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.
Modulation Of Feeding Through Pharmacological Targeting Of The Relaxin-3 Receptor RXFP3
Funder
National Health and Medical Research Council
Funding Amount
$584,955.00
Summary
Relaxin-3 is a neuropeptide that regulates a number of physiological processes, including food intake, suggesting that the relaxin-3 receptor RXFP3 may be a new target for treatment of eating disorders such as obesity. This project will develop new selective and high-affinity ligands for RXFP3, which will be critical pharmacological tools for the preclinical studies and evaluation of this system.
Gastrokine 2 Promotes Gastric Homeostasis And Inhibits Bacterial Pathology
Funder
National Health and Medical Research Council
Funding Amount
$621,335.00
Summary
Gastrokine 2 is a small regulatory protein secreted by the stomach lining. Its function is unknown but data from our lab suggests that it may be important in maintaining stomach integrity. This project will investigate how gastrokine 2 maintains stomach function, how this can be compromised when bacterial infection is ongoing, and how we might be able to turn up gastrokine 2 expression to prevent inflammation and precancerous changes in the stomach lining.
Development of Insulin-like peptide 5 (INSL5) peptide analogues as novel therapeutics. Insulin-like peptide 5 (INSL5) is a naturally-occurring hormone in the body that likely plays a role in the control of appetite. This project aims to develop new molecules based on INSL5 that could be suitable for use as drugs to treat various appetite-related disorders, such as obesity (where patients eat too much) or anorexia (where patients eat too little).
Mechanisms Underlying APOBEC3G Restriction Of HIV-1
Funder
National Health and Medical Research Council
Funding Amount
$540,075.00
Summary
In the fight against worldwide HIV-AIDS, understanding natural cell defenses to the HIV virus may identify new virus targets and strategies to block HIV in humans. Here, we will use state-of-the-art, high resolution, fluorescent microscopy to understand how the recently identified cell protein, APOBEC3G, blocks the HIV life cycle in human cells. We anticipate that APOBEC3G will stop HIV from invading the nucleus of human cells to defend against HIV, a strategy we can apply to new therapies.
Envelope Glycoprotein Determinants Of HIV-1 Subtype C Tropism And Pathogenicity
Funder
National Health and Medical Research Council
Funding Amount
$657,745.00
Summary
HIV-1 subtype C is the most common subtype of HIV-w worldwide, yet we know comparatively little about how it causes disease in humans. This study will elucidate how HIV-1 subtype C evolves in patients to become more pathogenic over time.
Elucidating The Mechanisms And Consequences Of Clinical HIV-1 Resistance To The CCR5 Antagonist Maraviroc
Funder
National Health and Medical Research Council
Funding Amount
$622,732.00
Summary
CCR5 antagonists are a new class of anti-HIV drug, and maraviroc (MVC) is the only CCR5 antagonists that is licensed for use as a HIV treatment. Like all HIV treatments, drug resistance to MVC can develop in patients. This study will determine the mechanism of how HIV becomes resistant to MVC, which will permit the development of improved, second generation CCR5 antagonists, and will reveal ways to determine which patients are more likely to develop MVC resistance.
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.
Solid phase synthesis of side-chain cross-linked peptide oligomers. This research will provide a unique opportunity to investigate the biological pathways and causative factors leading to diseases such as Alzheimer’s disease. Such information will guide the design and development of therapeutic strategies and diagnostic reagents.