Structural domains of beta-tubulin and their role in microtubule dynamics and transport. This study aims to obtain a fundamental understanding of how the structural domains of the cytoskeletal protein beta-tubulin are involved in microtubule structures during cell division and vesicular transport. Using gene-editing technology and coupling this with cell biological approaches and high-resolution cell imaging will enable detailed analysis of the role of beta-tubulin domains in these important cel ....Structural domains of beta-tubulin and their role in microtubule dynamics and transport. This study aims to obtain a fundamental understanding of how the structural domains of the cytoskeletal protein beta-tubulin are involved in microtubule structures during cell division and vesicular transport. Using gene-editing technology and coupling this with cell biological approaches and high-resolution cell imaging will enable detailed analysis of the role of beta-tubulin domains in these important cellular processes. The outcomes will include fundamental new knowledge in cell biology and lead to the development of unique biological models that can be used to understand disease.Read moreRead less
Understanding Mitotic Telomere Deprotection. This project aims to study telomeres, the DNA and protein structures that protect chromosome ends. During cell division, cells under stress intentionally uncap their telomeres. This project expects to generate new knowledge that challenges the conventional notion of telomeres as static elements, showing instead that telomeres can be dynamic signalling hubs. Expected outcomes of this project include an understanding of the genetic, proteomic, and signa ....Understanding Mitotic Telomere Deprotection. This project aims to study telomeres, the DNA and protein structures that protect chromosome ends. During cell division, cells under stress intentionally uncap their telomeres. This project expects to generate new knowledge that challenges the conventional notion of telomeres as static elements, showing instead that telomeres can be dynamic signalling hubs. Expected outcomes of this project include an understanding of the genetic, proteomic, and signalling pathways involved in this novel phenomenon. This should provide significant benefits to our fundamental understanding of biological processes that protect human genomes and provide a valuable dataset for research on telomere biology, DNA repair, and genome stability.Read moreRead less
Dissecting cell cycle regulation using programmable gene editing technology. This program aims to harness the unprecedented power of CRISPR-Cas13 gene-editing technology to develop high-throughput tools to explore the role of RNA regulation in cell cycle control. This project expects to generate new knowledge about cell division and RNA biology by utilizing this new technology and applying interdisciplinary approaches. Expected outcomes of this proposal include new research tools capable of broa ....Dissecting cell cycle regulation using programmable gene editing technology. This program aims to harness the unprecedented power of CRISPR-Cas13 gene-editing technology to develop high-throughput tools to explore the role of RNA regulation in cell cycle control. This project expects to generate new knowledge about cell division and RNA biology by utilizing this new technology and applying interdisciplinary approaches. Expected outcomes of this proposal include new research tools capable of broadly addressing biological questions across multiple disciplines (e.g. from health to food production). This project intends to provide significant benefits, such as enhanced biological knowledge, multidisciplinary training opportunities and will build Australia’s capability in this rapidly expanding field.Read moreRead less
Understanding telomere privilege in pluripotent stem cells. We recently identified that fundamental mechanisms which protect chromosome ends (i.e. “telomeres”) are not conserved between somatic and embryo-derived stem cells. This discovery is without precedent and challenges the dogmatic expectation that cellular functions promoting genome stability are conserved in stem cells. We term the unexpected protective capacity of pluripotent chromosome ends “telomere privilege”. Here we will uncover th ....Understanding telomere privilege in pluripotent stem cells. We recently identified that fundamental mechanisms which protect chromosome ends (i.e. “telomeres”) are not conserved between somatic and embryo-derived stem cells. This discovery is without precedent and challenges the dogmatic expectation that cellular functions promoting genome stability are conserved in stem cells. We term the unexpected protective capacity of pluripotent chromosome ends “telomere privilege”. Here we will uncover the molecular, genomic, and proteomic regulators or telomere privilege; determine the breath of telomere privilege in stem cell lineages; elucidate the functional significance of telomere privilege; and exploit telomere privilege to study fundamental biology related to telomeres and the DNA damage response.Read moreRead less
The control of chromosome division during female meiosis. Mammalian eggs are stored life-long and finally mature in the hours before ovulation. This project examines how the chromosomes in the egg are separated properly so as to produce a mature egg capable of being fertilized by a sperm. Often in eggs chromosome division is imprecisely executed, and this project will help us understand why this occurs.
Exploring the gene regulation networks governing mitochondrial biogenesis in Arabidopsis. Mitochondria, subcellular organelles that perform many functions indispensable to plant growth and productivity, are dynamic compartments whose protein complement changes dramatically during plant development and under stress. Yet, the cellular processes that regulate the production of these organelles are virtually unknown. By combining conventional approaches with an extremely powerful holistic method for ....Exploring the gene regulation networks governing mitochondrial biogenesis in Arabidopsis. Mitochondria, subcellular organelles that perform many functions indispensable to plant growth and productivity, are dynamic compartments whose protein complement changes dramatically during plant development and under stress. Yet, the cellular processes that regulate the production of these organelles are virtually unknown. By combining conventional approaches with an extremely powerful holistic method for simultaneously examining the expression patterns of every gene in the model plant Arabidopsis, this project will identify proteins that regulate mitochondrial biosynthesis and uncover the gene networks that these proteins control. The project outcomes will provide new opportunities for the rational manipulation of plant growth and productivity.Read moreRead less
The MYB gene as a model for global transcriptional regulation: stopping, starting and looping. This project will study how transcriptional elongation controls the MYB gene, a key regulator of normal and cancerous growth and regulation. There are three major benefits that are likely to flow from the proposed research It will strengthen research in new and important areas of transcriptional regulation, by building research capacity in Australia in the area of gene expression, particularly with res ....The MYB gene as a model for global transcriptional regulation: stopping, starting and looping. This project will study how transcriptional elongation controls the MYB gene, a key regulator of normal and cancerous growth and regulation. There are three major benefits that are likely to flow from the proposed research It will strengthen research in new and important areas of transcriptional regulation, by building research capacity in Australia in the area of gene expression, particularly with respect to transcriptional elongation and long-range regulation. It will highlight a new approach to the therapeutic targeting of MYB in cancer: data generated from this research may enable us to target MYB expression in a range of cancers including breast cancer by inhibiting transcriptional elongation. And it will provide training in advanced molecular biology to postdoctoral scientists and students.Read moreRead less
Exploration of a mechanistic link between eukaryotic transcription and translation. Gene transcription is functionally coupled to other aspects of eukaryotic mRNA metabolism, emphasizing a need for integrated approaches to analyse the gene expression pathway. We have shown in previous work that yeast cells, when responding to external stimuli, show a tight correlation between changes in the transcriptome composition and homodirectional alterations in the translation state of mRNAs. This phenomen ....Exploration of a mechanistic link between eukaryotic transcription and translation. Gene transcription is functionally coupled to other aspects of eukaryotic mRNA metabolism, emphasizing a need for integrated approaches to analyse the gene expression pathway. We have shown in previous work that yeast cells, when responding to external stimuli, show a tight correlation between changes in the transcriptome composition and homodirectional alterations in the translation state of mRNAs. This phenomenon of ?potentiation? may serve to amplify signal-induced changes in the transcriptome at the translational level. This project will begin to unravel the molecular mechanisms underlying potentiation using experiments designed to distinguish between transcription- and translation-driven mechanisms.Read moreRead less
A role for Cited2, Transforming Growth Factor-beta and matrix metaloproteinases in trophoblast invasion and placenta formation. The placenta is essential for the growth and development of the fetus, and if it fails to form correctly during pregnancy, it can have dramatic effects that can result death in utero, or adult onset diseases. Our research aims to understand how one protein functions in placenta formation. We will also investigate how this protein works at the molecular level in a proces ....A role for Cited2, Transforming Growth Factor-beta and matrix metaloproteinases in trophoblast invasion and placenta formation. The placenta is essential for the growth and development of the fetus, and if it fails to form correctly during pregnancy, it can have dramatic effects that can result death in utero, or adult onset diseases. Our research aims to understand how one protein functions in placenta formation. We will also investigate how this protein works at the molecular level in a process that enables single cells to respond to molecules sent from a distance by other cells (TGF-beta signalling). This process is also very important for a host of other biological processes relevant to human health, including cancer.Read moreRead less