A Universal Prophylactic Vaccine For Hepatitis C Virus
Funder
National Health and Medical Research Council
Funding Amount
$643,337.00
Summary
Hepatitis C Virus (HCV) infects 200 million people world wide. An effective vaccine to prevent HCV is urgently needed but must afford protection against the 7 diverse genotypes. In this project grant we aim to further define the quality of the immune response that is generated by a novel HCV vaccine candidate that generates pan-genotypic immunity, its unique structural features, and methods of manufacturing so that it can be tested in a future phase I human clinical trial.
The Bcl-2 family of proteins is crucial for apoptosis (a form of programmed cell death) regulation. They target the mitochondrial outer membrane where they interact to determine cell fate. We will evaluate the membrane interactions of the Bcl-2 proteins in complementary biophysical and cellular experiments to redefine our understanding of the mechanism of apoptosis and provide new avenues for the development of compounds to selectively modulate diseases in which apoptosis is unregulated.
Development Of Selective Melanocortin Receptor Agonists And Antagonists
Funder
National Health and Medical Research Council
Funding Amount
$684,607.00
Summary
Human melanocortin receptors play a key role in a variety of physiological processes ranging from energy regulation, skin pigmentation and regulation of food intake. This project aims to generate novel peptide based molecules that will selectively interact with different melanocortin receptors to better understand their pharmacology thereby opening the potential for future drug development for obesity, stroke or inflammatory skin disorders.
Potent Small Molecule Modulators Of A Complement Protein In Inflammation
Funder
National Health and Medical Research Council
Funding Amount
$689,428.00
Summary
We have invented powerful new compounds that act on the cell surface and regulate inflammation. We plan to (1) fine-tune our small molecules for optimal activity on different kinds of immune cells; (2) understand mechanisms by which the compounds affect cellular inflammatory responses; (3) evaluate the compounds as potential treatments in rodent models of inflammatory diseases implicated from cell studies. This study is anticipated to lead to clinical studies for a new kind of drug treatment.
Determining Modes Of Binding And Activation Of Peptide G-protein Coupled Receptor Targets
Funder
National Health and Medical Research Council
Funding Amount
$576,538.00
Summary
The neuropeptide relaxin-3 and the peptide hormone INSL5 are recently discovered members of the relaxin peptide family. Relaxin-3 has important roles in stress and feeding whereas INSL5 is a gut hormone. We will study the interaction of relaxin-3 and INSL5 with their cell surface receptors and the mechanisms by which the receptors function. The knowledge gained will aid in the design of smaller, more potent and orally active forms of relaxin-3 and INSL5 for future clinical applications
Developing Functionalised Microbubbles For Molecular Ultrasound Imaging And Targeted Delivery Of Drugs And MicroRNA Therapeutics
Funder
National Health and Medical Research Council
Funding Amount
$677,229.00
Summary
We aim to develop gas-filled microbubbles that are directed to markers of thrombosis and inflammation and will allow visualisation of blood clots and early inflammatory reactions via ultrasound. This will allow early and timely treatment. We will systematically test for the best method of microbubble coating with recombinant antibodies in various animal models of thrombosis and inflammation. In addition, we plan to load microbubbles with drugs and target these to areas where they are needed.
Taking The First Steps From Promise To Product: Exploration Of The Newly Discovered Interleukin 37 Receptor Complex And Its Signaling Pathways
Funder
National Health and Medical Research Council
Funding Amount
$694,623.00
Summary
Cytokines are messenger proteins used by most cells of the body. They function as master regulators of many biological processes and as such play an important role in a wide spectrum of diseases. Anti-inflammatory cytokines attenuate the potentially destructive force of other cytokines and the immune system as a whole, and are therefore coveted as drug targets. We discovered the formidable anti-inflammatory properties of IL-37 and will now explore how these activites can be utilised in clinical ....Cytokines are messenger proteins used by most cells of the body. They function as master regulators of many biological processes and as such play an important role in a wide spectrum of diseases. Anti-inflammatory cytokines attenuate the potentially destructive force of other cytokines and the immune system as a whole, and are therefore coveted as drug targets. We discovered the formidable anti-inflammatory properties of IL-37 and will now explore how these activites can be utilised in clinical medicine.Read moreRead less
Signalling Through A Bioactive Aggrecan Fragment: What Is The Mechanism?
Funder
National Health and Medical Research Council
Funding Amount
$431,347.00
Summary
Osteoarthritis (OA) affects approximately 20% of Australians. There are no therapies that modify the course of the disease and joint replacement surgery is expensive and invasive. We have discovered that a peptide product of cartilage breakdown (the 32mer) signals cartilage cells to mount an inflammatory and catabolic response. We will determine how the 32mer triggers this response, whether other joint cells are similarly activated and how it can be stopped, with the goal of pursuing new targets ....Osteoarthritis (OA) affects approximately 20% of Australians. There are no therapies that modify the course of the disease and joint replacement surgery is expensive and invasive. We have discovered that a peptide product of cartilage breakdown (the 32mer) signals cartilage cells to mount an inflammatory and catabolic response. We will determine how the 32mer triggers this response, whether other joint cells are similarly activated and how it can be stopped, with the goal of pursuing new targets for therapyRead moreRead less
A Helminth-derived Peptide Is A Novel Prophylactic And Therapeutic Treatment For Autoimmune Disease
Funder
National Health and Medical Research Council
Funding Amount
$658,778.00
Summary
Parasitic worms (helminths) secrete molecules that possess a remarkable ability to skew the mammalian immune system towards anti-inflammatory responses. We have expoited a novel peptide secreted by helminths, which offers tremendous potential for the development of novel prophylactic and therapeutic treatments for a range of immune-mediated conditions. The overarching aim of this project is to further elucidate the mechanism of action and to determine the peptide’s clinical application.
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.