Immunological mechanisms underlying the protective immune responses induced by botulinum oil adjuvanted vaccine. Botulism is recognised as an important bacterial pathogen in commercial beef cattle in Australia and around the world. Development of affective, well-researched vaccine against Clostridium botulinum is a high priority for the cattle industry. A novel oil adjuvanted vaccine (Singvac from Fort Dodge Pty Ltd) has advantage over conventional vaccines as it provides full protection follo ....Immunological mechanisms underlying the protective immune responses induced by botulinum oil adjuvanted vaccine. Botulism is recognised as an important bacterial pathogen in commercial beef cattle in Australia and around the world. Development of affective, well-researched vaccine against Clostridium botulinum is a high priority for the cattle industry. A novel oil adjuvanted vaccine (Singvac from Fort Dodge Pty Ltd) has advantage over conventional vaccines as it provides full protection following a single administration. The aims of this study are to investigate the immunological mechanisms underlying the protective response by this novel vaccine using bovine and murine models. This study will discover new control measures for botulism in Australia.Read moreRead less
Melanotransferrin: A “Missing Link” And A Novel Pharmacological Target For Treatment
Funder
National Health and Medical Research Council
Funding Amount
$613,848.00
Summary
Despite >30 years of research, the precise function of the protein, melanotransferrin (MTf), is unknown. However, we have breakthrough evidence that MTf stimulates WNT signalling as a major driver in cancer progression. We will investigate this hypothesis, which will underpin new cancer therapies. Indeed, we designed a new class of drugs that target the WNT pathway via up-regulating the WNT inhibitor, NDRG1. This drug (DpC) inhibits MTf expression to block tumour cell growth and metastasis.
Development of new tools for surveillance of chlamydial infections in sheep. This project aims to improve health in sheep and reduce on-farm losses for Australian producers, by developing new serological tests for chlamydial infections in sheep. These infections can result in significant on-farm losses and loss of trade in the live export industry. Currently, surveillance of chlamydial infections is hindered by outdated serological tools that are unreliable and difficult to interpret. The ser ....Development of new tools for surveillance of chlamydial infections in sheep. This project aims to improve health in sheep and reduce on-farm losses for Australian producers, by developing new serological tests for chlamydial infections in sheep. These infections can result in significant on-farm losses and loss of trade in the live export industry. Currently, surveillance of chlamydial infections is hindered by outdated serological tools that are unreliable and difficult to interpret. The serological tests to be developed aim to be species-specific tests to detect the most important chlamydial sheep pathogens. This in turn endeavours to improve domestic surveillance, reducing on-farm losses and costs, and improve market opportunities for Australian sheep exporters as well as informing veterinary populations on best practice treatment.Read moreRead less
Biotechnology applications in the veterinary pharmaceutical industry: Pharmacological manipulation of ovarian function in domestic animals. The purpose of this research is to develop a humane, simple, safe, effective means of sterilizing female domestic animals without the need for surgical intervention. This novel experimental strategy is to target the supply of dormant eggs in the ovaries of female mammals. Every female mammal is born with a finite supply of eggs in the ovarian cortex. These c ....Biotechnology applications in the veterinary pharmaceutical industry: Pharmacological manipulation of ovarian function in domestic animals. The purpose of this research is to develop a humane, simple, safe, effective means of sterilizing female domestic animals without the need for surgical intervention. This novel experimental strategy is to target the supply of dormant eggs in the ovaries of female mammals. Every female mammal is born with a finite supply of eggs in the ovarian cortex. These cells cannot divide and so when this store is exhausted, reproduction ceases. Our strategy is to develop pharmaceutical reagents that will destroy this dormant egg population, thereby rendering the animals instantaneously and irreversibly infertile.Read moreRead less
What role does wildlife play in emergency disease? The case of the feral pig. Wildlife populations have been responsible for many disease emergencies with economic and human health impacts, but our current understanding limits their management. This project focuses on the feral pig, an introduced wildlife species. It will develop an understanding of disease spread in feral pigs and from feral pigs to cattle. Using feral pig disease genetics, climate and environmental data, disease spread models ....What role does wildlife play in emergency disease? The case of the feral pig. Wildlife populations have been responsible for many disease emergencies with economic and human health impacts, but our current understanding limits their management. This project focuses on the feral pig, an introduced wildlife species. It will develop an understanding of disease spread in feral pigs and from feral pigs to cattle. Using feral pig disease genetics, climate and environmental data, disease spread models will be developed. These models will be used to better manage emergency disease outbreaks in feral pigs and other wildlife species. This project will deliver practical outcomes, such as the best method of discovering disease and the most effective methods to control emergency animal diseases in wildlife and domestic animals.Read moreRead less
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
Environmental contamination and pig disease: an Australian microbe evolves. The Australian pig industry produces pork commodities from over 4.75 million pigs per year. Infectious diseases in industrial-scale piggeries can have a devastating effect on pork production, particularly on feed conversion efficiency and growth rates, and can pose downstream environmental contamination and food safety risks. This project aims to assess a current infectious disease problem in pigs by studying a microbe t ....Environmental contamination and pig disease: an Australian microbe evolves. The Australian pig industry produces pork commodities from over 4.75 million pigs per year. Infectious diseases in industrial-scale piggeries can have a devastating effect on pork production, particularly on feed conversion efficiency and growth rates, and can pose downstream environmental contamination and food safety risks. This project aims to assess a current infectious disease problem in pigs by studying a microbe that appears to have uniquely evolved in Australia. These results could inform the rational design of monitoring, prevention and treatment strategies to minimise infection outbreaks in Australian pigs and may result in production benefits to the pork industry, reduced environmental microbial contamination and safer food.Read moreRead less
Examination Of The Molecular Pharmacology Of Anthracyclines Induced Via Their Interaction With Iron
Funder
National Health and Medical Research Council
Funding Amount
$618,401.00
Summary
Anthracyclines are highly effective anti-cancer drugs, but their use is limited by toxic effects on the heart. This is thought to be due to these drugs directly binding iron (Fe). Indeed, we showed that anthracyclines induced marked changes in the way heart cells utilise Fe (DR1-3, 38; Mol. Pharmacol. 2002, 2003, 2004, 2005). We were the first to show that anthracyclines prevent Fe release from the criticial Fe storage protein ferritin. This prevents the use of Fe for vital processes eg. DNA and ....Anthracyclines are highly effective anti-cancer drugs, but their use is limited by toxic effects on the heart. This is thought to be due to these drugs directly binding iron (Fe). Indeed, we showed that anthracyclines induced marked changes in the way heart cells utilise Fe (DR1-3, 38; Mol. Pharmacol. 2002, 2003, 2004, 2005). We were the first to show that anthracyclines prevent Fe release from the criticial Fe storage protein ferritin. This prevents the use of Fe for vital processes eg. DNA and haem synthesis. Hence, this effect probably contributes to the cytotoxic activity of anthracyclines on the heart. We showed that novel drugs developed in my lab that bind Fe called chelators show high activity in animals (DR4) and prevent anthracycline-mediated Fe accumulation in ferritin. Importantly, Fe chelators have been shown to inhibit anthracycline-mediated cardiotoxicity. Indeed, the clinically used cardioprotective agent, ICRF-187, is actually an Fe chelator (5, DR6). However, ICRF-187 is not totally successful in terms of its cardioprotective effects and can cause myelosuppression (5, DR6). While the clinically used chelator, desferrioxamine (DFO), can prevent anthracycline-mediated cardiotoxicity, its poor membrane permeability limits its effectiveness. Our chelators are highly permeable and overcome the disadvantages of DFO (DR4). Thus, they are vital to examine for preventing anthracycline-mediated cardiotoxicity. In this proposal we will examine the changes in Fe metabolism induced by anthracyclines and test the hypothesis that novel Fe chelators may prevent the cardiotoxicity of these agents. We also aim to be the first to assess if preparation of anthracyclines which cannot bind iron prevents their cardiotoxicity. This will be done by preparing metal complexes of these drugs which prevent Fe-binding eg. anthracycline-zinc complexes. These studies are important for the development of less cardiotoxic forms of these very useful anti-tumour agents.Read moreRead less
Development Of Iron Chelators For The Treatment Of Friedreichs Ataxia And The Role Of Frataxin In Iron Metabolism
Funder
National Health and Medical Research Council
Funding Amount
$550,987.00
Summary
Friedreich's ataxia (FA) is a neuro- and cardio-degenerative disease where there is an accumulation of toxic Fe in the mitochondrion. Excitingly, work from our current NHMRC grant showed iron plays a significant role in FA pathology. Importantly, we developed new drugs (Fe chelators) which rescue the cardiac pathology of FA in an animal model. Studies will now assess if our drugs prevent the neurodegeneration of FA in another animal model. This work could lead to novel therapies for FA.