Development Fo A Novel Treatment For Asthma: The Identification Of Lead Small Molecule Antagonists Of The IL-13/IL-13 Re
Funder
National Health and Medical Research Council
Funding Amount
$99,750.00
Summary
In developed countries Asthma ranks among the most common chronic illnesses. Over two million Australians now have this condition and the cost to our community is estimated to be in excess of $720 million per annum. In 1996 researchers at The Walter and Eliza Hall Institute discovered a new member of the cytokine receptor family, IL-13Ra1, which further research has strongly implicated in the pathology of this disease. The main goal of the proposed research is to discover small molecule antagoni ....In developed countries Asthma ranks among the most common chronic illnesses. Over two million Australians now have this condition and the cost to our community is estimated to be in excess of $720 million per annum. In 1996 researchers at The Walter and Eliza Hall Institute discovered a new member of the cytokine receptor family, IL-13Ra1, which further research has strongly implicated in the pathology of this disease. The main goal of the proposed research is to discover small molecule antagonists of IL-13Ra1 and to identify those suitable for development as novel asthma therapeutics.Read moreRead less
Macrophage Polarisation And Control Of Pulmonary Inflammation.
Funder
National Health and Medical Research Council
Funding Amount
$895,494.00
Summary
As key immune cells, macrophages are polarised to phenotypes that turn inflammation on or off. In cystic fibrosis, defective macrophage polarisation enhances inflammation and prevents lung repair. We are defining the molecules and cellular pathways that control this process and identifying targets for existing drugs that can be used to reprogram macrophages and restore lung repair to improve patient outcomes.
Epilepsy is one of the most common chronic neurological disorders; it affects 1% of the world’s population, yet about 1 in 3 patients fail to achieve seizure control with current drugs. We will improve the properties of small molecules (drugs) that specifically target the GTPase activity of the enzyme dynamin, to reduce seizure effect in the brain by a novel mechanism. We will optimize and pre-clinically test these future chemical entities as potential anti-epileptic drugs.
Unconventional Mechanisms For Activating The NLRP3 Inflammasome
Funder
National Health and Medical Research Council
Funding Amount
$747,031.00
Summary
Many inflammatory driven diseases such as arthritis, atherosclerosis and septic shock are also associated with cell death. This project will identify, at the molecular level, how cell death signalling specifically acts to trigger pathological inflammation. As such, it will identify novel targets for the development of next generation anti-inflammatory drugs.
Structure-based Design Of Novel Therapeutics For Multi-drug Resistant Neisseria Gonorrhoeae
Funder
National Health and Medical Research Council
Funding Amount
$669,148.00
Summary
Multiple drug resistance (MDR) in bacteria represents one of the most intractable problems facing modern medicine. The recent superbug, MDR-Neisseria gonorrhoeae (MDR-Ng), causes the sexually transmitted infection gonorrhoeae. A multi disciplinary team with expertise in structural biology, medicinal chemistry and bacteriology will establish a comprehensive knowledge base aimed at developing new antibiotics to treat MDR-Ng by targeting a bacterial protein virulence factor.
Development Of Small Molecule Modulators Of Apoptosis
Funder
National Health and Medical Research Council
Funding Amount
$621,558.00
Summary
Cancers rely on the deregulation of key cellular pathways. Along with biological and genetic tools, small molecules are powerful probes to understand these mechanisms. During the course of this research program, we will develop new and drug-like molecules that reinstate the cell death process to combat malignancies. This research will bring important advances for potential chemotherapies and create probes to better understand the biology of programmed cell death processes.
Developing Novel Anti-cancer Agens By High Throughput Chemical Screens For Small Molcules That Modulate The Pro-survival
Funder
National Health and Medical Research Council
Funding Amount
$125,000.00
Summary
Cancer is the second commonest cause of deaths in our community. Unfortunately, treatment often fails or causes unwanted side effects. This proposal seeks to discover and develop a novel class of anti-cancer drugs that act by directly activating programmed cell death (apoptosis). The Bcl-2 proteins are key regulators of cell death and by exploiting knowledge about these prime targets for cancer therapy, we aim to discover drugs that are potentially of considerable medical and commercial value.
Unraveling Fibrosis By Pharmacological Targeting Of The G Protein-coupled Receptor, RXFP1
Funder
National Health and Medical Research Council
Funding Amount
$798,618.00
Summary
Peptides, with their high specificity and low toxicity profiles, are highly attractive alternatives to small molecule drugs. H2 relaxin, a peptide hormone, has a strong potential for treating fibrosis. However, the large size of H2 relaxin makes it difficult and expensive to manufacture. Once administered to patients, it is also quickly degraded. We have developed a small anti-fibrotic relaxin peptide, and propose to understand its mechanism of action and improve its therapeutic indices.
Targeting Cytokine Signalling In Systemic Lupus Erythematosus
Funder
National Health and Medical Research Council
Funding Amount
$917,626.00
Summary
Systemic lupus erythematosus is a disease where the immune system attacks normally healthy tissues. The spontaneous overproduction of signalling molecules called interferons in lupus plays an important role in the severity of the disease. We have found that two proteins, named Bcl6 and PLZF, are important in controlling the interferon response in lupus patients. We propose that identifying how these proteins act to control interferon will aid in developing new treatments for lupus.