Malaria is a major global health problem. The protein AMA1 plays a key role in the invasion of host cells by malaria parasites, and agents that inhibit this interaction prevent host cell invasion and thus represent leads for the development of anti-malarial drugs. We have identified a number of chemical scaffolds that target a key site on AMA1. In this project we will optimize these leads to generate potent ligands for this site and evaluate the efficacy of these ligands as anti-malarial agents.
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.
Rapid method development in pharmaceutical analysis using quality-by-design principles. Chemical analysis using separation methods underpins all stages of drug design and analysis. This project will generate new approaches to greatly reduce the time taken to develop a new method of analysis. This will be achieved through development of new computerised techniques for rapid screening, selection and optimisation of analytical methods.
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.
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.
BioPPSy: An open source BIOchemical Property Prediction SYstem. Computer software will be developed for the prediction of the pharmacokinetic properties of small molecules to assist in the development of new compounds with drug-like properties. The software will be made freely available to promote its use and further development.
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
This study investigates how much an individual's genes and environment account for the wide variation in brain structure and function. Using brain imaging we examine in what way the connectivity of the brain of identical and non-identical twins is the same or different from that of their co-twin, and carry out analysis of their DNA to identify some of the genes involved. This will provide fundamental information on genetic mechanisms influencing variation in brain structure and function.