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
Group orbits in garmonic analysis and ergodic theory. Researchers from many areas need a type of mathematical analysis which involves the behaviour of a system - which may be a set of data points - under repeated application of some operation or group of operations. The structures arising from this kind of process are known as group orbits. The project gives information about their nature. Two major types of orbits are considered, coming from actions of discrete groups on measure spaces, and fro ....Group orbits in garmonic analysis and ergodic theory. Researchers from many areas need a type of mathematical analysis which involves the behaviour of a system - which may be a set of data points - under repeated application of some operation or group of operations. The structures arising from this kind of process are known as group orbits. The project gives information about their nature. Two major types of orbits are considered, coming from actions of discrete groups on measure spaces, and from smooth actions of Lie groups on manifolds, where powerful geometric methods are available. The project will yield new understandings of entropy, and new approaches to Fourier analysis.Read moreRead less
Ergodic theory and number theory. Recent advances in the theory of measured dynamical systems investigated by the proponents include new versions of entropy, and the study of spectral theory for non-singular systems. These will be further developed in this joint project with the French CNRS. The results are expected to have interesting applications in physics and number theory.
Entropy and maximal entropy in Markov systems. Entropy is a measure of how well-ordered a system is: chaotic systems have high entropy. Two approaches to entropy are available, via the limiting behaviour of the orbits of points, which yields topological entropy, and via the behaviour of the distributions of measures of partitions, yielding measure-theoretic entropy. The topological entropy is the least upper bound of entropies of all possible measures. We study when there is a measure which real ....Entropy and maximal entropy in Markov systems. Entropy is a measure of how well-ordered a system is: chaotic systems have high entropy. Two approaches to entropy are available, via the limiting behaviour of the orbits of points, which yields topological entropy, and via the behaviour of the distributions of measures of partitions, yielding measure-theoretic entropy. The topological entropy is the least upper bound of entropies of all possible measures. We study when there is a measure which realises this bound, describing the structure of such systems via Markov and Bratteli diagrams. Our methods will be applied to new versions of entropy for non-singular systems. This will assist in the description of chaotic behaviour.Read moreRead less
Symmetries in analysis. Technical research is like an iceberg. The 10% you see in applications is supported by 90% hidden, long-term, sometimes abstruse or theoretical-sounding work. The area of mathematical analysis has, for over 200 years, proved its worth as part of the unseen 90%, giving us such important tools as Fourier analysis, statistical mechanics and quantum mechanics. Australia is known as a world leader in mathematical analysis, and it is important for the country to maintain that e ....Symmetries in analysis. Technical research is like an iceberg. The 10% you see in applications is supported by 90% hidden, long-term, sometimes abstruse or theoretical-sounding work. The area of mathematical analysis has, for over 200 years, proved its worth as part of the unseen 90%, giving us such important tools as Fourier analysis, statistical mechanics and quantum mechanics. Australia is known as a world leader in mathematical analysis, and it is important for the country to maintain that edge in a number of key disciplines, so we can continue to participate in global technological advance. The project has an international focus which will enable that to happen. It will also provide training for the next generation of mathematicians. Read moreRead less