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
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
How does Fat cadherin control organ size in Drosophila, and cancer in humans? The primary function of Fat cadherin is to dictate the appropriate size of organs in developing animals. Deficiency in the fat gene results in vastly overgrown organs and can lead to the formation of cancer in humans. Our study will provide important insights into how the size of organs are controlled during development. Our research findings will have important implications for several aspects of human health and biol ....How does Fat cadherin control organ size in Drosophila, and cancer in humans? The primary function of Fat cadherin is to dictate the appropriate size of organs in developing animals. Deficiency in the fat gene results in vastly overgrown organs and can lead to the formation of cancer in humans. Our study will provide important insights into how the size of organs are controlled during development. Our research findings will have important implications for several aspects of human health and biology, and will increase our understanding of diseases that arise due to aberrant tissue growth, such as cancer. Our research findings will thus be of substantial national benefit, given that cancer is now the biggest cause of death in Australia, and that more than 88,000 Australians are diagnosed with cancer each year. Read moreRead less
Improved biomonitoring of urban freshwater ecosystems using DNA barcodes. This project aims to provide rapid diagnostic detection of environmental change in aquatic ecosystems at reduced cost. Next-generation sequencing (NGS) can transform monitoring of aquatic ecosystems by identifying many species in multiple biological samples. This project aims to use NGS technology to identify macroinvertebrate species as biological indicators in urban freshwater ecosystems to provide more rapid, sensitive ....Improved biomonitoring of urban freshwater ecosystems using DNA barcodes. This project aims to provide rapid diagnostic detection of environmental change in aquatic ecosystems at reduced cost. Next-generation sequencing (NGS) can transform monitoring of aquatic ecosystems by identifying many species in multiple biological samples. This project aims to use NGS technology to identify macroinvertebrate species as biological indicators in urban freshwater ecosystems to provide more rapid, sensitive and cost-effective monitoring compared to traditional methods. The project uses DNA barcodes that identify species to detect species in samples processed with NGS. The project also plans to use previously collected samples to explore species diversity and detect indicator species.Read moreRead less
Subterranean invertebrate communities of arid zone Western Australia: diversity, assessment and food-web structure. The diverse and unique subterranean fauna associated with aquifers of the Western Australia arid zone is potentially threatened by water extraction, mining and other human impacts. This project aims to apply a powerful combination of molecular genetic analyses and compound specific isotope analyses to study, for the first time, the food web structure and source of energy of these g ....Subterranean invertebrate communities of arid zone Western Australia: diversity, assessment and food-web structure. The diverse and unique subterranean fauna associated with aquifers of the Western Australia arid zone is potentially threatened by water extraction, mining and other human impacts. This project aims to apply a powerful combination of molecular genetic analyses and compound specific isotope analyses to study, for the first time, the food web structure and source of energy of these groundwater ecosystems. The project aims to also develop novel procedures for monitoring their biodiversity using environmental DNA within the groundwater. The results will provide crucial information for the management of groundwater, and conservation of their associated ecosystems, and significantly improve the rigour of long-term environmental monitoring.Read moreRead less
A study of the nongenomic action of Vitamin D: proposed role of the nuclear VDR and downstream signalling molecules. Vitamin D (1,25D) activates genes in the nucleus through the vitamin D receptor (VDR). 1,25D can also elicit rapid responses at the plasma membrane. This action is critical to the activation of nuclear genes. We hypothesise that a proportion of the nuclear VDR is located at the plasma membrane where it stimulates downstream signalling molecules eg Ras, ERK1/2 and ERK5. We plan to ....A study of the nongenomic action of Vitamin D: proposed role of the nuclear VDR and downstream signalling molecules. Vitamin D (1,25D) activates genes in the nucleus through the vitamin D receptor (VDR). 1,25D can also elicit rapid responses at the plasma membrane. This action is critical to the activation of nuclear genes. We hypothesise that a proportion of the nuclear VDR is located at the plasma membrane where it stimulates downstream signalling molecules eg Ras, ERK1/2 and ERK5. We plan to explore this hypothesis and to identify the signalling molecules. We will also investigate our novel finding that a specific Ras isoform is involved in ERK5 activation. The work will provide new information on signalling pathways.Read moreRead less
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
Evolution of sensory systems in the dark biosphere. This project utilises a unique Australian model system based on multiple, independently-evolved subterranean water beetles to explore the adaptive and regressive changes in the genome that occur when surface species colonise subterranean habitats. We aim to characterise and investigate the evolution of chemosensory and circadian rhythm genes, which play critical roles in the fitness of animals, including the ability to find food and mates in a ....Evolution of sensory systems in the dark biosphere. This project utilises a unique Australian model system based on multiple, independently-evolved subterranean water beetles to explore the adaptive and regressive changes in the genome that occur when surface species colonise subterranean habitats. We aim to characterise and investigate the evolution of chemosensory and circadian rhythm genes, which play critical roles in the fitness of animals, including the ability to find food and mates in a dark, thermally stable environment. Knowledge of chemosensory and circadian genetic systems and how they dynamically evolve is fundamental to a variety of fields, including the process of speciation and biological adaptation (for example, to permanent darkness, pollutants and insecticides).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.
Genomics for persistence of Australian freshwater fish. Biodiversity faces an unpredictable cocktail of impacts and global environmental change, against which the best insurance is genetic diversity. We will develop genomic measures of ecological-genetic functions and evolutionary potential for managing Australian freshwater fish.