ester bonds in biological molecules. The information from Human Genome Project is being used to generate molecules with a variety of therapeutic and diagnostic applications. The capability to design, synthesise and manipulate functional molecules that mimic biological processes will underpin many emerging applications. In this project, macrocyclic metal complexes that catalyse the cleavage of phosph ....Nanosized peptide nucleic acid - metal complex hybrids as catalysts for the cleavage of phosphate ester bonds in biological molecules. The information from Human Genome Project is being used to generate molecules with a variety of therapeutic and diagnostic applications. The capability to design, synthesise and manipulate functional molecules that mimic biological processes will underpin many emerging applications. In this project, macrocyclic metal complexes that catalyse the cleavage of phosphate ester bonds in biological molecules will be developed. Active complexes will be incorporated into nanosized peptide nucleic acid (PNA) - metal complex hybrids and applied as artificial enzymes in the sequence specific cleavage of RNA and DNA. Novel applications of these ?artificial enzymes? in biotechnology are anticipated.Read moreRead less
Negative ion mass spectrometry: fundamental studies and applied applications. We seek to:
(i) establish negative ion mass spectrometry as an analytical tool for the sequencing of proteins and to probe the structures of active peptide Ca2+ calmodulin complexes which, for example, inhibit the formation of NO from nitric oxide synthases. Controlling the concentration of nitric oxide may assist with the treatment of inflammatory and cardiac diseases, stroke and diseases of the central nervous syst ....Negative ion mass spectrometry: fundamental studies and applied applications. We seek to:
(i) establish negative ion mass spectrometry as an analytical tool for the sequencing of proteins and to probe the structures of active peptide Ca2+ calmodulin complexes which, for example, inhibit the formation of NO from nitric oxide synthases. Controlling the concentration of nitric oxide may assist with the treatment of inflammatory and cardiac diseases, stroke and diseases of the central nervous system.
(ii) to study the possibility of the formation of biological molecules of life in interstellar regions
(iii) to train graduate students to international standards in the chemistry of proteomics.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE0668534
Funder
Australian Research Council
Funding Amount
$770,000.00
Summary
High resolution bioanalytical Fourier transform mass spectrometer combined with liquid chromatograph. This project extends a network of advanced technology for bioanalysis that enables discoveries in biotechnology, molecular medicine and biochemistry. The proposed equipment includes the most powerful mass spectrometer (MS) currently available for bioanalysis to complement an existing network of instruments at four universities in Sydney. These include 3 of 4 nodes of the Australian Proteome Anal ....High resolution bioanalytical Fourier transform mass spectrometer combined with liquid chromatograph. This project extends a network of advanced technology for bioanalysis that enables discoveries in biotechnology, molecular medicine and biochemistry. The proposed equipment includes the most powerful mass spectrometer (MS) currently available for bioanalysis to complement an existing network of instruments at four universities in Sydney. These include 3 of 4 nodes of the Australian Proteome Analysis Facility (APAF). The new technology is a missing link in bioanalytical capability where other instruments are not sufficiently sensitive. The instrument will be managed by MS specialists at the Bioanalytical Mass Spectrometry Facility at UNSW (www.bmsf.unsw.edu.au) where access by and training of users is well established.Read moreRead less
Novel target of amiloride analogues - picornaviral RNA polymerase. Picornaviruses cause a range of diseases such as poliomyelitis, meningitis, myocarditis, hepatitis A, neonatal sepsis and common cold. No antiviral treatment is available for these infections. Nearly 50% of antiviral drugs used in medicine are viral polymerase inhibitors; however picornaviral RNA polymerase has been largely overlooked as a drug target. We have discovered a group of compounds that inhibit picornaviral RNA polymera ....Novel target of amiloride analogues - picornaviral RNA polymerase. Picornaviruses cause a range of diseases such as poliomyelitis, meningitis, myocarditis, hepatitis A, neonatal sepsis and common cold. No antiviral treatment is available for these infections. Nearly 50% of antiviral drugs used in medicine are viral polymerase inhibitors; however picornaviral RNA polymerase has been largely overlooked as a drug target. We have discovered a group of compounds that inhibit picornaviral RNA polymerase. This project aims to define the inhibition mechanism and to evaluate a potential use of these compounds for antiviral drug development.Read moreRead less
New analgesics based on µ-conotoxins: structure-based design of helical mimetics. Diseases in which voltage-gated sodium channels are implicated are contributors to morbidity and mortality in the Australian population, and this project promises to provide new leads for the future development of drugs to treat such diseases, in particular analgesics for the treatment of chronic pain. The generation of these leads will entail the development of new approaches to mimicking key regions of peptides a ....New analgesics based on µ-conotoxins: structure-based design of helical mimetics. Diseases in which voltage-gated sodium channels are implicated are contributors to morbidity and mortality in the Australian population, and this project promises to provide new leads for the future development of drugs to treat such diseases, in particular analgesics for the treatment of chronic pain. The generation of these leads will entail the development of new approaches to mimicking key regions of peptides and proteins in drug-like molecules. This is a highly interdisciplinary project, spanning structural biology, molecular design, medicinal chemistry, molecular biology and electrophysiology, and the training of PhD graduates with such broad experience represents another national benefit of the project.Read moreRead less
Drug targets in malaria parasites. Malaria is rampant throughout our Region and hinders the economies of our neighbours reducing regional prosperity and stability. Australian security and aid personnel deployed in the Region contract malaria infections and global warming could bring malaria-carrying mosquitoes south to Sydney. Australia is pre-eminent in malaria research, making lead discoveries in vaccine and drug development. However, we lack crucial resources to study the parasite in the mo ....Drug targets in malaria parasites. Malaria is rampant throughout our Region and hinders the economies of our neighbours reducing regional prosperity and stability. Australian security and aid personnel deployed in the Region contract malaria infections and global warming could bring malaria-carrying mosquitoes south to Sydney. Australia is pre-eminent in malaria research, making lead discoveries in vaccine and drug development. However, we lack crucial resources to study the parasite in the mosquito phase of its life cycle. The Federation Fellowship will create a malaria mosquito facility to redress this crucial gap in our capability. The Fellowship will double as foreign aid investment by enhancing our capacity to protect ourselves as well as supporting our neighbours.Read moreRead less
The role of intracellular calcium stores in cardiac pacemaking. The spontaneous firing of pacemaker cells is central to regulation of the cardiovascular system particularly during exercise. The discovery that pacemaker cell function is modulated in part by calcium ions will change our understanding of the changes in heart rate during exercise and in diseases which affect the pacemaker cells. Better understanding of the way in which spontaneous activity of these cells is regulated is the key to ....The role of intracellular calcium stores in cardiac pacemaking. The spontaneous firing of pacemaker cells is central to regulation of the cardiovascular system particularly during exercise. The discovery that pacemaker cell function is modulated in part by calcium ions will change our understanding of the changes in heart rate during exercise and in diseases which affect the pacemaker cells. Better understanding of the way in which spontaneous activity of these cells is regulated is the key to controlling or modifying their function.Read moreRead less