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Improvement of anthracycline chemotherapy by enhancement of apoptotic responses and tumour targeted activation. Improved outcomes for anthracycline anticancer chemotherapy is of clear benefit to the nation. Tumour-localised treatment is expected to lead to improved responses, reduced side-effects and improved quality of life while rational selection of drug combinations is expected to enable treatment of tumours that were previously resistant to anthracyclines. With an aging population in Austra ....Improvement of anthracycline chemotherapy by enhancement of apoptotic responses and tumour targeted activation. Improved outcomes for anthracycline anticancer chemotherapy is of clear benefit to the nation. Tumour-localised treatment is expected to lead to improved responses, reduced side-effects and improved quality of life while rational selection of drug combinations is expected to enable treatment of tumours that were previously resistant to anthracyclines. With an aging population in Australia the incidence of cancer is predicted to rise dramatically - improved treatment outcomes and better use of chemotherapeutics will be of obvious national benefit. The development of new tumour-targeted agents is the subject of joint Intellectual Property between Australia and the USA, offering potential economic benefit. Read moreRead less
The transcriptome dynamics that refine eukaryotic gene expression. This project aims to understand the fundamental mechanisms of gene expression control, by exploring how cells respond to acute perturbation with changes to RNA expression and processing. Unlike the static information encoded within the genome, the information encoded in its intermediary RNA, is transient, plastic and responsive to environmental and developmental cues. This project will use new technologies encompassing RNA-bioche ....The transcriptome dynamics that refine eukaryotic gene expression. This project aims to understand the fundamental mechanisms of gene expression control, by exploring how cells respond to acute perturbation with changes to RNA expression and processing. Unlike the static information encoded within the genome, the information encoded in its intermediary RNA, is transient, plastic and responsive to environmental and developmental cues. This project will use new technologies encompassing RNA-biochemistry, Next Generation Sequencing, and bioinformatics to answer long-standing questions in RNA processing. The project expects to significantly enhance our understanding of the mechanisms underpinning gene-expression control, benefitting Australia by positioning it as a world leader in the field of RNA Biology.Read moreRead less
Roles of the kynurenine pathway in physiological and pathological brain function. This project will aim to study the metabolism of the essential amino acid tryptophan in the brain and its involvement in diseases including multiple sclerosis and brain tumours.
Unraveling the role of N-acetyl-aspartate in normal brain function and disease. The purpose of this project is to define the role of the predominating brain chemical N-acetyl-aspartate for normal nerve cell function and as toxic agent causing neurological illness and severe mental health problems. Findings of this research will enhance the design of novel therapies involving pharmacological and genetic treatment.
Tools for manipulating neuronal activity for behavioural studies. This project aims to develop optogenetic tools neuroscientists can use to better understand brain circuitry and the functional effects of specific neurons on behaviour. Linking the activity of individual neurons in the brain to specific behaviours is a major challenge in neuroscience. Optogenetics achieve this by using light to control the activity of neurons. This has advanced understanding of behaviour and neurocircuitry. This p ....Tools for manipulating neuronal activity for behavioural studies. This project aims to develop optogenetic tools neuroscientists can use to better understand brain circuitry and the functional effects of specific neurons on behaviour. Linking the activity of individual neurons in the brain to specific behaviours is a major challenge in neuroscience. Optogenetics achieve this by using light to control the activity of neurons. This has advanced understanding of behaviour and neurocircuitry. This project is expected to increase understanding of brain function at the cellular and system levels, and advance Australia’s multidisciplinary research capacity in neuroscience, cognitive sciences and nanobiotechnology to ultimately treat neurological disorders.Read moreRead less
Investigating the molecular mechanisms underlying non-visual photoreception and their implications in the treatment of human neurological disease. The ability of organisms to detect light is fundamental for survival and has been a major driver in evolution. The project will investigate the genetic origins of the various visual and non-visual systems and will explore its implications for the bioengineering of therapeutics for the treatment of neurological disease in humans.
Synthetic genes as reference standards for biology and biomanufacture. Reference standards are needed to improve the measurement of biology and the reliability of biomanufacturing processes. This project aims to engineer synthetic genes capable of acting as reference standards for DNA, RNA and protein. The synthetic genes can be transcribed into mRNA standards, and translated into protein standards, and be further integrated into living cells to measure internal cellular processes.
The outcomes ....Synthetic genes as reference standards for biology and biomanufacture. Reference standards are needed to improve the measurement of biology and the reliability of biomanufacturing processes. This project aims to engineer synthetic genes capable of acting as reference standards for DNA, RNA and protein. The synthetic genes can be transcribed into mRNA standards, and translated into protein standards, and be further integrated into living cells to measure internal cellular processes.
The outcomes include a unified understanding of gene expression and more accurate next-generation sequencing and mass-spectrophotometry technologies. The synthetic genes also allow standardisation and optimisation of biomanufacturing processes that will produce mRNA and biologics products at a higher purity and lower cost.Read moreRead less
Defining the cellular impacts of protein aggregation in neurodegenerative disease with an aggreomics platform. The brain disease Huntington’s is caused by abnormally shaped proteins that assemble into toxic clusters. This project will design new bioprobes to track how these clusters form and cause damage to cells. This strategy will also provide new opportunities for discovering novel therapeutic targets.
Single-molecule optofluidics: streamlining high-throughput engineering and analysis of proteins and protein assemblies. This project aims at creating novel technologies for high-throughput engineering and analysis of proteins with single-molecule sensitivity. The platform will considerably accelerate the generation of protein-based diagnostics, new vaccines and therapeutics; it will foster collaborations with industry putting Australia at the forefront of protein research.
DNA end resection: from basic mechanisms to genome editing. The project aims to understand processes underlying genome editing, a bioengineering process that introduces specific mutations into genomic DNA. Homologous recombination and nonhomologous end-joining pathways play a crucial role in repairing broken DNA strands, which are a toxic form of DNA damage. The proteins that function in the repair process have been recently identified, but it remains unclear how they function on a mechanistic l ....DNA end resection: from basic mechanisms to genome editing. The project aims to understand processes underlying genome editing, a bioengineering process that introduces specific mutations into genomic DNA. Homologous recombination and nonhomologous end-joining pathways play a crucial role in repairing broken DNA strands, which are a toxic form of DNA damage. The proteins that function in the repair process have been recently identified, but it remains unclear how they function on a mechanistic level and how either of the two main pathways is selected. The project aims to define how the activity of a key control protein, Sae2 (Sporulation in the Absence of Spo Eleven), is regulated by posttranslational modifications, and how this activates homologous recombination. The project plans to first use Saccharomyces cerevisiae yeast as a model and then to extend research into the human system in an attempt to improve the efficiency of genome editing. Read moreRead less