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
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
Mutagenesis and combinatorial algorithms for sequencing problematic genomic regions. This project will develop a remarkable and original approach to DNA sequencing with potential to radically improve the speed, accuracy and effectiveness of existing sequencing technologies. It is especially useful for dealing with difficult-to-sequence genomic regions and has implications for all sequencing projects, including completion of the Human Genome Project. The approach involves generating, and wholly o ....Mutagenesis and combinatorial algorithms for sequencing problematic genomic regions. This project will develop a remarkable and original approach to DNA sequencing with potential to radically improve the speed, accuracy and effectiveness of existing sequencing technologies. It is especially useful for dealing with difficult-to-sequence genomic regions and has implications for all sequencing projects, including completion of the Human Genome Project. The approach involves generating, and wholly or partially sequencing, mutated copies of problematic regions of the target genome. Advanced combinatorial algorithms are then used to form highly probable alignments between strings and determine the unknown sequence. The approach has additional benefits in detecting single-nucleotide polymorphisms and sequencing errors.Read moreRead less
Morphological development of the kidney – a paradigm for organogenesis. This project aims to shed new light on how the kidney develops, how normal adult function is established and how congenital kidney malformations occur. It aims to investigate a mathematical pattern that has been discovered in the program of branching morphogenesis which dictates kidney development. By combining cutting-edge genetic approaches, morphological analysis and mathematical modelling, this project plans to explore h ....Morphological development of the kidney – a paradigm for organogenesis. This project aims to shed new light on how the kidney develops, how normal adult function is established and how congenital kidney malformations occur. It aims to investigate a mathematical pattern that has been discovered in the program of branching morphogenesis which dictates kidney development. By combining cutting-edge genetic approaches, morphological analysis and mathematical modelling, this project plans to explore how this pattern is established, how it dictates kidney development and whether it constitutes an ancient mechanism central to organ formation. Project outcomes may improve understanding of fundamental developmental processes and developmental disease and variation. Project findings may also be important for understanding the development of other organ systems.Read moreRead less
The structure and patterning of branching morphogenesis in the developing kidney. This project aims to understand a fundamental developmental process known as branching morphogenesis, which drives the formation of many organs including the kidney, lungs and glands. Understanding this process will be of key importance in understand how our organs form.
A paradigm of genomic discovery - an investigation of the allelic architecture of height. Understanding the complexities of the human body from its DNA sequence has proven difficult. Genomic discovery is best developed using stable, easily measurable and highly heritable characteristics such as height. By taking advantage of 2 large population surveys of adult and adolescent stature we shall apply modern molecular techniques and statistical strategies to identify and characterise the exact chang ....A paradigm of genomic discovery - an investigation of the allelic architecture of height. Understanding the complexities of the human body from its DNA sequence has proven difficult. Genomic discovery is best developed using stable, easily measurable and highly heritable characteristics such as height. By taking advantage of 2 large population surveys of adult and adolescent stature we shall apply modern molecular techniques and statistical strategies to identify and characterise the exact changes in DNA that determine height. This work builds on substantial preliminary leads from unique resources and complementary expertise in the scientific specialties. The results from this work will inform other genomic research and provide information about growth and bone biology.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
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