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Molecular Diagnosis And Therapy Of Autoimmune Disease Using Translational And Reverse Translational Approaches
Funder
National Health and Medical Research Council
Funding Amount
$2,331,372.00
Summary
We plan to translate our recent discoveries on human gene variants and molecules produced by immune cells (follicular T cells) into effective therapies for autoimmune diseases. This will involve understanding the mechanisms by which the genes and molecules regulate immune tolerance, stratifying patients with autoimmune disease using newly identified biomarkers, trialling existing biologicals according to affected molecular pathway, and taking novel targets through to commercialisation.
High-throughput single-molecule directed evolution. DNA polymerases are essential enzymes in many biotechnological tools, including DNA sequencing and PCR tests. However, existing DNA polymerases have limitations, resulting in inaccuracies and inefficiencies. Existing methods to improve polymerases lack sensitivity to screen for subtle, yet pivotal traits. This project aims to overcome this limitation by developing a new single-molecule directed-evolution system to evolve better polymerases. Wit ....High-throughput single-molecule directed evolution. DNA polymerases are essential enzymes in many biotechnological tools, including DNA sequencing and PCR tests. However, existing DNA polymerases have limitations, resulting in inaccuracies and inefficiencies. Existing methods to improve polymerases lack sensitivity to screen for subtle, yet pivotal traits. This project aims to overcome this limitation by developing a new single-molecule directed-evolution system to evolve better polymerases. With this new technology we aim to identify DNA polymerases with improved performance that benefit biotechnological applications. Additionally, these single-molecule directed-evolution methods will benefit the wider scientific community and lay the foundation for further advances in directed evolution.Read moreRead less
Targeting the host lipid environment to disrupt malaria transmission. This project aims to characterise host molecules (in particular lipids) that are crucial for the transition of malaria parasites from one host to another. Malaria parasites encounter different environments upon their transition from human to the mosquito host. This project expects to generate new knowledge on physiological changes that are triggered by particular differences in micronutrient abundance that allow the parasites ....Targeting the host lipid environment to disrupt malaria transmission. This project aims to characterise host molecules (in particular lipids) that are crucial for the transition of malaria parasites from one host to another. Malaria parasites encounter different environments upon their transition from human to the mosquito host. This project expects to generate new knowledge on physiological changes that are triggered by particular differences in micronutrient abundance that allow the parasites to survive in the new host. Anticipated outcomes include the identification of new intervention strategies and improved transmission model systems for vector-borne diseases. This gained knowledge could provide benefits to future biomedical applications by informing diagnostics or treatment of lipid associated diseases.Read moreRead less
About time; a new biology for the mineralocorticoid receptor . Temporal control of cell function aligns biological pathways with environmental cues and is critical for optimal heath in mammals. This project will shed light on how a hormone receptor, the MR, modulates time keeping of biological clock time in cells. We will bring together cutting edge genetic modals and bioinformatic approaches with a unique set of research models to define the interaction between the MR and the circadian clock a ....About time; a new biology for the mineralocorticoid receptor . Temporal control of cell function aligns biological pathways with environmental cues and is critical for optimal heath in mammals. This project will shed light on how a hormone receptor, the MR, modulates time keeping of biological clock time in cells. We will bring together cutting edge genetic modals and bioinformatic approaches with a unique set of research models to define the interaction between the MR and the circadian clock and its role in the normal biology of the heart. New data will significantly enhance our understanding of the biology of MR and cortisol for the circadian time keeping function in peripheral tissues, and gain a clearer understand how our heart cells adapt to environmental circadian disruptors such as shift work. Read moreRead less
What drives the Anterior Expansion of the Central Nervous System? A striking and highly conserved feature of the central nervous system is that the brain is larger than the spinal cord. Despite the manifest implications this has for nervous system function, the underlying drivers are largely unknown. This project aims to investigate the mechanisms controlling anterior expansion of the central nervous system, and will generate new knowledge in the areas of nervous system development and evolution ....What drives the Anterior Expansion of the Central Nervous System? A striking and highly conserved feature of the central nervous system is that the brain is larger than the spinal cord. Despite the manifest implications this has for nervous system function, the underlying drivers are largely unknown. This project aims to investigate the mechanisms controlling anterior expansion of the central nervous system, and will generate new knowledge in the areas of nervous system development and evolution. This project aims to impact on our understanding of nervous system function, develop bioinformatics tools with broad utility within the biosciences field, strengthen Australia’s international standing in the developmental neuroscience, and enhance the capacity for interdisciplinary international collaborations.Read moreRead less
Structures to Solve Conflicts of DNA Replication and RNA Transcription. This project aims to understand how new DNA is made so quickly and without mistakes in cells that are about to divide, in spite of competition from other processes happening at the same time on the DNA that should stop or interfere with it, such as the synthesis of RNA. The project expects to use the latest available methods to uncover what the microscopic natural machines that make DNA and RNA look like, and how they compet ....Structures to Solve Conflicts of DNA Replication and RNA Transcription. This project aims to understand how new DNA is made so quickly and without mistakes in cells that are about to divide, in spite of competition from other processes happening at the same time on the DNA that should stop or interfere with it, such as the synthesis of RNA. The project expects to use the latest available methods to uncover what the microscopic natural machines that make DNA and RNA look like, and how they compete with each other for access to DNA. Potential outcomes include the identification of processes that can be compromised by small molecules that may be developed into new antibiotics. This would be of great benefit - new antibiotics are urgently needed as one approach to countering the threat of antimicrobial resistance.Read moreRead less
Co-designing Innovations in Digital Storytelling with Older Adults. This project aims to investigate how emerging technologies can be leveraged to provide innovative ways for older adults to create and share their life stories to foster social wellbeing. Later life can be a time of considerable change, leaving people feeling disconnected from the people, places, and life events that are important to them. Autobiographical storytelling can help create links with one's past, but little is known ab ....Co-designing Innovations in Digital Storytelling with Older Adults. This project aims to investigate how emerging technologies can be leveraged to provide innovative ways for older adults to create and share their life stories to foster social wellbeing. Later life can be a time of considerable change, leaving people feeling disconnected from the people, places, and life events that are important to them. Autobiographical storytelling can help create links with one's past, but little is known about how technologies such as digital games and virtual reality can be used to enable older adults to share stories about their lives in a way that supports ongoing social interactions. This project is expected to co-design new forms of digital storytelling to improve social wellbeing of older adults. Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE240100780
Funder
Australian Research Council
Funding Amount
$455,237.00
Summary
Functional and structural dissection of the human replisome. This project aims to develop technology to visualise the structure and enzymatic activities of the human replisome, the multiprotein assembly that copies DNA before cell division. A combination of novel single-molecule and state-of-the-art cryo-electron microscopy will be used to define how the human replisome coordinates DNA synthesis during times of replication stress. Key outcomes of this project include development of novel molecul ....Functional and structural dissection of the human replisome. This project aims to develop technology to visualise the structure and enzymatic activities of the human replisome, the multiprotein assembly that copies DNA before cell division. A combination of novel single-molecule and state-of-the-art cryo-electron microscopy will be used to define how the human replisome coordinates DNA synthesis during times of replication stress. Key outcomes of this project include development of novel molecular visualisation technologies, leading to the first molecular description of dynamic processes used by the human replisome. Benefits include improved understanding of a fundamental biological process that often malfunctions in cancers, development of novel methodology, and interdisciplinary training.Read moreRead less
A novel platform for the biosynthesis of commercially valuable saxitoxins. Saxitoxins are potent microbial toxins, which pose a significant threat to food and water quality. Highly pure saxitoxins are required for environmental monitoring and studies of cell physiology. Certain analogues have also shown promise as long-lasting and non-addictive pain blockers. However, the procurement of these compounds from natural sources is convoluted and unsustainable. This project aims to use the latest synt ....A novel platform for the biosynthesis of commercially valuable saxitoxins. Saxitoxins are potent microbial toxins, which pose a significant threat to food and water quality. Highly pure saxitoxins are required for environmental monitoring and studies of cell physiology. Certain analogues have also shown promise as long-lasting and non-addictive pain blockers. However, the procurement of these compounds from natural sources is convoluted and unsustainable. This project aims to use the latest synthetic biology techniques to characterise, modify and express saxitoxin biosynthesis pathways, thereby providing a sustainable source of toxin analogues of value to industry and research. This novel 'green technology' will benefit the environment, human health and the Australian economy.Read moreRead less
Mid-Career Industry Fellowships - Grant ID: IM230100154
Funder
Australian Research Council
Funding Amount
$1,049,904.00
Summary
Fungi Power: Designer Fungal Cell Factories for Advanced Biomanufacturing. This project aims to build an advanced biomanufacturing platform based on filamentous fungi in collaboration with industry. Using synthetic biology, the project expects to engineer superior fungal host strains customisable to the needs of the industry and to address their technological gaps. The expected outcomes include the development of cost-efficient and sustainable fungal-based bioprocesses for the companies to produ ....Fungi Power: Designer Fungal Cell Factories for Advanced Biomanufacturing. This project aims to build an advanced biomanufacturing platform based on filamentous fungi in collaboration with industry. Using synthetic biology, the project expects to engineer superior fungal host strains customisable to the needs of the industry and to address their technological gaps. The expected outcomes include the development of cost-efficient and sustainable fungal-based bioprocesses for the companies to produce products, such as fine chemicals, pharmaceutical actives and food ingredients. The project would provide significant benefits by enabling existing and emerging companies' commercial successes and competitiveness in global markets, creating new jobs and resulting in the growth of the bio-economy in Australia.Read moreRead less