Evolutionary algorithms for problems in functional genomics data analysis. Skin cancer has a high incidence in the Australian population. Schizophrenia is a psychiatric disorder that affects a significant proportion of the population worldwide. Both illnesses have genetic roots and can be triggered by environmental factors. We will uncover genetic relationship to disease and their responses to environmental conditions using computational methods and mathematical algorithms that can aid in the de ....Evolutionary algorithms for problems in functional genomics data analysis. Skin cancer has a high incidence in the Australian population. Schizophrenia is a psychiatric disorder that affects a significant proportion of the population worldwide. Both illnesses have genetic roots and can be triggered by environmental factors. We will uncover genetic relationship to disease and their responses to environmental conditions using computational methods and mathematical algorithms that can aid in the determination of function, especially in disease states. Understanding the complex genetic interactions that trigger these illnesses would give great benefits in preventive health care, skin cancer and schizophrenia genetic basis, and may lay the ground for building new methods for "personalized medicine".
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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
Mechanisms of Recovery after Extinction of Conditioned Behaviour. Old habits die hard and may never die at all. My previous ARC-funded research has revealed that extinguished learning can be recovered rapidly and in unsuspected ways. This project is aimed at building a neural network to explain how old learning can recovered. In practical terms, rapid recovery has both benefits, e.g., our ability to regain old skills with brief refresher training, and costs, e.g., relapse after therapies for anx ....Mechanisms of Recovery after Extinction of Conditioned Behaviour. Old habits die hard and may never die at all. My previous ARC-funded research has revealed that extinguished learning can be recovered rapidly and in unsuspected ways. This project is aimed at building a neural network to explain how old learning can recovered. In practical terms, rapid recovery has both benefits, e.g., our ability to regain old skills with brief refresher training, and costs, e.g., relapse after therapies for anxiety disorders and substance abuse. In theoretical terms, understanding recovery in biological systems will inform research concerning both the neural basis of memory and the design of robots.Read moreRead less
Design of dynamic visual signals. Models of the design of visual signals depend heavily upon analyses of static ornaments. Nothing is known about dynamic visual signals. We will use an array of new techniques to tackle this problem for the first time. Motion analyses will define the task faced by the visual system. Sensory limitations will be measured to identify constraints on signal evolution. Digital video playback studies will assess recognition and explain aspects of signal design. Results ....Design of dynamic visual signals. Models of the design of visual signals depend heavily upon analyses of static ornaments. Nothing is known about dynamic visual signals. We will use an array of new techniques to tackle this problem for the first time. Motion analyses will define the task faced by the visual system. Sensory limitations will be measured to identify constraints on signal evolution. Digital video playback studies will assess recognition and explain aspects of signal design. Results will test the generality of principles that have been developed in studies of female mate choice and extend these ideas to address intra-sexual selection operating through opponent assessment.Read moreRead less
Epigenetic silencing in vertebrates: evolution and function from the bottom-up. The primary benefits are contribution to Australia's knowledge base and raising the profile of functional genomics in Australia, with the research priority of Frontier Technologies for Building and Transforming Australian Industries and priority goals in Breakthrough Science and Frontier Technologies. This project focuses on important biological questions surrounding gene regulation and sex chromosome evolution. Inte ....Epigenetic silencing in vertebrates: evolution and function from the bottom-up. The primary benefits are contribution to Australia's knowledge base and raising the profile of functional genomics in Australia, with the research priority of Frontier Technologies for Building and Transforming Australian Industries and priority goals in Breakthrough Science and Frontier Technologies. This project focuses on important biological questions surrounding gene regulation and sex chromosome evolution. International attention has already resulted in genome characterization of Australian icons (wallaby, Tasmanian devil and platypus), more research on these, and other Australian animals, will further highlight the importance of Australian fauna and impact positively on our scientific profile.Read moreRead less
Structure and function of a new class of multi-zinc finger (MZF) transcriptional regulators. An understanding of how genes are switched on and off during the development and lifetime of an organism is central to developing the ability to fight many diseases in a rational way. This project will advance our knowledge in this area at a fundamental molecular level by examining the mechanisms through which a specific set of proteins controls gene expression.