Visualising molecular level detail in single cells and intact tissues. The goal of this project is to deliver a new toolkit for imaging cells at an unprecedented resolution and level of chemical detail. We will expand the capabilities of two existing, but complementary, methods: optical fluorescence microscopy with responsive probes and X-ray fluorescence imaging. Expected outcomes include improved techniques and benchmarks for visualising bacterial and mammalian cells; development of new molecu ....Visualising molecular level detail in single cells and intact tissues. The goal of this project is to deliver a new toolkit for imaging cells at an unprecedented resolution and level of chemical detail. We will expand the capabilities of two existing, but complementary, methods: optical fluorescence microscopy with responsive probes and X-ray fluorescence imaging. Expected outcomes include improved techniques and benchmarks for visualising bacterial and mammalian cells; development of new molecules for elucidating cellular chemistry; better utilisation of valuable synchrotron resources; and greater understanding of the strengths and limitations of current microscopy workflows. Results should benefit the biotechnology sector, and may lead to improved medical, diagnostic, and bioremediation capacity.Read moreRead less
Revealing molecular detail of DNA triplexes to underpin antigene technology. Variations from the classic DNA double helix structure are proposed to play key roles in a range of cellular processes, particularly gene regulation. However, the biological function and therapeutic potential of these unusual DNA structures are poorly explored, since the fundamental molecular details which govern their formation and interactions with cellular machinery are not well described. This project aims to develo ....Revealing molecular detail of DNA triplexes to underpin antigene technology. Variations from the classic DNA double helix structure are proposed to play key roles in a range of cellular processes, particularly gene regulation. However, the biological function and therapeutic potential of these unusual DNA structures are poorly explored, since the fundamental molecular details which govern their formation and interactions with cellular machinery are not well described. This project aims to develop innovative methods to investigate, and importantly modulate, DNA and RNA triple helix assembly, specificity and molecular interactions. Resulting insights will underpin novel approaches to gene regulation, principally in the context of designing new antibacterial agents to address the antibacterial resistance problem.Read moreRead less
Can parasites cause host population divergence? . Parasites have been proposed to be drivers of population divergence, and ultimately speciation, yet the dynamics of this process are not well understood. This project will utilise new genomic techniques, novel hybrid zone analyses, and data on mate choice, to investigate the hypothesis that parasites drive population divergence through an interaction with immune response genes in the sleepy lizard Tiliqua rugosa. This species provides an unpreced ....Can parasites cause host population divergence? . Parasites have been proposed to be drivers of population divergence, and ultimately speciation, yet the dynamics of this process are not well understood. This project will utilise new genomic techniques, novel hybrid zone analyses, and data on mate choice, to investigate the hypothesis that parasites drive population divergence through an interaction with immune response genes in the sleepy lizard Tiliqua rugosa. This species provides an unprecedented system, backed by 37 years of long term host-parasite and behavioural data, and recent genetic analyses. This project intends to produce significant data to allow an examination of the early stages of host-parasite evolution in action, providing novel insights into the speciation process. Read moreRead less
Glauconite: Archive Recording Timing and Triggers of Cambrian Radiation . This project aims to constrain the timing and speed of the Cambrian radiation of complex animals, and to test potential environmental triggers of this milestone bioevent. New laser mass spectrometry and mineral mapping technology will be integrated to precisely date glauconite – a silicate mineral commonly formed in Cambrian shallow marine animal habitats. This innovative and cost-effective approach will produce the first ....Glauconite: Archive Recording Timing and Triggers of Cambrian Radiation . This project aims to constrain the timing and speed of the Cambrian radiation of complex animals, and to test potential environmental triggers of this milestone bioevent. New laser mass spectrometry and mineral mapping technology will be integrated to precisely date glauconite – a silicate mineral commonly formed in Cambrian shallow marine animal habitats. This innovative and cost-effective approach will produce the first high-resolution timeline of early animal evolution, where the glauconite-based marine isotope record identifies the most likely environmental trigger for the Cambrian Radiation. Outcomes of this study include improved understanding of the drivers of animal evolution, and a new dating tool for basic and applied research.Read moreRead less
Safer gene editing tools for Australian livestock and biotech industries. Editing the genome of an organism in an efficient and safe fashion is critical for the livestock and biotechnology industries. While CRISPR-Cas9 has become the method of choice for genome editing, it is known to introduce unwanted "on-target" and "off-target" mutations, limiting its utility. To address this the CI team created a novel genome editing platform technology termed Crackling-CAST that is almost 100% accurate, w ....Safer gene editing tools for Australian livestock and biotech industries. Editing the genome of an organism in an efficient and safe fashion is critical for the livestock and biotechnology industries. While CRISPR-Cas9 has become the method of choice for genome editing, it is known to introduce unwanted "on-target" and "off-target" mutations, limiting its utility. To address this the CI team created a novel genome editing platform technology termed Crackling-CAST that is almost 100% accurate, while retaining the efficiency of the classical Cas9 system. This project will exemplify the capabilities of the novel gene targeting platform in cell types used by the biotechnology and livestock sectors, ensuring its global uptake by these industries and delivering significant economic benefits for Australia. Read moreRead less
Bacterial polycyclic aromatic hydrocarbon transport and degradation. This project aims to investigate the molecular processes underpinning the degradation of polycyclic aromatic hydrocarbons (PAHs) by bacteria. PAHs are persistent environmental contaminants linked to several human diseases, including cancer. Bacteria capable of degrading PAHs could be used to naturally and effectively reduce environmental PAH loads to below safe levels. The project will apply techniques in functional genomics an ....Bacterial polycyclic aromatic hydrocarbon transport and degradation. This project aims to investigate the molecular processes underpinning the degradation of polycyclic aromatic hydrocarbons (PAHs) by bacteria. PAHs are persistent environmental contaminants linked to several human diseases, including cancer. Bacteria capable of degrading PAHs could be used to naturally and effectively reduce environmental PAH loads to below safe levels. The project will apply techniques in functional genomics and biochemistry to help define the ways that PAHs are taken up from the environment by bacteria, their fate within bacterial cells, and the ways that bacteria overcome the inherent toxicity of PAHs. The knowledge generated is expected to enhance our capacity to rationally deploy bacteria for PAH degradation.Read moreRead less
Mycobacterial Cholesterol Degradation: A Unique Metabolic Weakness? This project aims to understand the use of the steroid cholesterol as a source of essential metabolic building blocks by bacteria. Cholesterol utilisation is a key feature of many bacterial pathogens which have evolved to survive in niche environments. By understanding the initial step in cholesterol degradation and the bioinorganic and bioorganic chemistry of the metalloenzymes that catalyse it, this work aims to develop strate ....Mycobacterial Cholesterol Degradation: A Unique Metabolic Weakness? This project aims to understand the use of the steroid cholesterol as a source of essential metabolic building blocks by bacteria. Cholesterol utilisation is a key feature of many bacterial pathogens which have evolved to survive in niche environments. By understanding the initial step in cholesterol degradation and the bioinorganic and bioorganic chemistry of the metalloenzymes that catalyse it, this work aims to develop strategies to block this activity. This will turn a key strength of these bacteria into a potent weakness and will generate the proof of principle and knowledge required for the future development of effective strategies to combat pathogenic bacteria.Read moreRead less
Investigating the evolution of innate and adaptive cellular immunity. This proposal aims to assess the impact of geographical and genetic isolation of the Australian Indigenous population on adaptive and innate immune systems. The project will use novel DNA sequencing approaches to generate the high resolution sequences of two genetic loci that regulate innate and adaptive immune responses, the major histocompatibility complex locus and the killer cell immunoglobulin-like receptor locus. In an i ....Investigating the evolution of innate and adaptive cellular immunity. This proposal aims to assess the impact of geographical and genetic isolation of the Australian Indigenous population on adaptive and innate immune systems. The project will use novel DNA sequencing approaches to generate the high resolution sequences of two genetic loci that regulate innate and adaptive immune responses, the major histocompatibility complex locus and the killer cell immunoglobulin-like receptor locus. In an initial screen, distinct variants and combinations of these genes were identified. This project aims to interrogate how variation in these critical genes impacts on the function of cytotoxic lymphocytes, providing insights into the evolutionary drivers of immune recognition mechanisms.Read moreRead less
Physiology of oxygen transport in the mammalian kidney. This project aims to improve understanding of oxygen regulation in renal tissue and knowledge of the physiology of the kidney. The mammalian kidney receives more oxygen than it uses or needs, and yet renal tissue is commonly found to be hypoxic. This project proposes that oxygen transport to the renal tissue is limited by blood vessel surface area. The project expects to generate anatomical data currently missing from the renal physiology c ....Physiology of oxygen transport in the mammalian kidney. This project aims to improve understanding of oxygen regulation in renal tissue and knowledge of the physiology of the kidney. The mammalian kidney receives more oxygen than it uses or needs, and yet renal tissue is commonly found to be hypoxic. This project proposes that oxygen transport to the renal tissue is limited by blood vessel surface area. The project expects to generate anatomical data currently missing from the renal physiology community, and potentially change the accepted story of oxygen homeostasis in the kidney. This will provide significant benefits, such as the provision of the foundational physiological science behind a determinant of kidney health and its flow-on impact to quality of life.Read moreRead less
How does timing affect mammalian brain development and evolution? This project aims to generate fundamental knowledge on the origin of diversity in mammalian brain circuits by studying development of marsupials and rodents. The expected outcome is to elucidate how differences in the timing, rate and sequence of development of gene expression, cell differentiation and circuit formation can relate to the origin of key evolutionary innovations in the mammalian brain. The significance of understandi ....How does timing affect mammalian brain development and evolution? This project aims to generate fundamental knowledge on the origin of diversity in mammalian brain circuits by studying development of marsupials and rodents. The expected outcome is to elucidate how differences in the timing, rate and sequence of development of gene expression, cell differentiation and circuit formation can relate to the origin of key evolutionary innovations in the mammalian brain. The significance of understanding the dynamics of developmental systems that shape complex brain traits includes establishing new developmental paradigms in evolutionary theory, generating new tools to investigate and manipulate brain gene expression in vivo, and the potential discovery of the causes of neurodevelopmental dysfunction.Read moreRead less