Fragment based screening to deliver drugs targeting tuberculosis and the gametocyte and liver stages of Plasmodium. This project will identify natural products that bind to critical proteins in malaria and tuberculosis to discover new ways to treat these diseases.
Novel peptide mimics for the disruption of chemical communication in bacteria. It is now well established that bacteria communicate with each other via small diffusible signalling molecules and coordinate their activities such as biofilm formation, swarming and expression of virulence factors in a coordinated manner. This project will investigate the synthesis of novel organic molecules that have the capacity to disrupt chemical communication in bacteria. This could allow control of the unwante ....Novel peptide mimics for the disruption of chemical communication in bacteria. It is now well established that bacteria communicate with each other via small diffusible signalling molecules and coordinate their activities such as biofilm formation, swarming and expression of virulence factors in a coordinated manner. This project will investigate the synthesis of novel organic molecules that have the capacity to disrupt chemical communication in bacteria. This could allow control of the unwanted microbial activity without the use of growth inhibitory agents such as antibiotics, preservatives and disinfectants that select for the resistant organisms. This elegant approach to eradicating the virulence behaviour of microbes represents a novel strategy to combat antimicrobial resistance.Read moreRead less
New scaffolds for antimicrobial discovery. This project aims to investigate the synthesis of novel glyoxylamide antimicrobial peptide mimics that have the capacity to disrupt bacterial membranes. The innovative interdisciplinary approach expects to generate new, small molecular antimicrobial mimics that possess a low propensity for developing resistance. This could allow control of the unwanted microbial activity without the use of antibiotics that select for the resistant organisms. It will pro ....New scaffolds for antimicrobial discovery. This project aims to investigate the synthesis of novel glyoxylamide antimicrobial peptide mimics that have the capacity to disrupt bacterial membranes. The innovative interdisciplinary approach expects to generate new, small molecular antimicrobial mimics that possess a low propensity for developing resistance. This could allow control of the unwanted microbial activity without the use of antibiotics that select for the resistant organisms. It will provide excellent training for young researchers and lead to high quality research publications in international journals.Read moreRead less
Investigations into the antibacterial mechanism of action of cannabidiol. This project aims to understand how the compound cannabidiol is able to kill bacteria by examining its interactions with bacteria from a genetic and molecular level. This research is critical, because future development of cannabidiol and design of improved analogs is predicated on knowing how it works. Expected outcomes include the first detailed understanding of how cannabidiol interacts with bacteria. This should lead ....Investigations into the antibacterial mechanism of action of cannabidiol. This project aims to understand how the compound cannabidiol is able to kill bacteria by examining its interactions with bacteria from a genetic and molecular level. This research is critical, because future development of cannabidiol and design of improved analogs is predicated on knowing how it works. Expected outcomes include the first detailed understanding of how cannabidiol interacts with bacteria. This should lead to significant benefits, including high impact publications, additional collaborations with industrial partner Botanix, and a new class of antibiotics to overcome antibiotic resistance.Read moreRead less
Developing new tools for chemical biology. We will develop new synthetic strategies to support the development of small molecule chemical probes that bind with high affinity and specificity to a target protein. Such chemical probes are invaluable in elucidating the role of specific proteins in biological pathways. Our novel strategy aims to be rapid, efficient in its use of materials and widely applicable to a range of different protein targets. The core of our approach involves using biophysica ....Developing new tools for chemical biology. We will develop new synthetic strategies to support the development of small molecule chemical probes that bind with high affinity and specificity to a target protein. Such chemical probes are invaluable in elucidating the role of specific proteins in biological pathways. Our novel strategy aims to be rapid, efficient in its use of materials and widely applicable to a range of different protein targets. The core of our approach involves using biophysical binding assays to characterise compounds that are produced on small scale using parallel chemistry. This approach will enable better chemical probes to be developed more rapidly at lower cost than is currently possible.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE120100071
Funder
Australian Research Council
Funding Amount
$290,000.00
Summary
Chemi–biology computational platform for lead discovery in infectious disease. A challenge in fighting infectious disease is in finding new bioactive compounds. This facility will provide a high performance computational environment designed to accelerate the discovery of quality compounds for use in anti-infective medicine.
Interrogating diarylquinoline toxicity with targeted organic synthesis. Bedaquiline is the only new first-line treatment with a new mechanism of action to treat TB in the last 40 years, approved by the FDA on 31 December 2012. Alarmingly, this compound, has significant toxicities. The hypothesis tested in this project is that decreasing lipophilicity and basicity in this class of compounds while retaining target affinity will decrease toxicity but retain anti-TB activity. The project aims to: sy ....Interrogating diarylquinoline toxicity with targeted organic synthesis. Bedaquiline is the only new first-line treatment with a new mechanism of action to treat TB in the last 40 years, approved by the FDA on 31 December 2012. Alarmingly, this compound, has significant toxicities. The hypothesis tested in this project is that decreasing lipophilicity and basicity in this class of compounds while retaining target affinity will decrease toxicity but retain anti-TB activity. The project aims to: synthesise novel heteroarylalkylamines distinct from bedaquiline and designed to be more polar, less basic, and metabolically more stable; and, test all successfully synthesised target compounds for mechanism-based anti-tuberculosis activity, hERG-mediated cardiotoxicity, metabolic instability, and phospholipidosis.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE100100226
Funder
Australian Research Council
Funding Amount
$424,000.00
Summary
Advanced molecular discovery and characterisation facility. Natural product drug discovery in Australia requires access to high throughput functional assays to guide the separation and of novel bioactives with therapeutic potential. By establishing the advanced molecular discovery and characterisation facility in an academic environment across two institutions, research programs in early drug lead discovery and characterisation will be accelerated. It will provide unique capabilities not curren ....Advanced molecular discovery and characterisation facility. Natural product drug discovery in Australia requires access to high throughput functional assays to guide the separation and of novel bioactives with therapeutic potential. By establishing the advanced molecular discovery and characterisation facility in an academic environment across two institutions, research programs in early drug lead discovery and characterisation will be accelerated. It will provide unique capabilities not currently available in Australia, and help Australian researchers remain internationally competitive in breakthrough science and frontier technologies. The research enabled by this facility will lead to development of new drug candidates by the emerging Australian biotechnology industry.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE100100010
Funder
Australian Research Council
Funding Amount
$720,000.00
Summary
A 5-D Correlative Imaging Platform: Combining the strengths of light and electron microscopy. This will be Australia's first dedicated five-dimensional multiphoton-microscopy platform, allowing observation of dynamic structures across different length and time scales under controlled temperatures, followed by high-resolution electron microscopy studies on the same samples. This platform will provide a unique characterisation tool to Australia's top-flight investigators, and so contribute to the ....A 5-D Correlative Imaging Platform: Combining the strengths of light and electron microscopy. This will be Australia's first dedicated five-dimensional multiphoton-microscopy platform, allowing observation of dynamic structures across different length and time scales under controlled temperatures, followed by high-resolution electron microscopy studies on the same samples. This platform will provide a unique characterisation tool to Australia's top-flight investigators, and so contribute to the nation's research priorities. It will enable: fundamental studies of cancer, neural diseases and immune disorders; the development of frontier technologies, such as smart nanomaterials, biosensors and targeted drug delivery; and applied research to help plants and soils adapt to climate variability, and to increase sustainable use of water.Read moreRead less