Pharmacological Targeting Via AKT, PTEN, And TGF-beta Pathway Integration Using Novel Therapeutics
Funder
National Health and Medical Research Council
Funding Amount
$634,875.00
Summary
We have identified potentially important interactions of cellular pathways that vary between individual sufferers, but which also provide common molecular targets for novel drug development. Our suite of novel and potent drugs that markedly and selectively inhibit cancer cell growth will be studied to determine if these pharmaceutical agents act to inhibit tumour cell proliferation by targeting common effector molecules of integrated cellular pathways.
Investigating the functional interaction between vasopressin and angiotensin receptors. Kidney disease resulting from diabetes is a major health issue for Australians, and indigenous Australians in particular. This project aims to enable improved therapies to be developed, as well as better inform doctors regarding the use of potential combinations of existing pharmaceuticals to treat this condition.
Systematic evaluation of whether in vitro methods can predict in vivo opioid analgesic efficacy, safety and tolerability. It is estimated that chronic pain affects one in five individuals in the general community in Australia and worldwide, with prevalence rates correlated directly with advancing age. Chronic pain not only adversely affects the quality of life of individuals but it also places a large economic burden on our healthcare system. Development and validation of an in vitro method to ....Systematic evaluation of whether in vitro methods can predict in vivo opioid analgesic efficacy, safety and tolerability. It is estimated that chronic pain affects one in five individuals in the general community in Australia and worldwide, with prevalence rates correlated directly with advancing age. Chronic pain not only adversely affects the quality of life of individuals but it also places a large economic burden on our healthcare system. Development and validation of an in vitro method to successfully identify novel morphine-like strong analgesics with a reduced propensity for producing respiratory depression or constipation, has the potential to not only improve pain management for individuals and to reduce the economic burden of chronic pain on the Australian healthcare system, but it is also likely to produce direct economic benefits to our nation. Read moreRead less
Pre-clinical Development Of A Novel Second Generation Chemotherapeutic For Cancer Therapy
Funder
National Health and Medical Research Council
Funding Amount
$584,907.00
Summary
Cancer cells have a high iron requirement for DNA synthesis and many clinical trials have shown that iron chelators are effective anti-cancer drugs. Their potential to act as anti-tumour agents has been confirmed by the entrance of the iron chelator, Triapine, into widespread NCI clinical trials. In this NHMRC Development Grant, we will perform toxicological studies to enable clinical trials of our most potent and selective anti-cancer agent to commence.
Pharmacological Targeting Of Integrated Oncogenic And Tumour Suppressive Pathways Using Novel Therapeutics.
Funder
National Health and Medical Research Council
Funding Amount
$510,953.00
Summary
We will investigate NDRG1, a novel molecular target that has been demonstrated to inhibit the progression of numerous cancers. We aim to better understand the underlying function of NDRG1 in pancreatic cancer and how we can potentially target this gene with novel therapeutics being developed in our lab. We hope that this new approach will lead to promising treatments and a better outcome for those suffering from pancreatic cancer.
Investigating The Effects Of Macrolides On Excessive Synthesis And Secretion Of Airway Mucins Using Novel Ex Vivo And In Vivo Approaches
Funder
National Health and Medical Research Council
Funding Amount
$520,821.00
Summary
Many people have difficulty breathing because the airway tubes that move air in and out of their lungs are blocked by excessive amounts of sticky mucus. Our project will use new techniques developed in our laboratories to investigate whether a group of medicines called “macrolides” can prevent the excessive production and release of mucus in the airways, and thus be beneficial in treating asthma, and potentially other lung diseases.
Probing the role of dynamics in protein modulation of GPCR phenotype . Life relies upon the fundamental ability to convert external stimuli into an appropriate biological response. Such stimuli are transmitted by cell surface proteins (receptors), which convert this stimulus into an intracellular signal. The largest group of cell surface receptors is the G protein-coupled receptor (GPCR) family. Despite advances in GPCR structure determination, many questions regarding the structural basis of GP ....Probing the role of dynamics in protein modulation of GPCR phenotype . Life relies upon the fundamental ability to convert external stimuli into an appropriate biological response. Such stimuli are transmitted by cell surface proteins (receptors), which convert this stimulus into an intracellular signal. The largest group of cell surface receptors is the G protein-coupled receptor (GPCR) family. Despite advances in GPCR structure determination, many questions regarding the structural basis of GPCR function and signalling remain unanswered. The primary outcome of this project is to provide mechanistic insight into the dynamics of GPCR ligand recognition and activation to advance our understanding of GPCR signal transduction, a fundamental biological process for all living organisms.Read moreRead less
Bias and allostery at the calcium sensing receptor. This project aims to provide a mechanistic and dynamic picture of the structure, function and physiology of the human calcium sensing receptor (CaSR), which is critical for vertebrate life. By responding to chemicals in the body, it acts as a universal nutrient sensor to maintain extracellular calcium homeostasis and mediate biological functions, including neurotransmission, inflammation, digestion, blood pressure and development. However, it i ....Bias and allostery at the calcium sensing receptor. This project aims to provide a mechanistic and dynamic picture of the structure, function and physiology of the human calcium sensing receptor (CaSR), which is critical for vertebrate life. By responding to chemicals in the body, it acts as a universal nutrient sensor to maintain extracellular calcium homeostasis and mediate biological functions, including neurotransmission, inflammation, digestion, blood pressure and development. However, it is not known how this single receptor controls the actions of multiple ligands to mediate numerous functions. By elucidating the roles of the CaSR and its ligands, this project aims to better understand fundamental physiological processes.Read moreRead less
Understanding the mechanisms of class B GPCR-transducer coupling. Current effort in developing drugs targeting G protein-coupled receptors (GPCRs) often result in low success rate due to the lack of understanding of the complexity and the spatiotemporal control of receptor function. The research program aims to understand the molecular mechanisms of receptor/transducer selectivity. The proposal integrated multi-disciplinary approaches to provide a deeper understanding of how the receptor is acti ....Understanding the mechanisms of class B GPCR-transducer coupling. Current effort in developing drugs targeting G protein-coupled receptors (GPCRs) often result in low success rate due to the lack of understanding of the complexity and the spatiotemporal control of receptor function. The research program aims to understand the molecular mechanisms of receptor/transducer selectivity. The proposal integrated multi-disciplinary approaches to provide a deeper understanding of how the receptor is activated responding to different ligands. The anticipated outcome including an enhanced capacity for understanding the fundamental biology, a stronger national and international collaborations. This will provide significant benefits including expanded basic knowledge and improvements in drug development efficiency. Read moreRead less
Formyl Peptide Receptor Biased Agonists As Novel Cardioprotection From Myocardial Infarction
Funder
National Health and Medical Research Council
Funding Amount
$948,291.00
Summary
Heart attack is caused by a blocked heart blood vessel. Current therapy focuses on rapid reopening of the vessel, to allow blood supply to return. However, even if this is successful, affected patients are often left with impaired heart muscle pumping function, ultimately progressing to heart failure. We have discovered an exciting new mechanism to protect heart muscle from injury and preserve its function, and we plan to develop new drugs for heart attack based on this mechanism.