Molecular dissection of the effects of alpha-actinin-3 deficiency on normal variation in skeletal muscle function. We will study the mechanisms by which a common genetic variant influences muscle bulk, muscle strength and the metabolic efficiency of muscle in the general population. Common genetic variants that influence skeletal muscle function have major potential public health implications as they are likely to influence individuals' response to exercise and diet, and to contribute to suscept ....Molecular dissection of the effects of alpha-actinin-3 deficiency on normal variation in skeletal muscle function. We will study the mechanisms by which a common genetic variant influences muscle bulk, muscle strength and the metabolic efficiency of muscle in the general population. Common genetic variants that influence skeletal muscle function have major potential public health implications as they are likely to influence individuals' response to exercise and diet, and to contribute to susceptibility to common diseases such as obesity, diabetes, and the loss of muscle strength in the elderly. In addition, the identification of genetic factors that influence muscle bulk in vertebrates has implications for breeding programs in sheep and cattle and may provide commercial benefit to the livestock industry.Read moreRead less
The mucosal immune system of fish: analysis of the immune repertoire in gut-and gill-associated lymphoid tissues in trout. Infectious disease causes major economic loss to the aquaculture industry, highlighting the need for effective vaccination strategies. While oral or immersion vaccination represents the most cost effective means of protecting fish against infectious disease there are problems associated with inducing an effective immune response in fish that will assist our industry partner ....The mucosal immune system of fish: analysis of the immune repertoire in gut-and gill-associated lymphoid tissues in trout. Infectious disease causes major economic loss to the aquaculture industry, highlighting the need for effective vaccination strategies. While oral or immersion vaccination represents the most cost effective means of protecting fish against infectious disease there are problems associated with inducing an effective immune response in fish that will assist our industry partner (Novartis Animal Vaccines Ltd) to develop improved fish vaccines. The project will provide postgraduate training in the area of fish immunology that is vital to the developing Australian aquaculture industry.Read moreRead less
The transcriptional co-repressor C-terminal Binding Protein (CtBP) in metabolic control. This project will provide insights into the genes that regulate the storage of fat. We will learn about basic biology but will also discover mechanisms that may be used to influence fat storage in human health. We will also consolidate Australia's expertise in the use of the genetic model organism, the worm C. elegans, and validate the findings in mammalian systems. Finally, the process of training young sci ....The transcriptional co-repressor C-terminal Binding Protein (CtBP) in metabolic control. This project will provide insights into the genes that regulate the storage of fat. We will learn about basic biology but will also discover mechanisms that may be used to influence fat storage in human health. We will also consolidate Australia's expertise in the use of the genetic model organism, the worm C. elegans, and validate the findings in mammalian systems. Finally, the process of training young scientists in these modern systems, will also equip future researchers to make additional contributions to Australia's research output.Read moreRead less
RNA splicing: factors and mechanisms. Most primary gene transcripts must have their noncoding intronic sequences spliced out before the mRNA can be translated. Moreover, alternative splicing enables cells to generate a far more proteins than there are genes in the nucleus. Based on our proven success with ZNF265 we will isolate novel RNA interactors and their partners, colocalize these in intranuclear compartments, and elucidate their effect on pre-mRNA splicing. This will provide timely spin-of ....RNA splicing: factors and mechanisms. Most primary gene transcripts must have their noncoding intronic sequences spliced out before the mRNA can be translated. Moreover, alternative splicing enables cells to generate a far more proteins than there are genes in the nucleus. Based on our proven success with ZNF265 we will isolate novel RNA interactors and their partners, colocalize these in intranuclear compartments, and elucidate their effect on pre-mRNA splicing. This will provide timely spin-offs to the Human genome Project and EST sequence information, where the finding of only approx. 30,000 genes in our genome highlights the important role of alternative splicing in generating the large proteome repertoire of cells. This will bring considerable benefits to science, society, and the biotech industry.Read moreRead less
A new mechanism of gene regulation. This project will advance our knowledge of how genes are switched on and off, by focusing on a very common class of gene regulatory proteins known as zinc finger proteins. The results of this study will improve our understanding of the fundamental molecular events that underpin gene regulation and how we might control it in fields such as biotechnology and gene therapy.
New mechanisms of DNA recognition by zinc-finger domains. The work described in this proposal carries long-term benefits to the health of Australians. Many debilitating diseases, including many varieties of cancer, arise as a result of a breakdown in the normal regulation of gene transcription. It is only once we have a thorough understanding of transcriptional regulation in normal organisms that we will be in a position to devise effective therapies to deal with the disorders that result from a ....New mechanisms of DNA recognition by zinc-finger domains. The work described in this proposal carries long-term benefits to the health of Australians. Many debilitating diseases, including many varieties of cancer, arise as a result of a breakdown in the normal regulation of gene transcription. It is only once we have a thorough understanding of transcriptional regulation in normal organisms that we will be in a position to devise effective therapies to deal with the disorders that result from aberrant gene expression. Our proposed research program also provides the opportunity to train younger scientists in state-of-the-art molecular and structural biology, thus representing a significant national benefit. Read moreRead less
Molecular mechanism of regulation of human renin mRNA. Genetic technologies and genomics research are an international priority likely to reap rich rewards intellectually and commercially. The shrinking of the once-touted gene number to a more modest level has been accompanied by a corresponding increase in the complexity in the protein products arising from each gene, and even more so the methods used by cells to control gene expression. By elucidating the latter for a key gene we will open up ....Molecular mechanism of regulation of human renin mRNA. Genetic technologies and genomics research are an international priority likely to reap rich rewards intellectually and commercially. The shrinking of the once-touted gene number to a more modest level has been accompanied by a corresponding increase in the complexity in the protein products arising from each gene, and even more so the methods used by cells to control gene expression. By elucidating the latter for a key gene we will open up new avenues for control of gene expression in various organisms. Devising novel means of chemically modulating stability of specific mRNA molecules will have beneficial implications for health, livestock production and agriculture.Read moreRead less
Diet, gut microbiota and the evolution of lifespan and reproduction. Nutrition has pronounced effects on lifespan and reproduction across animal species, yet how these effects are mediated is poorly understood. This project aims to determine if the gut microbiota regulates these nutritional effects. This project expects to deliver key insights on the complex interplay between nutrition and the gut microbiota, as well as the potential to manipulate this relationship to extend lifespan and alter r ....Diet, gut microbiota and the evolution of lifespan and reproduction. Nutrition has pronounced effects on lifespan and reproduction across animal species, yet how these effects are mediated is poorly understood. This project aims to determine if the gut microbiota regulates these nutritional effects. This project expects to deliver key insights on the complex interplay between nutrition and the gut microbiota, as well as the potential to manipulate this relationship to extend lifespan and alter reproduction. The expected outcomes of this project include generating new knowledge, building multidisciplinary collaborations and the development of novel experimental approaches. This should provide significant benefits, fore-most in bolstering Australia’s high international standing in evolutionary research. Read moreRead less
How evolution is constrained by trade-offs between the multiplication and survival of organisms. The negative correlation between reproduction (production of large numbers of progeny) and survival (resistance to external challenges) is a crucial trade-off that limits the evolution of perfect organisms. Such trade-offs are extremely difficult to study in closely controlled experiments because of the complexities in biological organisation and life-cycles. This project will explore trade-offs usin ....How evolution is constrained by trade-offs between the multiplication and survival of organisms. The negative correlation between reproduction (production of large numbers of progeny) and survival (resistance to external challenges) is a crucial trade-off that limits the evolution of perfect organisms. Such trade-offs are extremely difficult to study in closely controlled experiments because of the complexities in biological organisation and life-cycles. This project will explore trade-offs using a novel synthetic biology strategy. Genes in bacteria will be engineered to produce strains with a range of fixed but different trade-off settings. The strain sets will allow unprecedented analysis of reproduction-survival trade-offs and testing of important models of how trade-offs control fitness and evolutionary outcomes.Read moreRead less
ARC Centre for Kangaroo Genome. In this Australian-led Kangaroo Genome Project, we will map and characterize the tammar wallaby genome at the molecular level. Marsupial genomes are uniquely valuable because they provide comparisons that reveal new human genes, regulatory sequences and marsupial-specific genes. These will deliver new products and information useful for medicine, industry, agriculture and conservation. We will construct integrated genetic and physical maps of the genome, clone the ....ARC Centre for Kangaroo Genome. In this Australian-led Kangaroo Genome Project, we will map and characterize the tammar wallaby genome at the molecular level. Marsupial genomes are uniquely valuable because they provide comparisons that reveal new human genes, regulatory sequences and marsupial-specific genes. These will deliver new products and information useful for medicine, industry, agriculture and conservation. We will construct integrated genetic and physical maps of the genome, clone the whole genome as large inserts in BAC vectors, and build a "golden path" with minimal overlap. We will construct libraries of expressed genes from tammar tissues and array them for use in analysing gene expression.Read moreRead less