Genetic Models Of Cancer Development And Treatment
Funder
National Health and Medical Research Council
Funding Amount
$645,250.00
Summary
We are taking advantage of the powerful genetic tools in fruit flies to study the genetics of cancer. 72% of cancer genes are conserved between humans and fruit flies, making it a particularly suitable system. This project has two main aims: 1- to build tumours in fruit flies in an effort to understand better the individual genetic lesions that contribute to cancer It takes on average 4-7 mutations for a tumour to develop. While many genes associated with cancer have been identified, there are m ....We are taking advantage of the powerful genetic tools in fruit flies to study the genetics of cancer. 72% of cancer genes are conserved between humans and fruit flies, making it a particularly suitable system. This project has two main aims: 1- to build tumours in fruit flies in an effort to understand better the individual genetic lesions that contribute to cancer It takes on average 4-7 mutations for a tumour to develop. While many genes associated with cancer have been identified, there are many more that have not. What is more, it is still not clear precisely what mutations are responsible for a given tumour as tumours contain many genetic lesions most of which are incidental. We have a collection of fruit flies strains that represent various stages of the progress toward cancer development, and we intend to test different genetic combinations of these to determine which combinations result in cancer. 2- to identify a class of genes we have called 'oncogene suppressor genes' which may have the ability to prevent tumours from forming. Recently, it has been discovered that oncogenes may be required for both the INITIATION of tumours and the MAINTENANCE of tumours. This means that suppressing oncogene function may not only prevent tumour formation, but also tumour maintenance - in other words, it may make tumours go away. Thus, oncogene suppressor genes may represent exciting therapeutic targets for the treatment and possibly also prevention of cancer. At this time it is not clear whether oncogenes are generally required for tumour maintenance, or whether this is a property of only one or a few oncogenes. As these experiments are difficult and expensive to conduct in mammalian systems, we have devised simple, rapid tests in fruit flies instead. We plan to use these tests to investigate the effect of 'oncogene suppressor genes' on tumour initiation and maintenance in fruit flies. Ultimately, we believe these genes may represent therapeutic targets.Read moreRead less
Deciphering genome function in animal development. The normal development of an embryo depends on complex and finely tuned gene regulatory mechanisms. In this Fellowship, I will use sophisticated new technologies to discover which of our 30,000 genes is important for embryonic development, reveal the roles of these genes, and identify the control mechanisms that can go awry to cause birth defects. Our research will suggest new ways to diagnose and deal with these conditions, and will be applicab ....Deciphering genome function in animal development. The normal development of an embryo depends on complex and finely tuned gene regulatory mechanisms. In this Fellowship, I will use sophisticated new technologies to discover which of our 30,000 genes is important for embryonic development, reveal the roles of these genes, and identify the control mechanisms that can go awry to cause birth defects. Our research will suggest new ways to diagnose and deal with these conditions, and will be applicable to stem cell technologies, tissue regeneration, cancer biology, conservation, pest management and livestock breeding, thus delivering significant economic and social benefits to Australia. Read moreRead less
Olfactory signal transduction in Drosophila melanogaster. This project will strengthen Australia's research capabilities in the areas of molecular neurobiology and neurogenetics. The project will equip students with the intellectual and technical skills needed to work in priority areas such as genomics and biotechnology, as well as in medical and agricultural research, and education. The research has possible long term applications in modifying the behaviour of insects of agricultural or medical ....Olfactory signal transduction in Drosophila melanogaster. This project will strengthen Australia's research capabilities in the areas of molecular neurobiology and neurogenetics. The project will equip students with the intellectual and technical skills needed to work in priority areas such as genomics and biotechnology, as well as in medical and agricultural research, and education. The research has possible long term applications in modifying the behaviour of insects of agricultural or medical importance. For example, by inhibiting the ability of insects to perceive specific odours it may ultimately be possible to prevent insects that carry disease from identifying target animals, or plant pests from locating their host plants.Read moreRead less
Olfactory signalling and coding in Drosophila and other insects. Animals rely on olfactory cues to detect food, danger, and others of the same species. The olfactory systems of Drosophila and other insects are simpler than those of mammals, yet complex enough to offer fascinating systems for studying neural information processing. This project aims to investigate the role of the Drosophila odorant receptors in olfactory coding, and to use multiple approaches to isolate components of the poorly u ....Olfactory signalling and coding in Drosophila and other insects. Animals rely on olfactory cues to detect food, danger, and others of the same species. The olfactory systems of Drosophila and other insects are simpler than those of mammals, yet complex enough to offer fascinating systems for studying neural information processing. This project aims to investigate the role of the Drosophila odorant receptors in olfactory coding, and to use multiple approaches to isolate components of the poorly understood insect olfactory signal transduction pathway. In addition, the role of the NO/cGMP pathway in olfactory signalling will be studied using an olfactory mutant that has nitric oxide synthase defects.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE0561030
Funder
Australian Research Council
Funding Amount
$441,100.00
Summary
Developmental Imaging Facility. This application seeks to establish a facility to undertake expression profiling in vertebrate tissues on a genomic scale and at the highest resolution. Undertaking large scale projects of this nature requires specialised robotics and dedicated infrastructure for microscopy and tissue preparation. This facility will be the first of its type in Australia will permit researchers to perform genomic scale in situ screens, many as part of large international initiative ....Developmental Imaging Facility. This application seeks to establish a facility to undertake expression profiling in vertebrate tissues on a genomic scale and at the highest resolution. Undertaking large scale projects of this nature requires specialised robotics and dedicated infrastructure for microscopy and tissue preparation. This facility will be the first of its type in Australia will permit researchers to perform genomic scale in situ screens, many as part of large international initiatives in developmental and cellular biology. This large-scale, high-resolution expression profiling infrastructure is required to maintain international competitiveness and will dramatically improve our gene discovery, functional assessment and understanding of vertebrate development.Read moreRead less
Function and redundancy of SOX genes in the mammalian sex determination pathway. We are studying a mouse model of abnormal sex organ development in which genetically female mice develop as males. Our basic research program will lead to greater understanding of the genetic switch controlling the formation of male and female characteristics. This research should in turn provide insight into the causes of defects in patients with disorders of sex development, helping to inform the difficult clinica ....Function and redundancy of SOX genes in the mammalian sex determination pathway. We are studying a mouse model of abnormal sex organ development in which genetically female mice develop as males. Our basic research program will lead to greater understanding of the genetic switch controlling the formation of male and female characteristics. This research should in turn provide insight into the causes of defects in patients with disorders of sex development, helping to inform the difficult clinical decisions that need to be made for their treatment, and ultimately leading to better management and therapeutic strategies. Our studies may also provide unique methods to control the exotic mouse population, using the daughterless strategy.Read moreRead less
ARC Centre of Excellence in Biotechnology and Development. The Centre will create a multidisciplinary research team focusing on the molecular mechanisms that drive the specification and differentiation of male germ cells. This research will improve our fundamental understanding of how complex regulatory networks control the expression of a complex phenotype, the spermatozoon. It will also create a platform of knowledge from which we can stimulate the growth of the Australian Biotechnology indust ....ARC Centre of Excellence in Biotechnology and Development. The Centre will create a multidisciplinary research team focusing on the molecular mechanisms that drive the specification and differentiation of male germ cells. This research will improve our fundamental understanding of how complex regulatory networks control the expression of a complex phenotype, the spermatozoon. It will also create a platform of knowledge from which we can stimulate the growth of the Australian Biotechnology industry, the protection of the Australian Environment and the well-being of the Australian people. Key issues for this Centre include testicular cancer, male infertility, contraception, pest animal control, environmental impacts on human health and gene pharming.Read moreRead less
Genetic regulation of wing reduction in the emu. This project aims to examine the genetic mechanisms that generate limb diversity, using wing reduction in the emu as a model. A hot topic in biology at present is evolutionary developmental biology, or how genes control morphological diversity. This project will explore the functions of two novel genes implicated in wing reduction. The project expects to expand knowledge in the area of developmental biology, and limb morphogenesis specifically. It ....Genetic regulation of wing reduction in the emu. This project aims to examine the genetic mechanisms that generate limb diversity, using wing reduction in the emu as a model. A hot topic in biology at present is evolutionary developmental biology, or how genes control morphological diversity. This project will explore the functions of two novel genes implicated in wing reduction. The project expects to expand knowledge in the area of developmental biology, and limb morphogenesis specifically. It will bear upon the phylogeny of flightlessness among birds. It also has potential implications for studying human limb deformities. Overall, the project will enhance our understanding of how genes control the great diversity that we see in nature.Read moreRead less
Morphological development of the kidney – a paradigm for organogenesis. This project aims to shed new light on how the kidney develops, how normal adult function is established and how congenital kidney malformations occur. It aims to investigate a mathematical pattern that has been discovered in the program of branching morphogenesis which dictates kidney development. By combining cutting-edge genetic approaches, morphological analysis and mathematical modelling, this project plans to explore h ....Morphological development of the kidney – a paradigm for organogenesis. This project aims to shed new light on how the kidney develops, how normal adult function is established and how congenital kidney malformations occur. It aims to investigate a mathematical pattern that has been discovered in the program of branching morphogenesis which dictates kidney development. By combining cutting-edge genetic approaches, morphological analysis and mathematical modelling, this project plans to explore how this pattern is established, how it dictates kidney development and whether it constitutes an ancient mechanism central to organ formation. Project outcomes may improve understanding of fundamental developmental processes and developmental disease and variation. Project findings may also be important for understanding the development of other organ systems.Read moreRead less