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
Alternative Splicing in the Mouse Transcriptome. Although the human genome completion is cause for excitement we do not have any firm indication of precisely how many protein-coding genes exist in a mammalian genome. We have even less indication of the extent to which these genes generate alternative gene products, through a process termed alternative splicing. The detection and sequencing of these full-length alternative gene products is the focus of this application. This application details t ....Alternative Splicing in the Mouse Transcriptome. Although the human genome completion is cause for excitement we do not have any firm indication of precisely how many protein-coding genes exist in a mammalian genome. We have even less indication of the extent to which these genes generate alternative gene products, through a process termed alternative splicing. The detection and sequencing of these full-length alternative gene products is the focus of this application. This application details the opportunity to participate in the identification of the full transcriptome of the mouse and is part of a collaborative effort with The RIKEN Genome Sciences Center in Japan.Read moreRead less
A powerful new genetic view of the recent evolutionary history of humans and their diseases. Bacteria on teeth cause dental disease, but have also recently been associated with broader health issues, including diabetes, stroke and heart issues. In this project ancient DNA will be used to reveal changes in these bacteria as humans moved from a hunter-gatherer to farming lifestyle, providing valuable background information for modern dental/medical practice.
Statistical methods for detection of non-coding RNAs in eukaryote genomes. Understanding how eukaryotic cells work is a major goal of 21st century biology. A crucial step will be to catalogue the functional components of eukaryotic genomes. Australian researchers must be involved in this process at an early stage, in order to maximise commercial opportunities, attract quality researchers and position ourselves for further advances. This project will make major contributions to international effo ....Statistical methods for detection of non-coding RNAs in eukaryote genomes. Understanding how eukaryotic cells work is a major goal of 21st century biology. A crucial step will be to catalogue the functional components of eukaryotic genomes. Australian researchers must be involved in this process at an early stage, in order to maximise commercial opportunities, attract quality researchers and position ourselves for further advances. This project will make major contributions to international efforts in this area, via the development of statistical methods for segmenting genomes, classification of those segments, and study of the resulting classes. In the long term, enhanced understanding of eukaryotic cells will lead to breakthroughs in biology, and to medical, pharmaceutical, agricultural and scientific advances.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
Sex and bottlenecks: understanding the evolutionary dynamics of bacterial adaptation. Bacteria can rapidly adapt to changing environments, often with devastating consequences for humans. However, this adaptive evolution is often limited by strong reductions in population size, in particular during transmission from one host to another. This project aims to investigate whether recombination in bacteria can overcome the limits that such bottlenecks impose on the rate of adaptation. To this end, it ....Sex and bottlenecks: understanding the evolutionary dynamics of bacterial adaptation. Bacteria can rapidly adapt to changing environments, often with devastating consequences for humans. However, this adaptive evolution is often limited by strong reductions in population size, in particular during transmission from one host to another. This project aims to investigate whether recombination in bacteria can overcome the limits that such bottlenecks impose on the rate of adaptation. To this end, it will construct mathematical models and complement them with evolution experiments in bacterial populations. Results from this research aim to generate fundamental insights into the role of recombination in bacterial evolution and will provide guidance for developing management strategies for bacterial pathogens.Read moreRead less
Predicting the evolutionary dynamics of adaptation. This project aims to address the question of how we can predict adaptive evolution. The project aims to probe the limits of evolutionary predictions by using a model system of bacterial populations that adapt to the presence of multiple stressors. This will be combined with high-throughput fitness measurements, whole genome sequencing and computer simulations. Anticipated outcomes include novel insights into deep questions regarding the structu ....Predicting the evolutionary dynamics of adaptation. This project aims to address the question of how we can predict adaptive evolution. The project aims to probe the limits of evolutionary predictions by using a model system of bacterial populations that adapt to the presence of multiple stressors. This will be combined with high-throughput fitness measurements, whole genome sequencing and computer simulations. Anticipated outcomes include novel insights into deep questions regarding the structure of fitness landscapes and the repeatability, predictability and contingency of adaptive evolution. The project is expected to provide significant benefits, informing the development of improved strategies for managing pathogen resistance to antimicrobial drugs.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
Genetic dissection of a regulatory deubiquitlyation network. The potential impact of this work is widespread, because although it is known that ubiquitlyation has regulatory consequences in multicellular eukaryotes, individual networks have not been completely described in higher eukaryotes. Knowledge gained about fundamental processes in the A. nidulans model system is directly applicable to fungi used in biotechnology in the food, beverage, enzyme and pharmaceutical production industries, and ....Genetic dissection of a regulatory deubiquitlyation network. The potential impact of this work is widespread, because although it is known that ubiquitlyation has regulatory consequences in multicellular eukaryotes, individual networks have not been completely described in higher eukaryotes. Knowledge gained about fundamental processes in the A. nidulans model system is directly applicable to fungi used in biotechnology in the food, beverage, enzyme and pharmaceutical production industries, and to fungal pathogens. Since the fungal genes that form the basis of this project are conserved in higher eukaryotes including humans, the knowledge will be transferable to these systems. A further benefit that cannot be overstated is the research education and training opportunities provided.
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