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
Deciphering the genetic architecture of human complex traits. This project aims to develop statistical methods to integrate data from genetic studies of complex traits such as stature and cognition. Molecular phenotypes such as gene expression in large samples will be used to predict target genes and regulatory elements of those traits. Understanding the genetic basis of human complex traits is critical to longstanding questions in human and evolutionary biology. The project will also detect sig ....Deciphering the genetic architecture of human complex traits. This project aims to develop statistical methods to integrate data from genetic studies of complex traits such as stature and cognition. Molecular phenotypes such as gene expression in large samples will be used to predict target genes and regulatory elements of those traits. Understanding the genetic basis of human complex traits is critical to longstanding questions in human and evolutionary biology. The project will also detect signatures of natural selection in shaping the genetic variation in complex traits. The project will provide better understanding of complex traits in global populations and the history of human evolution, and will develop methods applicable in plant and animal contexts.Read moreRead less
Exploring genetic diversity to identify new heat tolerance genes in wheat. This project aims to improve the selection and development of heat-tolerant wheat varieties. Heatwaves seriously reduce wheat yields worldwide, and the situation will worsen with climate variation. This project aims to apply a broad genetic scan to identify the main chromosome regions controlling heat tolerance at the sensitive flowering stage in Australian and European wheat varieties. It is expected that this knowledge ....Exploring genetic diversity to identify new heat tolerance genes in wheat. This project aims to improve the selection and development of heat-tolerant wheat varieties. Heatwaves seriously reduce wheat yields worldwide, and the situation will worsen with climate variation. This project aims to apply a broad genetic scan to identify the main chromosome regions controlling heat tolerance at the sensitive flowering stage in Australian and European wheat varieties. It is expected that this knowledge will deliver crucial breeders’ tools to select heat-tolerant varieties. The project also aims to identify genes most likely to control tolerance at these chromosome locations using gene expression profiling data, trait associations and knowledge of heat-tolerance genes from other species. It is expected that these genes will reveal molecular mechanisms of heat tolerance and create new opportunities to engineer superior levels of tolerance in cereals.Read moreRead less
Genome-wide determination of Puccinia psidii s.l. rust resistance in eucalypts. Recently, guava rust was detected in Australia, posing significant risks to native flora, plantations, and timber exports. Scientists from The University of Melbourne and Victorian Department of Primary Industries together with tree breeders, forest growers and forest managers aim to use tree genomics rust resistance breeding to enable management and operational responses and inform policy development.
Fertility crisis: harnessing the genomic tension behind pollen fertility in sorghum. Hybrid sorghum varieties yield more grain than inbred varieties but the production seed for farmers can be difficult. This project will identify the genes responsible for a trait that makes hybrid seed production possible and this knowledge will help raise sorghum yields in Australian and in some of the world’s poorest countries.
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