Objectives: 1. Study means to determine, simply, which fish are ciguatoxic. ; 2. Determine if ciguatoxin from Qld waters is identical to classical ciguatoxin; whether any geographical or temporal trends 3. precise pharmacological action of ciguatoxin to improve treatment of victims
Seafood CRC: Discovery And Manipulation Of Neoparamoeba Perurans Aquaporins As A Means To Treat Amoebic Gill Disease (AGD)
Funder
Fisheries Research and Development Corporation
Funding Amount
$53,250.00
Summary
Cumulative data from other parasites suggests that blocking of Aquaporin channels (AQPs) may provide a suitable target for the use of pharmaceuticals to control these diseases. Neoparamoeba share many similarities with other pathogens. However, there is a need to correctly identify the Neoparamoeba AQPs at the molecular level, to undertake preliminary studies to show that these AQPs can be blocked preferentially (without affecting Atlantic salmon AQPs), and to show that block of the parasite AQP ....Cumulative data from other parasites suggests that blocking of Aquaporin channels (AQPs) may provide a suitable target for the use of pharmaceuticals to control these diseases. Neoparamoeba share many similarities with other pathogens. However, there is a need to correctly identify the Neoparamoeba AQPs at the molecular level, to undertake preliminary studies to show that these AQPs can be blocked preferentially (without affecting Atlantic salmon AQPs), and to show that block of the parasite AQPs results in inhibition or death of the Neoparamoeba. Central to this work and indeed to any further AGD research is a need to develop low cost, rapid and reliable assays of salmon gill cell – Neoparamoeba interactions. These in-vitro assays would lead to real dollar savings in the search for alternative AGD treatments by providing high throughput capability to assess multiple treatment options (pharmaceuticals, vaccines, chemicals). They provide a means of investigating amoebae – gill interactions as well as differential (pathogen versus host) effects of treatments. Dr Benita Vincent at CSIRO has begun pilot development of these assay systems with good early success, however, further resources are required to see this work to fruition. Objectives: 1. To clone and sequence Neoparamoeba perurans aquaporins 2. To screen a library of known aquaporin blockers against both Neoparaomoeba perurans and Atlantic salmon aquaporins in an in-vitro Xenopus oocyte system 3. To refine and establish routine protocols for an Atlantic salmon gill cell line and in vitro assay for examining amoeba-gill and treatment interactions 4. To take the best identified aquaporin blockers (from objective 2) and test these in vitro to determine if they kill or inhibit Neoparamoeba perurans without affecting Atlantic salmon cells Read moreRead less
Potential Pharmaceutical Products From Australian Beche-de-mer
Funder
Fisheries Research and Development Corporation
Funding Amount
$30,000.00
Summary
Objectives: 1. To evaluate the levels of theraputic activity in different species of Beche-de-Mer to identify the richest sources for these potential pharmaceuticals. 2. To improve the extraction and purification protocols to facilitate fractionation of Beche-de-mer species. 3. To examine different methods of post catch handling to preserve the therapeutic activities. 4. To test these stabilised fractions for therapeutic activities in animal models commonly used to trial dr ....Objectives: 1. To evaluate the levels of theraputic activity in different species of Beche-de-Mer to identify the richest sources for these potential pharmaceuticals. 2. To improve the extraction and purification protocols to facilitate fractionation of Beche-de-mer species. 3. To examine different methods of post catch handling to preserve the therapeutic activities. 4. To test these stabilised fractions for therapeutic activities in animal models commonly used to trial drugs for human use. Read moreRead less
New drugs for cancer therapy that overcome resistance to standard chemotherapeutics and stop the spread of cancer are essential to develop. My preliminary studies discovered a strategy to increase the activity and delivery of our novel compounds to enhance the killing of cancer cells. I will design innovative agents in an effort to provide more effective therapeutics with fewer side effects to reduce the pain of cancer patients undertaking chemotherapy who are in the battle of their lives.
Targeting The Metastasis Suppressor NDRG1 For The Treatment Of Pancreatic Cancer.
Funder
National Health and Medical Research Council
Funding Amount
$327,142.00
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 functions of NDRG1 in pancreatic cancer and how we can potentially target this gene with novel therapeutics being developed in our laboratory. We hope that this new approach will lead to more promising treatment options and a better outcome for those suffering from pancreatic cancer.
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.
Pharmacology Of Potential Anti-Tumour Agents: Iron And Copper Chelators Of The ApT, BpT And DpT Classes
Funder
National Health and Medical Research Council
Funding Amount
$647,137.00
Summary
Cancer cells take up more of the essential nutrients copper and iron than normal cells. Increased metabolism of these metals is linked to tumour growth progression. Our laboratory has developed compounds that bind these metals in tumours. Our studies suggest our novel compounds display a novel tumour targeting strategy which may explain their ability to also overcome drug resistance. This unique mechanism of action is crucial to understand for the development of novel anti-cancer agents.
Development Of Iron Complexes For The Treatment Of FriedreichÍs Ataxia & The Role Of Frataxin In Iron Metabolism
Funder
National Health and Medical Research Council
Funding Amount
$616,143.00
Summary
Friedreich's ataxia (FA) is a neuro- & cardio-degenerative disease where there is an accumulation of toxic iron (Fe) in the mitochondrion. Work from our current NHMRC grant showed iron plays a significant role in FA pathology In fact, the CIs dissected the mechanisms of mitochondrial iron-loading & have published 8 papers in high impact journals with 3 papers in PNAS USA in the last 2 yrs Understanding of this process has led to the design of rationalised drugs for FA This work in this Renewal c ....Friedreich's ataxia (FA) is a neuro- & cardio-degenerative disease where there is an accumulation of toxic iron (Fe) in the mitochondrion. Work from our current NHMRC grant showed iron plays a significant role in FA pathology In fact, the CIs dissected the mechanisms of mitochondrial iron-loading & have published 8 papers in high impact journals with 3 papers in PNAS USA in the last 2 yrs Understanding of this process has led to the design of rationalised drugs for FA This work in this Renewal could lead to novel therapies for FARead moreRead less
Drug Targeting To Sites Of Lymph-adipose Interaction To Transform The Treatment Of Disease
Funder
National Health and Medical Research Council
Funding Amount
$515,172.00
Summary
Insulin resistance (IR) underpins the development of inadequately treated heart and metabolic diseases such as type 2 diabetes. Recently we demonstrated that high fat diets promote increased leakage of fluid from lymph vessels to abdominal fat, and that increased access of lymph fluid to fat stimulates fat expansion and changes in fat function that promote IR. This project seeks to optimise novel drug delivery strategies that target lymph and fat and more effectively treat IR.