A Structural, Chemical And Functional Investigation Into MAIT Cell Receptor Recognition
Funder
National Health and Medical Research Council
Funding Amount
$1,196,304.00
Summary
This project is focused on a type of T-cell, termed a MAIT cell, which is found abundantly in the lining of the gut. We are investigating how this MAIT cell is activated by riboflavin and folic acid metabolites. We are also examining how commonly prescribed drugs impact MAIT cells and how such activation may be linked to diseases, including inflammatory bowel disease.
An Integrated Study Of Acyclic Nucleoside Phosphonates As Antimalarial Drugs
Funder
National Health and Medical Research Council
Funding Amount
$500,544.00
Summary
Malaria is one of the most serious infectious diseases today. Because of increasing resistance to existing medicines, new drugs are now needed. The therapeutic agents we will develop target the principal species responsible for human malaria are Plasmodium falciparum and vivax. Specifically, the compounds will prevent the parasite from replicating and are related in structure to those compounds in use to treat viral infections including AIDS.
Ketol-acid Reductoisomerase: An Important Antituberculosis Drug Target
Funder
National Health and Medical Research Council
Funding Amount
$690,113.00
Summary
Due to the increasing prevalence of drug resistance, new antituberculosis medications are urgently needed. Here, we will use rational structure-based approaches to design new inhibitors of ketolacid reductoisomerase (KARI), an enzyme whose activity is essential to the survival of this pathogen that resides in the lungs of humans. These inhibitors will be converted into prodrug formulations for optimal activity in cell-based assays and in mice infected with this pathogen.
Inhibitors Of Hypoxanthine-guanine-xanthine Phosphoribosyltransferase As Versatile Drugs To Treat Infectious Diseases
Funder
National Health and Medical Research Council
Funding Amount
$766,163.00
Summary
Due to the increase in resistance to many of the frontline drugs to treat bacterial and parasitic infections, there is an urgent need to develop new pipelines for drug discovery against the pathogens that are causative agents of this diseases. This project pioneers the blocking of nucleotide synthesis to develop new drug leads to treat malaria, human tuberculosis, African sleeping sickness, Chagas disease and uropathogenic E.coli infections.
Understanding Ligand Binding Within The Insulin-like Growth Factor Family With Direct Application To Cancer Therapeutic Design
Funder
National Health and Medical Research Council
Funding Amount
$861,235.00
Summary
Cancer is a devastating disease and there is an imperative to develop new therapeutics. The so-called insulin-like growth factors are molecules that play a key role in the initiation and progression of cancer. Here we seek to understand how these molecules interact with cells and to develop drugs that might block their action.
Targeting The Plasmodium Falciparum Metalloaminopeptidases For Development Of New Antimalarial Agents
Funder
National Health and Medical Research Council
Funding Amount
$565,507.00
Summary
Each year 1-2 million people will die from malaria. The prevention and treatment of malaria is becoming increasingly difficult due to the spread of drug-resistance. There is an urgent need for next generation of antimalarials with new modes of action. This project will develop new antimalarial agents against the malarial aminopeptidase drug targets.
Targeting Acetohydroxyacid Synthase To Discover New Antifungal Agents.
Funder
National Health and Medical Research Council
Funding Amount
$481,135.00
Summary
Invasive fungal infections are increasingly being recognized as a major life threatening risk to hospitalized patients. The efficacy of the current medications is sub-optimal due to the emergence of resistance and the high dosage regimes that are required to treat these infections. We propose to develop a new class of antifungal agent that target an enzyme, acetohydroxyacid synthase, whose activity is required for the survival of pathogenic fungi in mammals.
Structural Biology Of Bacterial Lipid II-glycopeptide Antibiotic Interactions
Funder
National Health and Medical Research Council
Funding Amount
$605,190.00
Summary
Drug resistant bacteria are threatening our ability to successfully treat serious life-endangering infections, with many common antibiotics no longer effective. We will study in atomic detail how one class of antibiotics interacts with bacteria in order to design new members of this group that can overcome resistance.
Artificial Synthesis Of The Type III Secretion System Translocon. A New Approach To Vaccine Design
Funder
National Health and Medical Research Council
Funding Amount
$668,742.00
Summary
Today hospitals are plagued with bacterial infections that do not respond to antibiotics. The problem exists because although antibiotics are effective at killing bacteria, this paradoxically also helps the drug-resistant bacteria thrive. We will pioneer a completely new approach to vaccine design that allows us to construct a vaccine that protects us from bacterial infection without killing the bacteria. The vaccine should therefore be far less susceptible to drug resistance.
Characterization And Inhibition Of Higher-order Assembly Signalling In Toll-like Receptor Pathways
Funder
National Health and Medical Research Council
Funding Amount
$711,995.00
Summary
The innate immune system is the first line of defence against pathogens. Inhibitors of innate immune pathways can be developed into therapeutic agents against a number of disorders including chronic inflammatory diseases, such as rheumatoid arthritis. We have discovered a new mechanisms of signaling by a set of key molecules in these pathways, through formation of large assemblies. We will characterize these assemblies and uncover ways to inhibit their formation.