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
Discovering genes and mechanisms regulating immune responses. The Fellowship will retain and expand a pioneering Australian research program, and attract to Australia major international investment and technology linkages, making use of the DNA sequence of humans and other mammals to advance understanding of immunity and infection control in public health, agriculture and industry. The program will build on Australia's pre-eminent research strengths in the field of immunity and infection, and w ....Discovering genes and mechanisms regulating immune responses. The Fellowship will retain and expand a pioneering Australian research program, and attract to Australia major international investment and technology linkages, making use of the DNA sequence of humans and other mammals to advance understanding of immunity and infection control in public health, agriculture and industry. The program will build on Australia's pre-eminent research strengths in the field of immunity and infection, and will create new knowledge and resources to improve human and animal health through vaccines, pharmaceuticals and public health policy. Read moreRead less
Genetic control of plant organ growth. Plants organs, such as leaves and petals, have a distinct size and shape reflecting differences in growth. Despite its importance, very little is known about the mechanisms that regulate growth. The objectives of this proposal are a) to test whether organ growth depends on cell-cell signalling and b) to identifying genes that regulate growth, and to characterize their molecular function.
Functions Of A Novel Conserved DNA Damage Response Protein Family In Telomere Stability
Funder
National Health and Medical Research Council
Funding Amount
$282,825.00
Summary
The free DNA ends of chromosomes, termed telomeres, generally resemble broken DNA. Because broken DNA is a major contributing factor to the onset of cancer, cells try to fix broken ends. However, in case of telomeres, such repair processes have to be prevented because otherwise different chromosomes would fuse with each other. Fused chromosomes are very fragile and cannot be evenly distributed between dividing cells, and are therefore another important trigger of cancer development. Therefore, c ....The free DNA ends of chromosomes, termed telomeres, generally resemble broken DNA. Because broken DNA is a major contributing factor to the onset of cancer, cells try to fix broken ends. However, in case of telomeres, such repair processes have to be prevented because otherwise different chromosomes would fuse with each other. Fused chromosomes are very fragile and cannot be evenly distributed between dividing cells, and are therefore another important trigger of cancer development. Therefore, chromosome ends are covered by a cap, which hides them from the DNA damage response machinery. From these considerations it is clear that there are close connections between the cellular DNA damage response and chromosome ends. Moreover, recently it has become clear that DNA damage proteins are also required to stop normal cells from growing, a process termed senescence. Senescence is a consequence of shortened chromosome ends, and does not occur in cancer cells. Altogether, it is clear that DNA breaks and senescence are two of the major questions for our understanding of cancer development. We have identified a novel conserved protein family that is involved in the response to DNA damage in yeast and humans. In addition, the yeast Mdt1 protein is a very sensitive indicator of changes in the telomere cap. Absence of proteins that organise the cap leads to the addition of several phosphate groups to the Mdt1 protein. We propose that phosphate-coupled Mdt1 prevents chromosome ends from fusion with each other, or from fusing with broken DNA ends after widespread damage. As a consequence, cells that have mild cap defects die at an >1000-fold increased rate in response to DNA damage when they also lack Mdt1. As part of this application we want to find out the precise mechanism by which Mdt1 stabilises chromosome ends, and test our hypothesis that the corresponding human protein termed ASCIZ also has similar functions in protecting chromosome ends.Read moreRead less
Developing DNA tracking methods to identify illegally logged timber products from Africa. Illegal logging causes societal and environmental forest degradation, and is a high priority for international control. This project will produce a range of DNA methods that allow the tracing of the geographic source of origin for timber products from African tropical forests that will allow producers and consumers to better market and choose their products.
Evolution, disease and extinction - using ancient and modern Deoxyribonucleic acid (DNA) to investigate molecular evolution in the Tasmanian devil. The Tasmanian devil is Australia's largest living marsupial carnivore and one of Tasmania's key tourism icons. Extinction in the wild will have long-term impacts on Tasmanian native ecosystems and economy. This study will provide critical genetic data and tools to monitor and prioritise conservation strategies, including insurance populations and dis ....Evolution, disease and extinction - using ancient and modern Deoxyribonucleic acid (DNA) to investigate molecular evolution in the Tasmanian devil. The Tasmanian devil is Australia's largest living marsupial carnivore and one of Tasmania's key tourism icons. Extinction in the wild will have long-term impacts on Tasmanian native ecosystems and economy. This study will provide critical genetic data and tools to monitor and prioritise conservation strategies, including insurance populations and disease suppression, aimed at preventing extinction. It will strengthen ongoing conservation programs carried out by the Save the Tasmanian Devil Program and will help publicise the plight of the devil both nationally and internationally.Read moreRead less
The roles of relatedness and reproductive success in complex social systems of dolphins. Theories of the role of genetic relatedness and reproductive success in mammalian social behaviour have mostly been restricted to primates and carnivores. Coexisting alternative strategies within one population of bottlenose dolphins (Shark Bay WA) offer unprecedented opportunities for such investigations. The male alliances? complexity is unparalleled outside humans, and may require new theory. Some femal ....The roles of relatedness and reproductive success in complex social systems of dolphins. Theories of the role of genetic relatedness and reproductive success in mammalian social behaviour have mostly been restricted to primates and carnivores. Coexisting alternative strategies within one population of bottlenose dolphins (Shark Bay WA) offer unprecedented opportunities for such investigations. The male alliances? complexity is unparalleled outside humans, and may require new theory. Some female lineages show tool-use - rare outside humans, and virtually unknown in marine species. Our behavioural and genetic database has exceptional size, detail and duration for marine mammals, and is most valuable if continued while known individuals' offspring reach a stage where they can be sampled.Read moreRead less
Understanding how cells compact and segregate DNA in vertebrates. How a cell compacts and divides its DNA is still a major unanswered question in biology. This project will determine the way in which a cell compacts its DNA nearly ten thousand fold to allow the faithful and accurate segregation to daughter nuclei.
Discovery Early Career Researcher Award - Grant ID: DE170100443
Funder
Australian Research Council
Funding Amount
$372,000.00
Summary
Landscape genomics to make an endangered community resilient. This project aims to use landscape genomic techniques to assess how key species of the critically endangered Box-Gum Grassy Woodland community migrate and adapt under changing environmental conditions. Changing climate and land use threaten ecological communities, and alter environments at alarming rates. When species are pushed beyond their environmental tolerances, they will migrate, adapt or face local extinction. This alteration o ....Landscape genomics to make an endangered community resilient. This project aims to use landscape genomic techniques to assess how key species of the critically endangered Box-Gum Grassy Woodland community migrate and adapt under changing environmental conditions. Changing climate and land use threaten ecological communities, and alter environments at alarming rates. When species are pushed beyond their environmental tolerances, they will migrate, adapt or face local extinction. This alteration of the community structure affects the stability and function of the ecosystem. Expected outcomes include efficient use of limited conservation resources, ensuring the long term persistence of the endangered community.Read moreRead less