Targeted Disruption Of Lipoxygenase Enzymes To Prevent Oxidative Stress-mediated Pathologies In The Male Germline
Funder
National Health and Medical Research Council
Funding Amount
$408,768.00
Summary
An estimated 80 million individuals suffer from infertility globally with at least 50% of these cases due to defects in sperm function. Unfortunately, due to a severe lack of knowledge surrounding sperm biology and dysfunction, no successful curative or preventative measures have been established. My project will study why sperm cells die and investigate new ways to limit cellular stress so we can develop new therapeutic strategies to mitigate the growing problems in male reproductive health.
Targeting PI3K-regulated Small Non-coding RNAs To Restore Cardiac Function
Funder
National Health and Medical Research Council
Funding Amount
$610,204.00
Summary
Heart failure affects approximately 2.4% of the adult population and over 11% of people over 80 years old. The majority of existing therapies slow, rather than reverse heart failure progression. The primary goal of this study is to determine whether regulating novel regulatory genes can enhance cardiac function in a setting of heart failure. Ultimately, technologies that target these genes may lead to innovative pharmacotherapies in the clinical management of heart failure.
Can Skin Infection With Group A Streptococcus Cause Acute Rheumatic Fever?
Funder
National Health and Medical Research Council
Funding Amount
$459,450.00
Summary
It is traditionally taught that the cause of acute rheumatic fever (ARF) is always infection of the throat with the bacterium group A streptococcus (GAS). However, in Aboriginal communities of the Top End of the Northern Territory the incidence of ARF is the highest reported in the world, yet GAS is uncommonly isolated from the throat. There is further information to suggest that GAS skin sores may underlie many cases of ARF. If this were proven, it would completely alter the traditional view of ....It is traditionally taught that the cause of acute rheumatic fever (ARF) is always infection of the throat with the bacterium group A streptococcus (GAS). However, in Aboriginal communities of the Top End of the Northern Territory the incidence of ARF is the highest reported in the world, yet GAS is uncommonly isolated from the throat. There is further information to suggest that GAS skin sores may underlie many cases of ARF. If this were proven, it would completely alter the traditional view of the cause of ARF, and have important implications for prevention of ARF around the world. Presently, these approaches focus on diagnosing and treating sore throat, but no country has proven that such a program can be successful in substantially reducing new cases of ARF. If it was known that skin infection could lead to ARF, then countries (including Australia) could emphasise the importance of skin health programs. A further benefit of this knowledge would be to influence GAS vaccine development, which presently is largely focused on the prevention of sore throat. A different possibility has recently been raised - that the cause of ARF may not always be GAS, but instead that the related bacteria GCS and GGS may have the potential to cause this disease. Proof of this hypothesis would even more dramatically alter our understanding of disease causation, prevention, and vaccine development. We propose to determine the cause of ARF in Aboriginal communities by regularly swabbing families of people with a history of ARF, and using genetic fingerprinting of the bacteria from the skin and throat swabs. When cases of ARF occur, we will be able to determine the site and type of infection that precipitated the attack. We will conduct a related study in more communities, in which we will swab family members of people with ARF and of control families (without ARF) to determine the bacteria most commonly isolated from ARF families.Read moreRead less
The Effect Of Exogenous Hormones, Smoking And HPV On The Incidence Of Screen Detected Pre-invasive Cervical Cancer.
Funder
National Health and Medical Research Council
Funding Amount
$1,201,168.00
Summary
Cervical cancer is one of the leading causes of cancer death in women internationally. About 15,000 women are detected in NSW annually as having pre-invasive cervical cancer (cervical intraepithelial neoplasia (CIN) grade I, II or III). Infection with certain high risk human papillomaviruses is known to be necessary for the development of cervical cancer. In addition, recent long term exposure to smoking and to hormonal contraception are two new factors considered as independent risk factors for ....Cervical cancer is one of the leading causes of cancer death in women internationally. About 15,000 women are detected in NSW annually as having pre-invasive cervical cancer (cervical intraepithelial neoplasia (CIN) grade I, II or III). Infection with certain high risk human papillomaviruses is known to be necessary for the development of cervical cancer. In addition, recent long term exposure to smoking and to hormonal contraception are two new factors considered as independent risk factors for the disease. Hormone replacement therapy (HRT) preparations taken around the menopause are a similar composition to hormonal contraceptives, (oestrogen and progestogen), therefore women on HRT may also be at increased risk. No comprehensive study exists internationally to measure the relative importance of these exogenous hormones on the development of pre-invasive cervical cancer in a way that is of public health relevance (e.g. recent long-term use of oral contraceptives and time since stopped, and among smokers and non-smokers). No Australian data are available on the proportion of women who are current users of hormonal contraceptives or HRT. No local prevalence data on the major high risk HPV subtypes (e.g. 16, 18, 33, 45) are available for Australia to describe its distribution and to inform the cervical screening program and future vaccine initiatives. The NSW Pap Test Register holds the screening history of all women on the cervical screening program, hence this is an ideal source for recruiting a representative sample into a study. We wish to conduct a large study of ~2600 NSW women using the NSW Pap Test Register to measure the relative importance of hormones, smoking and HPV infection on the development of CIN II or III.Read moreRead less
Shallow water carbonate sediment dissolution in the global carbon cycle. Carbonate sediment dissolution is a globally significant process, but poorly understood in shallow marine waters. This project will determine whether the combined effect of organic matter, ocean acidification and pore water flow in shallow water carbonate sediments increases the release of calcium and alkalinity to the ocean. This project is significant because this release has not previously been accounted for and may lead ....Shallow water carbonate sediment dissolution in the global carbon cycle. Carbonate sediment dissolution is a globally significant process, but poorly understood in shallow marine waters. This project will determine whether the combined effect of organic matter, ocean acidification and pore water flow in shallow water carbonate sediments increases the release of calcium and alkalinity to the ocean. This project is significant because this release has not previously been accounted for and may lead to an additional uptake of atmospheric carbon dioxide into the global ocean, maybe some additional buffering against ocean acidification, but unfortunately, maybe also a loss of carbonate ecosystems. The outcomes of this project will make a significant contribution to our understanding of the global carbon cycle.
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Can eco-evolutionary theories explain outcomes of microbiome coalescence . Environmental microbial communities are among the most abundant and diverse natural communities, responsible for many ecologically and economically important ecosystem functions, including primary productivity and climate regulation. This project aims to identify the biotic and abiotic factors that regulate community and functional outcomes of microbiome coalescence (the mixing of two different communities) caused by natu ....Can eco-evolutionary theories explain outcomes of microbiome coalescence . Environmental microbial communities are among the most abundant and diverse natural communities, responsible for many ecologically and economically important ecosystem functions, including primary productivity and climate regulation. This project aims to identify the biotic and abiotic factors that regulate community and functional outcomes of microbiome coalescence (the mixing of two different communities) caused by natural and anthropogenic activities. The outcomes will provide a unifying ecological framework to predict variation in microbiomes across different scales, ecosystem types and disturbances, and will generate critical knowledge for the development of effective microbiome products, a rapidly growing industryRead moreRead less
The Structural Basis For Glutamate Transporter Function
Funder
National Health and Medical Research Council
Funding Amount
$373,144.00
Summary
Glutamate transporters are vacuum cleaners in the brain that suck the neurotransmitter glutamate into cells. When the glutamate vacuum breaks down or becomes blocked, glutamate levels outside cells increase, leading to cell death in the brain. This process underlies the damage in many brain diseases including Alzheimer’s disease and stroke. The aim of this project is to understand the mechanism of the glutamate vacuum cleaner so we can develop therapeutics to fix it when it breaks down.
Placental nutrient transport shows how complex traits evolve. This project aims to use amino acid transport in the vertebrate placenta as a model to demonstrate how genes are recruited and modified to produce a major organ. Using an innovative combination of a new technology, selected reaction monitoring, and transcriptomic and molecular approaches, plus carefully selected Australian species pairs, this project will study the evolution of a complex trait (placental amino acid transport). The pr ....Placental nutrient transport shows how complex traits evolve. This project aims to use amino acid transport in the vertebrate placenta as a model to demonstrate how genes are recruited and modified to produce a major organ. Using an innovative combination of a new technology, selected reaction monitoring, and transcriptomic and molecular approaches, plus carefully selected Australian species pairs, this project will study the evolution of a complex trait (placental amino acid transport). The project will provide fundamental advances in our knowledge of the nutrient transport during pregnancy that is required to produce a healthy baby.Read moreRead less
Lively reproduction: do common molecules underlie all vertebrate live birth? Most animals lay eggs, but some (most mammals, including humans and some reptiles) give birth to live young. This project will reveal the molecules underlying the evolution of live birth and fundamental processes of early pregnancy, which potentially will lead to future developments in reproductive science.
Dissolution of CaCO3 in sediments in an acidifying ocean. Dissolution of calcium carbonate (CaCO3) in sediments in the context of ocean acidification is poorly understood. This project will use in situ advective benthic chamber incubations and experimental manipulations under future ocean acidification scenarios to determine the controls on the dissolution of CaCO3 in sediments. This project is significant because changes in the dissolution of CaCO3 in sediments in an acidifying ocean are at lea ....Dissolution of CaCO3 in sediments in an acidifying ocean. Dissolution of calcium carbonate (CaCO3) in sediments in the context of ocean acidification is poorly understood. This project will use in situ advective benthic chamber incubations and experimental manipulations under future ocean acidification scenarios to determine the controls on the dissolution of CaCO3 in sediments. This project is significant because changes in the dissolution of CaCO3 in sediments in an acidifying ocean are at least as important, and potentially more important, than calcification to the future accretion and survival of carbonate ecosystems. It is expected that outcomes of this project will significantly advance our understanding of the drivers of the dissolution of CaCO3 in sediments and the functioning of globally important carbonate ecosystems.Read moreRead less