Structural Characterisation Of A Natural Inhibitor Of Sporulation Bound To Its Histidine Kinase Target
Funder
National Health and Medical Research Council
Funding Amount
$261,000.00
Summary
Many bacteria, including some which are virulent pathogens such as anthrax (Bacillus anthracis), are able to enter a dormant state by forming spores (sporulation). These spores are extremely robust and may persist in the environment buried in the soil for example for hundreds of years. The initiation of sporulation occurs in response to changes in the cellular and environmental conditions which threaten the free replicating existence of the bacterium. The process of sporulation is controlled at ....Many bacteria, including some which are virulent pathogens such as anthrax (Bacillus anthracis), are able to enter a dormant state by forming spores (sporulation). These spores are extremely robust and may persist in the environment buried in the soil for example for hundreds of years. The initiation of sporulation occurs in response to changes in the cellular and environmental conditions which threaten the free replicating existence of the bacterium. The process of sporulation is controlled at the molecular level by a complex signaling relay. It is of course vital for the existence of the organism that control of sporulation is tightly regulated - preventing the onset of spore-formation in any but the desired circumstances. We aim to determine the three-dimensional structures of the molecules involved in this regulated process and how, by interacting with each other, they can pass on the signal to the bacterium to either start or stop the spore forming process. Ultimately, the results of this work might lead to antibacterial agents which could be used to control particularly dangerous strains of bacteria.Read moreRead less
Investigating A Novel Generic Approach To Anti-Infective Agents
Funder
National Health and Medical Research Council
Funding Amount
$636,833.00
Summary
Alpha helical regions of proteins mediate infection by viruses and bacteria. Short peptides corresponding to these helical segments are unstructured in water. We will (a) test new technology for its generic capacity to stabilize 1-4 turns of alpha helical viral and bacterial peptides, (b) test small molecules for helical structure, and (c) test for antiviral, antibacterial or immunogenicity activity in cell assays. Proof of the technology may benefit many fields of medicine and health prevention ....Alpha helical regions of proteins mediate infection by viruses and bacteria. Short peptides corresponding to these helical segments are unstructured in water. We will (a) test new technology for its generic capacity to stabilize 1-4 turns of alpha helical viral and bacterial peptides, (b) test small molecules for helical structure, and (c) test for antiviral, antibacterial or immunogenicity activity in cell assays. Proof of the technology may benefit many fields of medicine and health prevention.Read moreRead less
Inhibition Of Siderophore Biosynthesis For Tuberculosis Drug Discovery
Funder
National Health and Medical Research Council
Funding Amount
$424,262.00
Summary
Tuberculosis (TB) is responsible for over 2 million deaths globally every year. Despite this alarming statistic, no new TB drugs have reached the market in 40 years. This is despite the emergence of strains of Mycobacterium tuberculosis (the causative agent of TB) that are resistant to currently prescribed drugs. This project aims to discover TB drug leads with a unique mode of action. This will be achieved by preparing compounds that prevent the bacterium from acquiring iron from the host.
This research draws together my expertise in medicinal chemistry, biochemistry, pharmacology and virology to design and develop new compounds that we can use to interrogate and regulate human and viral proteins that cause disease. Protein, cell and animal studies relevant to major 21st century health burdens (such as inflammatory, infectious and metabolic diseases, cancer, pain and viral infections) will provide important new information on mechanisms of disease development and drug action.
Maintaining fidelity in viral Ribonucleic acid (RNA) polymerases. This project will provide informed insights into the dynamics of viruses that currently impact a healthy start to life, ageing well and productively, and preventative healthcare. The analysis of viruses that cause gastroenteritis outbreaks will increase our understanding of how these viruses replicate and spread.
Exploring The Structure Activity Relationships Of Novel Trypsin Inhibitor SFTI-1 With Implications As Cancer Therapeutic
Funder
National Health and Medical Research Council
Funding Amount
$360,312.00
Summary
A novel peptide isolated from sunflower seeds has recently been shown to interact with an enzyme implicated in the growth of cancers and in particular prostate cancer. The proposed research involves developing this peptide as a therapeutic by performing a thorough analysis of the important features involved in its exciting anti-cancer activity.
Epigenetic Therapies As Molecular Probes To Investigate The Molecular Pathogenesis Of Leukaemia
Funder
National Health and Medical Research Council
Funding Amount
$937,402.00
Summary
A major limitation to the success of targeted therapies in cancer is the fact that we have few if any tools to study in detail their mechanism of action within cancerous and normal cells. If we were able to visualise these drugs within cells and precisely characterise the proteins, DNA and RNA within a cell that interact with these therapies we will be able to identify strategies that can optimise their efficacy and reduce the side-effects of these treatments.
Targeting Polymyxin-resistant Gram-negative Superbugs: Development Of Novel Antimicrobial Lipopeptides
Funder
National Health and Medical Research Council
Funding Amount
$661,069.00
Summary
Prevalence of resistance to antibiotics among Gram-negative 'superbugs' is a major global medical challenge, which is highlighted by the Bad Bugs, No Drugs campaign of the Infectious Diseases Society of America. There are virtually no new antibiotics in the current drug development pipeline for these dangerous pathogens. In this project, novel lipopeptides will be designed, synthesised and evaluated against these 'superbugs'. Information obtained will be crucial for further drug development.
Novel Therapeutic Strategy Against Multidrug-resistant Gram-negative Bacteria
Funder
National Health and Medical Research Council
Funding Amount
$349,823.00
Summary
In the past two decades, there has been a marked decline in discovery and development of new antibiotics while there has been a remarkable increase in resistance to the currently available antibiotics. The growth in the number of resistant bacteria and lack of antibiotics available for treatment is very significant with gram-negative bacteria, such as Pseudomonas aeruginosa, Acinetobacter baumannii and Stenotrophomonas maltophilia. Colistin, an old antibiotic that has been used little over the l ....In the past two decades, there has been a marked decline in discovery and development of new antibiotics while there has been a remarkable increase in resistance to the currently available antibiotics. The growth in the number of resistant bacteria and lack of antibiotics available for treatment is very significant with gram-negative bacteria, such as Pseudomonas aeruginosa, Acinetobacter baumannii and Stenotrophomonas maltophilia. Colistin, an old antibiotic that has been used little over the last 40-50 years, has been 'taken off the shelf' and is now being used as a last line of defence to treat people with infections caused by these bacteria. Clearly, doctors and their infected patients will be in an even more precarious position than currently exists if resistance to colistin increases. We have discovered a novel therapeutic strategy that is able to reverse colistin resistance in P. aeruginosa. The studies proposed in this project will investigate this novel strategy across a range of multidrug-resistant bacteria and provide the information essential for rational use in patients. We propose that such a novel therapeutic strategy will provide a powerful weapon for the war on these 'superbugs'.Read moreRead less