Detection Of Alternative Lengthening Of Telomeres In The Mouse
Funder
National Health and Medical Research Council
Funding Amount
$471,000.00
Summary
In each cell, DNA is packaged into units called chromosomes, the ends of which (i.e., telomeres) become slightly shorter every time they are replicated during the production of new cells. Continued cell replication and hence continued telomere shortening eventually results in the inability of cells to replicate themselves any further. Normal cells have mechanisms to slow down, but not completely prevent telomere shortening. The development of a cancer depends on its cells being able to replicate ....In each cell, DNA is packaged into units called chromosomes, the ends of which (i.e., telomeres) become slightly shorter every time they are replicated during the production of new cells. Continued cell replication and hence continued telomere shortening eventually results in the inability of cells to replicate themselves any further. Normal cells have mechanisms to slow down, but not completely prevent telomere shortening. The development of a cancer depends on its cells being able to replicate themselves many times, and therefore they need to find a method to prevent their telomeres shortening. We discovered one such method, called Alternative Lengthening of Telomeres (ALT), that is used by some cancers. It has been shown in principle that cancer cells can be killed by disrupting their ability to prevent telomere shortening. Therefore, in another project we are developing methods needed to find drugs that inhibit ALT. In the meantime, we have found the first evidence that some normal cells have an ALT-like mechanism. Our speculation is that cancer cells are able to dysregulate and subvert this normal mechanism in order to prevent their telomeres from shortening. In this project, we will analyse the ALT-like mechanism in mice, to determine its characteristics, and to determine what tissues use it. This information will provide critically important insights into the ALT mechanism itself, and the likely side effects of drugs that inhibit ALT.Read moreRead less
Molecular Genetics Of The Host Response Defect In Cystic Fibrosis
Funder
National Health and Medical Research Council
Funding Amount
$564,690.00
Summary
Cystic fibrosis is the most common lethal genetic disease in Caucasian populations. Affected individuals suffer from a number of symptoms but the most serious is a chronic infect with the bacterial pathogen Pseudomonas aeruginosa. The sustained lung inflammation caused by infection with Pseudomonas aeruginosa ultimately destroys the structure of the lung to the point where it can no longer function. Gene therapy has been suggested as a possible treatment for the disease but another approach is t ....Cystic fibrosis is the most common lethal genetic disease in Caucasian populations. Affected individuals suffer from a number of symptoms but the most serious is a chronic infect with the bacterial pathogen Pseudomonas aeruginosa. The sustained lung inflammation caused by infection with Pseudomonas aeruginosa ultimately destroys the structure of the lung to the point where it can no longer function. Gene therapy has been suggested as a possible treatment for the disease but another approach is to identify the CF specific aspects of the inflammatory response and target those for therapeutic development. In our previous work we have identified several strong candidates for the inflammatory molecules in the CF lung and in this application we will test those candidates to see whether they play a major role in CF lung disease.Read moreRead less
Perceptual suppression mechanisms in the Drosophila brain. This project will investigate common processes underlying three means to losing conscious perception: selective attention, sleep and general anaesthesia. By studying these suppression mechanisms in a genetic model, the fly Drosophila melanogaster, fundamental processes will be highlighted that are required in the brain for maintaining perception in general.
Evolutionary analyses of short-read sequences from pooled samples. This project aims to provide biologists with a means of making sound, statistical inferences about evolution by using next-generation data from mixed samples. When biologists make statements about history, they use evolutionary trees, frequently reconstructed from the genetic data of many individuals. Next-generation sequencing provides large amounts of genetic data at low cost, but biologists have difficulty using these data for ....Evolutionary analyses of short-read sequences from pooled samples. This project aims to provide biologists with a means of making sound, statistical inferences about evolution by using next-generation data from mixed samples. When biologists make statements about history, they use evolutionary trees, frequently reconstructed from the genetic data of many individuals. Next-generation sequencing provides large amounts of genetic data at low cost, but biologists have difficulty using these data for evolutionary research, particularly when they sample mixtures of DNA from many individuals. The anticipated value of this project is that it allows evolutionary biologists to capitalise on the benefits of next-generation sequencing, without sacrificing their ability to make reliable inferences about history.Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE140101962
Funder
Australian Research Council
Funding Amount
$395,220.00
Summary
Functional epigenomics interrogation of DNA methylation dynamics during vertebrate development and evolution. DNA methylation (mC) is an epigenetic signal essential for the maintenance of correct gene expression patterns. To investigate the causal relationships between mC and transcription during vertebrate embryonic development and evolution, this project will perform high-resolution mC profiling at different stages of teleost, amphibian and mammalian development. Highly conserved and syntenic, ....Functional epigenomics interrogation of DNA methylation dynamics during vertebrate development and evolution. DNA methylation (mC) is an epigenetic signal essential for the maintenance of correct gene expression patterns. To investigate the causal relationships between mC and transcription during vertebrate embryonic development and evolution, this project will perform high-resolution mC profiling at different stages of teleost, amphibian and mammalian development. Highly conserved and syntenic, methylated sequences will then be used as baits in proteomics screens to identify novel 5mC 'readers'. The generation of genomic profiles of mC 'readers' and their integration with developmental mC maps will reveal transient epigenome dynamics during vertebrate embryogenesis and provide new insights into the conservation of these crucial developmental mechanisms.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE140100114
Funder
Australian Research Council
Funding Amount
$560,000.00
Summary
High Throughput Cell Genomics Centre. High throughput cell genomics centre: This project will establish a high throughput cell genomics centre comprising a Fluidigm C1™ Single-Cell AutoPrep and BioMark™ HD system providing researchers with the most innovative approach to single cell and small population analyses. The instruments will enable the unique capability to conduct single cell transcriptome analysis and high throughput gene expression, SNP genotyping and copy number variation analysis as ....High Throughput Cell Genomics Centre. High throughput cell genomics centre: This project will establish a high throughput cell genomics centre comprising a Fluidigm C1™ Single-Cell AutoPrep and BioMark™ HD system providing researchers with the most innovative approach to single cell and small population analyses. The instruments will enable the unique capability to conduct single cell transcriptome analysis and high throughput gene expression, SNP genotyping and copy number variation analysis as well as validation of next generation sequencing data. The information generated is crucial to advancing knowledge in important research fields including infection and immunity, regenerative medicine, immune responses, biomarker discovery, drug discovery, biotechnology and agriculture.Read moreRead less
Unique epigenetic states in plant stem cell niches for safeguarding genome integrity. Plant stem cells are the foundation cells of all plant growth and development, including generation of the reproductive cells. Therefore, it is critical that stem cells defend against attacks that may damage the genome. A unique epigenetic state in plant stem cell niches has been discovered that may protect the genome from damage due to parasitic DNA elements. Using sophisticated genomics, genetics, and cellula ....Unique epigenetic states in plant stem cell niches for safeguarding genome integrity. Plant stem cells are the foundation cells of all plant growth and development, including generation of the reproductive cells. Therefore, it is critical that stem cells defend against attacks that may damage the genome. A unique epigenetic state in plant stem cell niches has been discovered that may protect the genome from damage due to parasitic DNA elements. Using sophisticated genomics, genetics, and cellular technologies, this project will investigate how stem cell epigenetic state is linked to genome defence, how environmental stresses can disrupt the defence system, and the role of the system in driving new genetic diversity. This knowledge is of high importance as agricultural crops enter an era of increasingly challenging conditions.Read moreRead less
Charting the human epi-transcriptome. This project aims to use Oxford nanopore technologies and phage display technologies, to obtain quantitative, single-nucleotide resolution maps for any RNA modification of choice. This will allow systematic mapping of RNA modifications for which we currently lack transcriptome-wide maps, as well as investigate the roles, regulation and impact of RNA modifications in proper cellular functioning and cell differentiation. The project will provide significant be ....Charting the human epi-transcriptome. This project aims to use Oxford nanopore technologies and phage display technologies, to obtain quantitative, single-nucleotide resolution maps for any RNA modification of choice. This will allow systematic mapping of RNA modifications for which we currently lack transcriptome-wide maps, as well as investigate the roles, regulation and impact of RNA modifications in proper cellular functioning and cell differentiation. The project will provide significant benefits, such as to the economy by offering a cost-effective alternative to sequencing methods currently used to map DNA and RNA modifications.Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE150100091
Funder
Australian Research Council
Funding Amount
$341,000.00
Summary
Traffic on DNA: interplay between RNA polymerases and DNA-bound proteins. The DNA inside the cell is not just a repository of information, but is an active player in how that information is used. Proteins bind to defined locations on the DNA to control which genes are active, and genes are expressed by RNA polymerases that track along the DNA. Collisions between RNA polymerases and DNA-bound proteins can remove the proteins or block the polymerase. How can these essential processes safely coexis ....Traffic on DNA: interplay between RNA polymerases and DNA-bound proteins. The DNA inside the cell is not just a repository of information, but is an active player in how that information is used. Proteins bind to defined locations on the DNA to control which genes are active, and genes are expressed by RNA polymerases that track along the DNA. Collisions between RNA polymerases and DNA-bound proteins can remove the proteins or block the polymerase. How can these essential processes safely coexist on the DNA? The project aims to integrate systematic experiments using well-defined genetic components and mathematical modelling to understand the 'design' features of DNA and proteins that minimise these traffic problems. A better understanding could inform new strategies for manipulation of gene expression.Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE210101235
Funder
Australian Research Council
Funding Amount
$424,500.00
Summary
Encounters with hominins: the history of human arrival in Sahul. This project aims to provide a detailed understanding on the remarkably complex encounters between archaic and modern human populations in Island Southeast Asia, New Guinea and Australia during the Pleistocene. The project plans to provide the largest collection of human genetic diversity from this vast geographical region and significantly advance current knowledge on one of the most intriguing questions in human evolution. These ....Encounters with hominins: the history of human arrival in Sahul. This project aims to provide a detailed understanding on the remarkably complex encounters between archaic and modern human populations in Island Southeast Asia, New Guinea and Australia during the Pleistocene. The project plans to provide the largest collection of human genetic diversity from this vast geographical region and significantly advance current knowledge on one of the most intriguing questions in human evolution. These insights are expected to bring important social and cultural benefits for Australia by unveiling the singularly deep genetic history of Aboriginal Australians, including their ancient connection to indigenous communities from Indonesia and New Guinea that extends back to when people first arrived in Australia.
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