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Developing Novel Peptide-based Therapeutics And Technologies To Mitigate Fibrosis
Funder
National Health and Medical Research Council
Funding Amount
$1,161,383.00
Summary
Fibrosis (tissue scarring) is an unmet medical problem that adversely affects both human health and medical devices. It causes organ (e.g. heart, kidney) failure leading to death. Fibrotic encapsulation causes medical device (e.g. surgical mesh) failure. Our team has discovered a peptide, B7-33, that mitigates fibrosis in the short-term. Our IDEAS grant aims to develop long-acting B7-33 therapies and, to employ long-acting B7-33 mimetics in anti-fibrotic compositions for surgical meshes.
Regulation Of Cellular Responses To Neuropeptides.
Funder
National Health and Medical Research Council
Funding Amount
$83,510.00
Summary
Neuropeptides are chemicals released from nerves that are responsible for communication between the nerves, glands, muscles or other nerves. Neuropeptides exert their diverse biological effects by interacting with small structures on the cells they wish to communicate with. These structures bind the neuropeptide and are termed neuropeptide receptors. The responses of tissues to neuropeptides, for example, contraction of muscle, decrease with continued exposure to the neuropeptide. This reduction ....Neuropeptides are chemicals released from nerves that are responsible for communication between the nerves, glands, muscles or other nerves. Neuropeptides exert their diverse biological effects by interacting with small structures on the cells they wish to communicate with. These structures bind the neuropeptide and are termed neuropeptide receptors. The responses of tissues to neuropeptides, for example, contraction of muscle, decrease with continued exposure to the neuropeptide. This reduction in response is termed desensitization is thought to turn off the response to cells following stimulation by neuropeptides. In this study, I will investigate the mechanisms behind the desensitization of VPAC receptors which are a found throughout the body and have many important roles for example, gastrointestinal, pancreatic and reproductive function and control of muscle. VPAC receptors are also highly expressed in certain many cancers such as breast, prostate and colon carcinoma. The wide variety of functions that these receptors perform and the wide distribution in the body suggest that these are very important receptors. To date research into the responses and desensitisation of these receptors has been lacking, and the work that has been done has become confusing as more receptors and neuropeptides which bind them are discovered. The current project aims to carefully study these receptors and to determine their role in health and disease. The understanding the interaction of receptor and neuropeptide can perhaps lead to development of new therapeutic agents.Read moreRead less
Understanding Cell Signalling Mechanisms Activated By Relaxin Family Peptides: Targets With Therapeutic Potential
Funder
National Health and Medical Research Council
Funding Amount
$306,842.00
Summary
One of the most powerful ways that the activity of the cells that make up the tissues and organs of the body can be changed is by the interaction of chemicals with proteins called receptors located at the cell surface. The commonest type of receptor is called a G-protein coupled receptor as it is linked to mechanisms inside the cell by the G-proteins. These receptors are the most commonly targeted by pharmaceutical companies that wish to alter the responses of cells for therapeutic purposes and ....One of the most powerful ways that the activity of the cells that make up the tissues and organs of the body can be changed is by the interaction of chemicals with proteins called receptors located at the cell surface. The commonest type of receptor is called a G-protein coupled receptor as it is linked to mechanisms inside the cell by the G-proteins. These receptors are the most commonly targeted by pharmaceutical companies that wish to alter the responses of cells for therapeutic purposes and almost 2-3 of all drugs currently marketed work through these proteins. This project will examine the mechanisms whereby certain types of G-protein coupled receptor produce signals in cells and determine what are the critical areas of the receptor for these interactions. The receptors involved have been discovered only in the last 4 years and little is known of the ways these change the activity of cells. The substances acting on these receptors have potential for development as targets for drugs that have the potential to treat fibrosis which is a feature of many diseases including cardiac failure, kidney failure and lung disease.Read moreRead less
Determinants Of Binding And Activity Of G-protein Coupled Receptors RXFP1 And RXFP2; The Receptors For Relaxin And INSL3
Funder
National Health and Medical Research Council
Funding Amount
$531,696.00
Summary
Relaxin is a hormone which has long been known to have essential roles in pregnancy and birth. However it has also been demonstrated to have far broader involvement in the functioning of the kidney, heart and central nervous system. It is currently in clinical trials with our commercial partner BAS Medical for the treatment of congestive heart failure, cervical ripening and preeclampsia. Furthermore, relaxin shows enormous promise as an antifibrotic agent which has far-reaching therapeutic conse ....Relaxin is a hormone which has long been known to have essential roles in pregnancy and birth. However it has also been demonstrated to have far broader involvement in the functioning of the kidney, heart and central nervous system. It is currently in clinical trials with our commercial partner BAS Medical for the treatment of congestive heart failure, cervical ripening and preeclampsia. Furthermore, relaxin shows enormous promise as an antifibrotic agent which has far-reaching therapeutic consequences since fibrosis is a hallmark of all forms of progressive cardiovascular and renal disease and obstructive airway disease (asthma), which collectively contribute to 40-50% of deaths in developed countries. Research into the mechanisms whereby relaxin exerts its cellular effects has been limited by the inability of researchers to identify its receptor. We now know that relaxin acts through a novel G-protein coupled receptor (GPCR) Relaxin Family Peptide Receptor (RXFP) RXFP1 and will also acts on a related receptor RXFP2. The RXFP2 receptor is actually the receptor for a hormone with similarities to relaxin, INSL3. It is essential that an appreciation of RXFP receptor function is obtained not only for its important actions in pregnancy, but also for its clinical applications. In this regard, improved understanding of how relaxin and INSL3 interact with their receptors and how these receptors function is essential. We will continue our previously successful approaches to study the interaction of relaxin and INSL3 with these 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 and INSL3 for future clinical applications. This multi-disciplinary approach will allow us to fully maximise the clinical potential of this enigmatic hormone.Read moreRead less
Molecular And Structural Basis Of Signalling By TIR Domain-containing Adaptors In TLR Pathways
Funder
National Health and Medical Research Council
Funding Amount
$666,417.00
Summary
Humans first detect the presence of pathogens and respond to them through specific pathways termed innate immune pathways. The proposed research will study proteins that participate in these pathways, in particular their three-dimensional structures and how they interact with each other, to understand how they work together to mount an immune response, and to find ways to modulate this response in infectious diseases as well as chronic inflammatory diseases.