Mapping networks governing cell state plasticity: how, where and when? Single cell organisms are the basic unit of life, yet, if they had not developed the ability to change cell states we would not exist today. Changing cell states lies at the core of almost every developmental and disease process in multicellular organisms. Building upon our fundamental discovery that stem cells and non-stem cells readily interconvert, we will now incorporate innovative cell systems and the development of our ....Mapping networks governing cell state plasticity: how, where and when? Single cell organisms are the basic unit of life, yet, if they had not developed the ability to change cell states we would not exist today. Changing cell states lies at the core of almost every developmental and disease process in multicellular organisms. Building upon our fundamental discovery that stem cells and non-stem cells readily interconvert, we will now incorporate innovative cell systems and the development of our new multi-layered systems biology strategy to elucidate the first comprehensive understanding of the cell biology that underlies cell state changes. These studies are a major step toward understanding the fundamentals of life. Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE210100103
Funder
Australian Research Council
Funding Amount
$459,674.00
Summary
Fortifying animal and plant germ cells against proteotoxic stress. Cellular stress is responsible for widespread inefficiencies in plant and animal reproduction. Using high resolution proteomics and cryo-electron microscopy, this project aims to investigate how plant and animal germ cells respond to environmental stresses that are known to disrupt fertility, and assess two novel strategies to decrease the sensitivity of cells to stress. This project is expected to generate new global knowledge i ....Fortifying animal and plant germ cells against proteotoxic stress. Cellular stress is responsible for widespread inefficiencies in plant and animal reproduction. Using high resolution proteomics and cryo-electron microscopy, this project aims to investigate how plant and animal germ cells respond to environmental stresses that are known to disrupt fertility, and assess two novel strategies to decrease the sensitivity of cells to stress. This project is expected to generate new global knowledge in the area of fertility regulation with the potential to improve the tolerance of crop species to heat stress, prevent economic losses and help to secure future food production. Further, this project has the intended benefit of improving the fertility of animal species that suffer from stress-induced infertility.
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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
Control of developmental switches by importin 5. Aims: This project will study a key molecular switch called IPO5, a protein that is required for cells and organs to form and function normally, and it will reveal how it works.
Significance: These experiments will provide the first complete description of how this molecular switch controls the behaviour of a cell across its lifespan. IPO5 is highly conserved, so these studies will be relevant to a wide range of animals.
Expected Outcomes: This k ....Control of developmental switches by importin 5. Aims: This project will study a key molecular switch called IPO5, a protein that is required for cells and organs to form and function normally, and it will reveal how it works.
Significance: These experiments will provide the first complete description of how this molecular switch controls the behaviour of a cell across its lifespan. IPO5 is highly conserved, so these studies will be relevant to a wide range of animals.
Expected Outcomes: This knowledge will reveal how IPO5 controls formation of sperm by revealing what other proteins it binds to and how this affects cell signaling and responses to the environment.
Benefits: This will provide information about potential interventions to control fertility or to repair abnormal cells.
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Understanding platinum dissolution in biomedical stimulating electrodes. Platinum is the main material used in electrodes for neurostimulators like the cochlear implant. Platinum electrodes can experience dissolution during implantation, which can impact on their function. The mechanisms governing this dissolution process are complex and still not fully understood. This research aims to understand the chemical, electrical and biological factors that impact on platinum dissolution in electrodes. ....Understanding platinum dissolution in biomedical stimulating electrodes. Platinum is the main material used in electrodes for neurostimulators like the cochlear implant. Platinum electrodes can experience dissolution during implantation, which can impact on their function. The mechanisms governing this dissolution process are complex and still not fully understood. This research aims to understand the chemical, electrical and biological factors that impact on platinum dissolution in electrodes. It will also develop new 3D models to simulate conditions in the human body for more rapid testing of electrodes. The new knowledge generated will improve the accuracy of predictions of platinum dissolution, develop new approaches for minimising dissolution, and contribute to reducing need for animal experimentation.Read moreRead less
Micro-dissection of clathrins role in mitosis via chemical biology probes. This project aims to contribute to understanding the molecular mechanisms of the role of a key protein, clathrin, in cell division. In doing so it expects to reveal new approaches to stop uncontrolled cell division and proliferation, the hallmarks of cancer. The outcomes could in the long term inform breakthroughs in cancer treatment, significant enhancements in life quality and a reduction in cancer death rates.
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE210100001
Funder
Australian Research Council
Funding Amount
$875,000.00
Summary
A 3-photon imaging system for deep live imaging. This project aims to establish Australia’s first 3-photon microscope system with adaptive optics for deep intravital imaging. This advanced imaging system will enable researchers to investigate the biology of cells and tissue structures in a wide range of organs and engineered tissues, to a degree not possible with existing technology. This project will capitalise on advanced laser, microscope and adaptive optics technologies with the expected out ....A 3-photon imaging system for deep live imaging. This project aims to establish Australia’s first 3-photon microscope system with adaptive optics for deep intravital imaging. This advanced imaging system will enable researchers to investigate the biology of cells and tissue structures in a wide range of organs and engineered tissues, to a degree not possible with existing technology. This project will capitalise on advanced laser, microscope and adaptive optics technologies with the expected outcomes to include the generation of new knowledge of major biological systems, including the immune system and the nervous system. This will provide significant benefits to fundamental interdisciplinary research into immunology, infectious disease, neuroscience, mechanobiology and engineering.Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE220100006
Funder
Australian Research Council
Funding Amount
$383,872.00
Summary
Determining the regulation of ovary development with single cell sequencing. This project will greatly advance our understanding of ovary development and mammalian reproduction. I will investigate the process of ovarian primordial follicle activation including its genetic regulation, the importance of supportive granulosa cells and the biological significance of regulatory factors. This will be achieved through the comprehensive investigation of a single cell transcriptomic dataset of ovarian de ....Determining the regulation of ovary development with single cell sequencing. This project will greatly advance our understanding of ovary development and mammalian reproduction. I will investigate the process of ovarian primordial follicle activation including its genetic regulation, the importance of supportive granulosa cells and the biological significance of regulatory factors. This will be achieved through the comprehensive investigation of a single cell transcriptomic dataset of ovarian development (Aim 1) in conjunction with functional studies (Aim 2). The outcomes of which will hold significant benefit to animal reproduction through new strategies to improve livestock productivity and control invasive pest species. These outcomes are of economic and environmental and benefit nationally.Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE220100032
Funder
Australian Research Council
Funding Amount
$379,264.00
Summary
Banking on spermatogonial stem cells to safeguard Australian native fauna. Spermatogonial stem cells in the testis are an untapped resource for species conservation. This project aims to characterise metabolic pathways that control spermatogonial stem cell function, and define the conserved nature of these pathways between model species (mouse) and vulnerable Australian native fauna. Expected outcomes of this project include an enhanced capacity to culture koala spermatogonia in vitro, which wil ....Banking on spermatogonial stem cells to safeguard Australian native fauna. Spermatogonial stem cells in the testis are an untapped resource for species conservation. This project aims to characterise metabolic pathways that control spermatogonial stem cell function, and define the conserved nature of these pathways between model species (mouse) and vulnerable Australian native fauna. Expected outcomes of this project include an enhanced capacity to culture koala spermatogonia in vitro, which will be a first step towards using spermatogonial biobanking as a tool to maintain genetic diversity in this species. Outcomes from this study should provide significant benefits in safeguarding our unique Australian native species, which is of particular importance following the catastrophic 2019/20 bushfire season.Read moreRead less
New guardians of the mucosa: Molecular characterisation of M cell biology. We aim to completely define the cellular and molecular biology of gut and lung M cells for the first time. We will elucidate how they develop, are regulated and function at a molecular level, and how M cells maintain normal gut and lung tissues and induce immune responses to protect against microbial challenges. In the future, the new insights will be essential pre-requisites for the development of mucosal-based intervent ....New guardians of the mucosa: Molecular characterisation of M cell biology. We aim to completely define the cellular and molecular biology of gut and lung M cells for the first time. We will elucidate how they develop, are regulated and function at a molecular level, and how M cells maintain normal gut and lung tissues and induce immune responses to protect against microbial challenges. In the future, the new insights will be essential pre-requisites for the development of mucosal-based interventions and vaccines that protect the gut and lung from infectious and inflammatory issues. The harnessing of effective immune responses to control such challenges, are of enormous fundamental and long-standing biological interest, and are amongst the most important areas of current scientific research.Read moreRead less