Drugging the undruggable: Development of novel technologies to selectively regulate the expression of targets driving cancer and other diseases. Transcription factors are “undruggable” targets playing a principal role driving cancer. This project will create novel therapeutic strategies to inhibit transcription factors and other elusive targets differentially expressed in diseased cells, without affecting normal tissue. It proposes to construct engineered proteins able to bind and modify specifi ....Drugging the undruggable: Development of novel technologies to selectively regulate the expression of targets driving cancer and other diseases. Transcription factors are “undruggable” targets playing a principal role driving cancer. This project will create novel therapeutic strategies to inhibit transcription factors and other elusive targets differentially expressed in diseased cells, without affecting normal tissue. It proposes to construct engineered proteins able to bind and modify specific key genes deregulated in cancer, to correct their expression and stably reprogram the phenotype of the tumour cell in a normal-like state. It outlines the engineering of novel synthetic agents to block specific protein-protein interactions in cancer cells and to induce potent tumour cell death. This work will generate novel and selective therapeutics to treat un-curable forms of tumours.Read moreRead less
Comprehensive characterisation of DNA demethylation pathways in vivo. This project aims to provide a better understanding of the roles that DNA methylation plays during embryonic development. DNA methylation is a major regulatory mark present in vertebrate genomes. It is well established that the genomic patterns of DNA methylation are being actively remodelled during vertebrate embryogenesis. Nevertheless, it remains unclear how these events impact gene regulation and embryonic development itse ....Comprehensive characterisation of DNA demethylation pathways in vivo. This project aims to provide a better understanding of the roles that DNA methylation plays during embryonic development. DNA methylation is a major regulatory mark present in vertebrate genomes. It is well established that the genomic patterns of DNA methylation are being actively remodelled during vertebrate embryogenesis. Nevertheless, it remains unclear how these events impact gene regulation and embryonic development itself. This project expects to unravel the functional contributions of DNA methylation to vertebrate embryogenesis by using latest cutting-edge genomics techniques. The project will be carried out on the highly tractable zebrafish model system which allows for easy genetic manipulation of the desired sequences. This project aims to provide a better understanding of embryonic development of vertebrates, including humans.Read moreRead less
Towards a new understanding of the reproductive system. The proposed analysis of the reproductive system will provide important new knowledge of gene regulation driving organ development. The insights and technologies developed in this program will be widely applicable in biotechnological and pharmacogenomic research in Australia and worldwide, and assert Australia's leadership in this area of research.
Discovery Early Career Researcher Award - Grant ID: DE140101728
Funder
Australian Research Council
Funding Amount
$395,220.00
Summary
The regulation and evolution of posttranscriptional gene networks. The ability of cells to regulate gene expression is key for organism development, adaptation to new environments and evolutionary changes that shape the diversity of life on Earth. This project studies the RNA binding proteins called PUFs which are central for gene expression in diverse organisms. Using cutting-edge new generation systems biology approaches, this project will study how PUF proteins regulate genes to enable metabo ....The regulation and evolution of posttranscriptional gene networks. The ability of cells to regulate gene expression is key for organism development, adaptation to new environments and evolutionary changes that shape the diversity of life on Earth. This project studies the RNA binding proteins called PUFs which are central for gene expression in diverse organisms. Using cutting-edge new generation systems biology approaches, this project will study how PUF proteins regulate genes to enable metabolic adaptation, differentiation of cell types and the evolution of new gene expression outputs in distinct biological species. The outcomes will include new insights into the regulation and evolution of posttranscriptional gene networks. 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
The role of central carbon metabolism in cell cycle control in bacteria. Bacteria are simple organisms, yet we still do not understand how they coordinate their growth with their reproduction so faithfully, generation after generation, to produce viable newborn cells. The new discovery of a link between the food bacteria eat and the first stage of their cell division now provides the opportunity to elucidate how bacteria 'measure' their energy production to control their proliferation. This proj ....The role of central carbon metabolism in cell cycle control in bacteria. Bacteria are simple organisms, yet we still do not understand how they coordinate their growth with their reproduction so faithfully, generation after generation, to produce viable newborn cells. The new discovery of a link between the food bacteria eat and the first stage of their cell division now provides the opportunity to elucidate how bacteria 'measure' their energy production to control their proliferation. This project combines the latest technology with complementary expertise in bacterial cell division and metabolism. This should identify the mechanism that integrates these fundamental pathways in bacteria, crucial to both their survival and ability to cause infection.Read moreRead less
Identifying how bacterial cells find their middle: a new perspective. This project will reveal new information about how bacterial cells divide with high precision to ensure that each newborn cell contains the correct genetic material. The research uses frontier techniques, provides innovative training to young Australian researchers, and will identify new ways to treat infections caused by bacteria.
Rational design of genetic circuits that respond to transient signals. Engineered genetic circuits with predictable and robust behaviour promise unprecedented environmental and economic benefits. Yet much work remains to be done before living devices can routinely be built from a standarised set of biological parts - the goal of synthetic biologists. By studying how natural genetic switch circuits respond to transient signals, this project aims to uncover a set of design rules which could be use ....Rational design of genetic circuits that respond to transient signals. Engineered genetic circuits with predictable and robust behaviour promise unprecedented environmental and economic benefits. Yet much work remains to be done before living devices can routinely be built from a standarised set of biological parts - the goal of synthetic biologists. By studying how natural genetic switch circuits respond to transient signals, this project aims to uncover a set of design rules which could be used to construct and control purpose-built genetic networks and pathways. The results of this project are expected to add to the molecular tookit available to synthetic biologists.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