Mechanisms Of Oxidised Protein Accumulation In Ageing Cells
Funder
National Health and Medical Research Council
Funding Amount
$429,000.00
Summary
Australia has one of the world's most rapidly ageing populations. It is estimated that in 30 years time over 30% of the population will be over 65; many will suffer from a debilitating, age-related disease. The diseases of ageing represent one of the major health challenges this century. Despite their increasing incidence, our understanding of the underlying causes is limited. A common feature is the accumulation of damaged proteins in cells and tissues. Damaged proteins are usually broken down ....Australia has one of the world's most rapidly ageing populations. It is estimated that in 30 years time over 30% of the population will be over 65; many will suffer from a debilitating, age-related disease. The diseases of ageing represent one of the major health challenges this century. Despite their increasing incidence, our understanding of the underlying causes is limited. A common feature is the accumulation of damaged proteins in cells and tissues. Damaged proteins are usually broken down by the cells and replaced, but in many age-related diseases this process fails. The most common source of protein damage is attack by oxygen-derived free radicals. These are by-products of our body's need for oxygen and can originate from atmospheric pollutants. Oxygen rusts metal, makes fat go rancid and can cause irreparable damage to proteins and other biological molecules. Free radical damage contributes to the development of many age-related diseases such as atherosclerosis and neurodegenerative diseases such as Alzheimer's disease. The accumulation of damaged proteins can cause cell death. Our knowledge of the mechanisms by which cells remove proteins damaged by oxygen and the reasons for their accumulation is limited. In this project we will use a novel technique we have developed to generate oxidised proteins in ageing cells. We will identify cellular mechanisms required for the efficient removal of damaged proteins and those mechanisms which fail in ageing cells. We will focus on a group of proteins which protect damaged proteins from aggregating and accumulating and we will examine how we can prevent the accumulation of oxidised proteins by stimulating the body s defence mechanisms. Since the population of Australia is ageing, diseases of ageing are going to consume an increasing amount of the national health budget. A better knowledge of these cellular mechanisms will allow us to design effective prevention and treatment strategies which are at present lacking.Read moreRead less
Single-session Introduction of Mutations in Parallel Lines (SIMPL). This project aims to develop a novel method for markedly accelerating production of genetically modified mice, which are a key 'tool' for studying biological processes and diseases. The work plans to take CRISPR, the latest gene-editing technique, to the next level by developing a novel CRISPR-based method to generate different mouse strains with distinct variations of the same gene sequences, at a fraction of the present cost a ....Single-session Introduction of Mutations in Parallel Lines (SIMPL). This project aims to develop a novel method for markedly accelerating production of genetically modified mice, which are a key 'tool' for studying biological processes and diseases. The work plans to take CRISPR, the latest gene-editing technique, to the next level by developing a novel CRISPR-based method to generate different mouse strains with distinct variations of the same gene sequences, at a fraction of the present cost and time. This project should overcome a major barrier to studying gene function with unprecedented detail, thereby opening new avenues for future research into biological processes. Thus, the outcomes from this project should impact on the entire field of biomedical research, and advance Australia's biotech industry.Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE190100985
Funder
Australian Research Council
Funding Amount
$409,574.00
Summary
Targeted genome editing using engineered CRISPR-Cas endonucleases. This project aims to study the generation of targeted and cell-specific endonucleases. CRISPR-Cas endonucleases have revolutionised the field of genome engineering due to programming simplicity based on a short guide RNA and high cleavage efficiency. This project will combine the use of two technologies in genome engineering and antibody therapeutics to generate new antibody-targeted endonucleases that modify cellular genomes wit ....Targeted genome editing using engineered CRISPR-Cas endonucleases. This project aims to study the generation of targeted and cell-specific endonucleases. CRISPR-Cas endonucleases have revolutionised the field of genome engineering due to programming simplicity based on a short guide RNA and high cleavage efficiency. This project will combine the use of two technologies in genome engineering and antibody therapeutics to generate new antibody-targeted endonucleases that modify cellular genomes with high efficacy and specificity. This project will provide new and intriguing insights into cellar function, with broad applications in basic research and biotechnology.Read moreRead less
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.
The design of targetable epigenetic modifiers. The project aims to engineer enzymes as valuable tools for understanding gene expression mechanisms and potentially a technology for altering gene expression in plants, animals or humans in a targetable manner. The genetic information encoded in the DNA of all complex organisms has been shown to be augmented by decorations on both DNA and the histone proteins that package DNA. This so-called epigenetic information is important but not well understoo ....The design of targetable epigenetic modifiers. The project aims to engineer enzymes as valuable tools for understanding gene expression mechanisms and potentially a technology for altering gene expression in plants, animals or humans in a targetable manner. The genetic information encoded in the DNA of all complex organisms has been shown to be augmented by decorations on both DNA and the histone proteins that package DNA. This so-called epigenetic information is important but not well understood. The project plans to design highly specific and targetable enzymes that can interrogate and manipulate epigenetic information in living cells. Understanding the regulation of gene expression and controlling the expression of chosen genes may form a foundation for applications in agriculture, biology and medicine.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
A New Platform for Developing a Compound Against Herpes Simplex Virus. This project aims to further explore the research team’s recent fundamental discovery of a protein found naturally in an Australian abalone that inhibits viral entry by blocking three key viral glycoproteins. We would aim to utilise this knowledge towards development of a new class of therapeutics against Herpes simplex viruses (HSV) and their consequent infections. The new therapeutics could overcome the low bioavailability ....A New Platform for Developing a Compound Against Herpes Simplex Virus. This project aims to further explore the research team’s recent fundamental discovery of a protein found naturally in an Australian abalone that inhibits viral entry by blocking three key viral glycoproteins. We would aim to utilise this knowledge towards development of a new class of therapeutics against Herpes simplex viruses (HSV) and their consequent infections. The new therapeutics could overcome the low bioavailability of current drugs and thus significantly shorten the recurrence period. Such new drugs may have broad applicability.Read moreRead less
Boosting C4 photosynthesis to climate proof crop yields. Building next generation C4 crops, such as maize, sugarcane and sorghum, to cope with drought and heat stress is requisite to ensure the supply of food and fodder. Here we will increase the content and / or catalytic efficiency of the primary carboxylase of C4 photosynthesis (PEPC) that supplies CO2 to the carbon concentrating mechanism and ensures high photosynthetic rates. We will develop new SynBio tools to create and test novel PEPC is ....Boosting C4 photosynthesis to climate proof crop yields. Building next generation C4 crops, such as maize, sugarcane and sorghum, to cope with drought and heat stress is requisite to ensure the supply of food and fodder. Here we will increase the content and / or catalytic efficiency of the primary carboxylase of C4 photosynthesis (PEPC) that supplies CO2 to the carbon concentrating mechanism and ensures high photosynthetic rates. We will develop new SynBio tools to create and test novel PEPC isoforms with desirable properties. Ultimately, the project aims to identify isoforms that improve plant fitness under stress conditions. Optimising PEPC activity will provide next generation solutions to improve water balance and carbon assimilation to keep C4 crops productive under future climates.Read moreRead less