A genetic analysis of the role of an atypical hexokinase in gene regulation. This project addresses a question which is relevant to all living things-how do changes in the environment of a cell bring about a change in gene expression? The aim of this project is to investigate the role of hexokinases in gene regulation by studying the Aspergillus nidulans xprF gene, which encodes an an unusual hexokinase. Hexokinases are thought to be the glucose sensors in plants, animals and fungi, and play a ....A genetic analysis of the role of an atypical hexokinase in gene regulation. This project addresses a question which is relevant to all living things-how do changes in the environment of a cell bring about a change in gene expression? The aim of this project is to investigate the role of hexokinases in gene regulation by studying the Aspergillus nidulans xprF gene, which encodes an an unusual hexokinase. Hexokinases are thought to be the glucose sensors in plants, animals and fungi, and play a role in the development of diabetes in humans. In plants, sugars affect many processes including growth, flowering, photosynthesis, nitrogen metabolism, starch synthesis, pigmentation and response to pathogens.Read moreRead less
Sexual antagonism and the consequences of sex-specific selection. Males and females arise from essentially the same genome yet are selected in vastly different ways. This exposes gene pools to alternate episodes of feminising- and masculinising-selection, thereby promoting Sexually Antagonistic (SA) evolution. Sex chromosomes are predicted to play an important role in SA evolution because sex-linkage allows for gender-specific gene expression, but data on the role of sex-linked genes are limited ....Sexual antagonism and the consequences of sex-specific selection. Males and females arise from essentially the same genome yet are selected in vastly different ways. This exposes gene pools to alternate episodes of feminising- and masculinising-selection, thereby promoting Sexually Antagonistic (SA) evolution. Sex chromosomes are predicted to play an important role in SA evolution because sex-linkage allows for gender-specific gene expression, but data on the role of sex-linked genes are limited to Drosophila, a male heterogametic (XY) model. This project will determine the consequences of SA selection in the butterfly Eurema hecabe (a female ZW heterogamete) using experimental evolution and the feminising endosymbiont Wolbachia to force male genomes through bouts of feminising selection.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
Evolution, selection and estimation of polygenic epistatic networks in quantitative traits. Traits observed in organisms, such as height, are the result of an individual's genes and how they relate to the environment. But genes do not act alone; they work together in complex interactions. This project aims to understand these interactions and their role in animal production and human disease.
The behaviour-genetics of NAPLAN data: Increasing power for complex analyses. This longitudinal behaviour-genetic study of the National Assessment Program – Literacy and Numeracy (NAPLAN) results at Grades 3, 5, 7 and 9 will continue to document the influence of genes and environmental factors on individual differences in school achievement. It aims to strengthen the longitudinal aspects of the data, allowing the project to identify sources of stability and change across the seven school years o ....The behaviour-genetics of NAPLAN data: Increasing power for complex analyses. This longitudinal behaviour-genetic study of the National Assessment Program – Literacy and Numeracy (NAPLAN) results at Grades 3, 5, 7 and 9 will continue to document the influence of genes and environmental factors on individual differences in school achievement. It aims to strengthen the longitudinal aspects of the data, allowing the project to identify sources of stability and change across the seven school years of the NAPLAN. It also aims to increase numbers in the low and high tails of the score distributions, creating a clearer picture of deficits like dyslexia and dyscalculia, and allow for firmer identification of gene-by-environment interactions. The project aims to further illuminate any differential effectiveness of schools and teachers on student outcomes, a topic of high public interest.Read moreRead less
Genetic variation of transcriptional control. Genetic variation is a key cause phenotype differences in humans, animals, and plants and so of great economic importance. Despite its proven importance to human diseases, ?quantitative? variation in the amount of gene expression rather than ?qualitative? protein sequence changes, has not been systematically studied. We have developed a powerful method to identify genetic causes of quantitative variation using crosses of inbred mice in conjunction wi ....Genetic variation of transcriptional control. Genetic variation is a key cause phenotype differences in humans, animals, and plants and so of great economic importance. Despite its proven importance to human diseases, ?quantitative? variation in the amount of gene expression rather than ?qualitative? protein sequence changes, has not been systematically studied. We have developed a powerful method to identify genetic causes of quantitative variation using crosses of inbred mice in conjunction with microarray techniques to analyse expression of thousands of genes simultaneously. These studies will be extended to humans and be significant to wide areas of biological and commercial activity.Read moreRead less