The role of X-chromosome inactivation in quantitative trait variation. This project aims to develop methods and software that can be applied to genetic and genomic studies in animal breeding, wildlife protection, and humans. X-chromosome inactivation (XCI) is an important biological phenomenon but its effect on quantitative trait variation remains largely unknown. This project aims to develop novel statistical methods to estimate the X-linked genetic variance and the proportion that escapes XCI, ....The role of X-chromosome inactivation in quantitative trait variation. This project aims to develop methods and software that can be applied to genetic and genomic studies in animal breeding, wildlife protection, and humans. X-chromosome inactivation (XCI) is an important biological phenomenon but its effect on quantitative trait variation remains largely unknown. This project aims to develop novel statistical methods to estimate the X-linked genetic variance and the proportion that escapes XCI, and identify trait-associated genetic variants affected and not affected by XCI. The methods would then be applied to large datasets from genome-wide association studies for a large number of traits. Project outcomes may enable us to better understand the role of XCI in quantitative trait variation and gene expression in humans and animals.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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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
Estimation of non-additive genetic variance for complex traits using genome-wide single nucleotide polymorphyisms and sequence data. Finding genes for traits of importance in agriculture, ecology and human health depends on understanding the genetic basis of these traits. This project will investigate whether variation in traits in humans, cattle and wild sheep are influenced by gene-gene interactions.
The genetic architecture and evolution of quantitative traits. Most important traits are controlled by many genes and by the environment, however there is little knowledge of how many genes are involved in these complex traits and what their effects are. This project will describe the number of genes and their effects for complex traits in humans and livestock and explain how these genes evolve.
Rapid mapping of genes for complex traits. This project will develop a new resource that will allow rapid identification of genes controlling complex traits. This world-leading resource will improve knowledge of diseases like diabetes and neurological diseases.