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DsbA Foldases From Multidrug Resistant Pathogens As Targets For New Antimicrobials
Funder
National Health and Medical Research Council
Funding Amount
$743,401.00
Summary
Bacteria that cause common human infections, such as cystitis and diarrhoea, are now resistant to many antibiotics. If no action is taken, by 2050 antibiotic resistant infections will kill more people each year than cancer. This project aims to address this global public health crisis by characterising promising new bacterial targets and inhibitors designed to disarm multidrug resistant pathogens. Longer term this work could provide new infection therapies that are urgently needed.
Dissecting The Pathogenic Triad Of Enteric Pathogens: Assembly, Structure And Function Of Autotransporter Proteases
Funder
National Health and Medical Research Council
Funding Amount
$639,428.00
Summary
SPATEs are proteases secreted by many enteric bacteria that contribute to their pathogenic potential by damaging host tissues and evading the host immune response. We aim to study the structural basis of their assembly and biological function. The information we gain will assist the development of new diagnostics and improved therapies for enteric infections.
Development Of Reversible Inhibitors Of Factor XIa
Funder
National Health and Medical Research Council
Funding Amount
$444,318.00
Summary
Blood usually clots in response to injury, but unwanted clots can cause thrombosis, as well as leading to stroke and heart disease. Existing drugs to treat thrombosis suffer from drawbacks such as invasive monitoring, interaction with diet and other medicines, and bleeding complications. New drugs are clearly needed. Our expert group of researchers will discover new anti-thrombotic compounds based upon our previous identification of natural products with anticoagulant properties.
Novel TB Drug Candidates Via The Inhibition Of Lipid I Biosynthesis
Funder
National Health and Medical Research Council
Funding Amount
$780,743.00
Summary
Tuberculosis (TB) is an enormous global health problem with a continuing impact in Australia. TB is now the leading killer of any infectious disease (1.8 million people per year) and the rapid emergence of drug resistant TB infections threatens to prevent efforts to control the disease. This project seeks to develop novel TB drug candidates that operate by preventing the construction of the cell wall by the bacterial agent that causes the disease.
Eradicating Leukaemic Stem Cells By Targeting The Arginine Methyltransferase PRMT5
Funder
National Health and Medical Research Council
Funding Amount
$770,950.00
Summary
Acute leukemia is a devastating cancer arising from primitive cells in the bone marrow called stem cells. We have identified a protein (PRMT5) that is highly expressed in leukemia stem cells. Our preliminary experiments suggest that blocking the function of this protein with a novel drug can stop the growth of these cells. This project will use a variety of mouse models of acute leukemia to determine how PRMT5 keeps stem cells alive and whether this drug will be a valuable new treatment.
An Integrated Approach To Combat Antibiotic Resistance
Funder
National Health and Medical Research Council
Funding Amount
$389,120.00
Summary
The development of antibiotics such as penicillin was hailed as one of the great breakthroughs in medicine. However, an increasing number of pathogens have acquired resistance to these drugs. One of the most common resistance mechanisms employed by these pathogens is the use of metal dependent enzymes that promote the degradation of antibiotics. To date, no clinically useful inhibitors for these enzymes are available. In this project, we aim to develop such inhibitors as therapeutic drug leads.
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.
Glutathione Transferase Omega 1 As A Novel Target For Sepsis And Other Inflammatory Disorders.
Funder
National Health and Medical Research Council
Funding Amount
$694,471.00
Summary
Sepsis is a major clinical problem that causes more deaths in Australia than breast, prostate or colon cancer. The deaths result from an overwhelming systemic inflammatory response to infection. We have discovered that this response is dependent on an enzyme called GSTO1-1 and that inhibitors can block the inflammatory response . In this study we will identify new drug like compounds that can inhibit GSTO1-1 and prevent death from sepsis.
Targeting Novel Sites On Reverse Transcriptase For HIV Treatment And Prevention
Funder
National Health and Medical Research Council
Funding Amount
$978,994.00
Summary
HIV/AIDS remains a major global threat with 37 million individuals living with HIV in 2014. Antiretroviral drugs have transformed HIV from a death sentence into a chronic disease. Public health organisations recommend dramatic scale up of drugs for HIV treatment and prevention. However, a major threat is that drug options will be exhausted due to drug resistance and toxicity. The major aim of this study is to undertake fundamental studies to advance the development of a new HIV drug class.
Structure-based Design Of Inhibitors Of PimA - A New Target For Tuberculosis Therapy
Funder
National Health and Medical Research Council
Funding Amount
$666,246.00
Summary
Tuberculosis (TB) is a devastating disease that kills 2 million people worldwide each year and affects one-third of the entire human population. Bacterial resistance to existing antibiotics is an ever increasing problem, highlighting the need to develop new anti-TB drugs. The aim of this project is to develop specific inhibitors to target a protein that is essential for the survival of the tuberculosis bacterium.