Development Of Selective Blockers Of Acid Sensing Ion Channel 1a For The Treatment Of Stroke
Funder
National Health and Medical Research Council
Funding Amount
$702,443.00
Summary
Stroke is the second leading cause of death worldwide. In addition, stroke causes an extremely high incidence of disability in surviving victims due to the brain damage suffered during stroke. Unfortunately, no effective neuroprotective therapy is currently available for stroke patients. In this project we plan to develop novel neuroprotective agents that are effective even when used many hours after stroke, thus providing a wide therapeutic time window for treatment of stroke patients.
Exploring The Structure Activity Relationships Of Novel Trypsin Inhibitor SFTI-1 With Implications As Cancer Therapeutic
Funder
National Health and Medical Research Council
Funding Amount
$360,312.00
Summary
A novel peptide isolated from sunflower seeds has recently been shown to interact with an enzyme implicated in the growth of cancers and in particular prostate cancer. The proposed research involves developing this peptide as a therapeutic by performing a thorough analysis of the important features involved in its exciting anti-cancer activity.
Overcoming Breast Cancer Heterogeneity And Resistance Using A Novel Therapeutic Approach Targeting The Metastasis Suppressor NDRG1.
Funder
National Health and Medical Research Council
Funding Amount
$431,000.00
Summary
Breast cancer (BrCa) is the leading cause of cancer death in women and current treatments suffer from development of resistance, leading to metastatic progression. I will assess a novel treatment strategy for BrCa, targeting a gene that is able to inhibit multiple key drivers of BrCa, using a novel potent and selective anti-cancer agent. This approach has the potential to overcome resistance to current therapies and alleviate the onset of metastasis, to improve prognosis for BrCa patients.
Evaluation Of Specificity, Mechanism Of Action And Therapeutic Use Of Peptides That Disrupt T-cell Antigen Receptor
Funder
National Health and Medical Research Council
Funding Amount
$166,885.00
Summary
Molecular disorganisation of receptor assembly renders the receptor incompetent and the cell unable to perform its normal function. In autoimmune diseases where the target is self the ability to stop autoreactive T cells is a therapy. Synthetic compounds known as peptides have been developed in our laboratory with the ability to disrupt cell function and we are at the forefront of such research. We hypothesise that if you prevent the receptor from assembling properly then it will not function. T ....Molecular disorganisation of receptor assembly renders the receptor incompetent and the cell unable to perform its normal function. In autoimmune diseases where the target is self the ability to stop autoreactive T cells is a therapy. Synthetic compounds known as peptides have been developed in our laboratory with the ability to disrupt cell function and we are at the forefront of such research. We hypothesise that if you prevent the receptor from assembling properly then it will not function. The end result is the potential to develop novel drugs with new means to treat inflammation in a number of autoimmune disorders including diabetes, rheumatoid arthritis, multiple sclerosis and psoriasis. Application of this concept is not restricted to immunology or the disruption of the T-cell antigen receptor but has wider therapeutic application to other multicomponent receptors relevant in the field of oncology, endocrinology, and allergy. By design one can produce peptides that will specifically inhibit specific cellular functions based on structure-function relationships. Further research into this area will then allow design of new non-peptide chemical entities based on the original peptide sequence and structure with easier pharmacological handling properties and efficacy. This project aims to define necessary features of the peptide and test it in humans.Read moreRead less
Glutathione Transferase-derived Compounds As Therapeutic Agents
Funder
National Health and Medical Research Council
Funding Amount
$418,516.00
Summary
Inhibition of cardiac calcium ion channels may be an effective new way of improving heart performance in patients with heart failure. This project will investigate how a glutathione transferase enzyme inhibits calcium ion channels in the heart and if small fragments of a muscle specific glutathione transferase can be used to specifically modify cardiac ryanodine receptor function. These fragments will provide the basis for the development of a new therapeutic approach.
Relaxin Receptor Structural Determination To Aid Therapeutic Development
Funder
National Health and Medical Research Council
Funding Amount
$1,249,114.00
Summary
The receptor for the peptide hormone relaxin, RXFP1, is being targeted by numerous drug companies for the treatment of cardiovascular disease. However, the lack of molecular detail of how relaxin binds and activates RXFP1 is hindering new drug development. We will determine the structure of the complex of relaxin bound to RXFP1 and the mechanism by which this activates cells. The knowledge gained will aid in the design of new drugs targeting RXFP1 for the treatment of cardiovascular disease.
Epigenetic Therapies As Molecular Probes To Investigate The Molecular Pathogenesis Of Leukaemia
Funder
National Health and Medical Research Council
Funding Amount
$937,402.00
Summary
A major limitation to the success of targeted therapies in cancer is the fact that we have few if any tools to study in detail their mechanism of action within cancerous and normal cells. If we were able to visualise these drugs within cells and precisely characterise the proteins, DNA and RNA within a cell that interact with these therapies we will be able to identify strategies that can optimise their efficacy and reduce the side-effects of these treatments.
Uptake of fertility preservation procedures (eg. egg and embryo freezing) prior to cancer treatment is increasing and women will return to use these to try to conceive. Radiation may damage the uterus and there is insufficient evidence to guide the management of those exposed to intermediate doses. The aim is to improve understanding of radiation effects on the uterus which will assist clinicians with deciding whether it can support a pregnancy, or if surrogacy should be advised.
VCAM-targeted Delivery Of Recombinant CD39 To The Endothelium Is Antithrombotic, Antiinflammatory And Ameliorates Ischaemia Reperfusion Injury.
Funder
National Health and Medical Research Council
Funding Amount
$623,327.00
Summary
Blockage of arteries with clots leads to heart attacks and strokes. Reestablishment of blood supply by clot-busting drugs or mechanical interventions paradoxically causes further organ injury. This is due to toxic chemicals generated by inflammatory processes and free oxygen radicals. We have created an unique drug that selectively targets blood vessels that are injured by process. The drug will deliver blood-thinning activity and reduce inflammatory stress selectively at the site of need.
A Pharmacological Targeting Approach Implementing Albumin As A Carrier Of A Novel Chemotherapeutic
Funder
National Health and Medical Research Council
Funding Amount
$560,659.00
Summary
New drugs for cancer therapy are essential to develop that overcome resistance to standard chemotherapeutics. We have developed potent anti-cancer chelators that bind to the abundant plasma protein, albumin. Our studies showed increased tumour cell uptake of the chelator, Dp44mT, mediated by albumin. We will elucidate the mechanisms of their albumin-mediated uptake, with the aim to implement albumin nanoparticles as carriers of novel chelators to selectively target tumours.