Investigation of the mechanisms underlying successful placentation. The overall aim of this project is to provide novel insights into the basic cellular processes that underpin placental development and to improve our ability to manipulate mammalian reproduction, both human and animal. The placenta is critical for intrauterine development because it determines the level of nutrition, oxygenation and maternal tolerance to the developing foetus. The project intends to explore the role of prorenin ....Investigation of the mechanisms underlying successful placentation. The overall aim of this project is to provide novel insights into the basic cellular processes that underpin placental development and to improve our ability to manipulate mammalian reproduction, both human and animal. The placenta is critical for intrauterine development because it determines the level of nutrition, oxygenation and maternal tolerance to the developing foetus. The project intends to explore the role of prorenin and its receptor as a novel mechanism driving placentation. Applications for expected project outcomes may include improved breeding of threatened animal species and economically valuable domestic animals as well as improved health care and fertility control for domesticated pets and feral animals. Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE210100011
Funder
Australian Research Council
Funding Amount
$900,000.00
Summary
Integrated Multimodal System for Multiplexed Imaging of Signal Transduction. This project will introduce a unique microscopy platform and associated technologies into the Australian research environment that will enable researchers to redefine our understanding of molecular signal transduction. The instrumentation will enable the multidimensional imaging of live cells with unprecendented speed and sensitivity. The featured imaging modalities will enable the integration of distinct biological, ....Integrated Multimodal System for Multiplexed Imaging of Signal Transduction. This project will introduce a unique microscopy platform and associated technologies into the Australian research environment that will enable researchers to redefine our understanding of molecular signal transduction. The instrumentation will enable the multidimensional imaging of live cells with unprecendented speed and sensitivity. The featured imaging modalities will enable the integration of distinct biological, biochemical and chemical probes with a focus on minimizing phototoxicity. Expected outcomes include new fundamental knowledge on molecular signal transduction and cell heterogeneity; development of novel probes and methodologies and the development of new and existing interdisciplinary research collaborations. Read moreRead less
Novel models to advance our understanding of mammalian development. This project aims to add to the understanding of cellular processes underpinning mammalian development. Protein phosphorylation is a dynamic process regulated by both protein kinases and protein phosphatases. While the role of kinases in cellular functions are well defined, the roles of protein phosphatases are not well understood. Using a range of laboratory models this project aims to discover the function of the phosphatase P ....Novel models to advance our understanding of mammalian development. This project aims to add to the understanding of cellular processes underpinning mammalian development. Protein phosphorylation is a dynamic process regulated by both protein kinases and protein phosphatases. While the role of kinases in cellular functions are well defined, the roles of protein phosphatases are not well understood. Using a range of laboratory models this project aims to discover the function of the phosphatase PP2A, in cell proliferation, survival, differentiation and DNA damage repair. The anticipated outcome is an improved understanding of all stages of mammalian development. This will provide significant benefits in the biotechnology, chemical and pharmaceutical industries.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE140100149
Funder
Australian Research Council
Funding Amount
$300,000.00
Summary
CyTOF platform for the Advanced Cytometry Facility: overcoming fluorescence spectral barriers to truly multiparametric cytometry by mass spectrometry. Cytometry by time-of-flight mass spectrometry platform for the Advanced Cytometry Facility: overcoming fluorescence spectral barriers to truly multiparametric cytometry by mass spectrometry: This project will provide a flow cytometer capable of analysing single cells by time-of-flight mass spectrometry. Antibody labels for cell components will ena ....CyTOF platform for the Advanced Cytometry Facility: overcoming fluorescence spectral barriers to truly multiparametric cytometry by mass spectrometry. Cytometry by time-of-flight mass spectrometry platform for the Advanced Cytometry Facility: overcoming fluorescence spectral barriers to truly multiparametric cytometry by mass spectrometry: This project will provide a flow cytometer capable of analysing single cells by time-of-flight mass spectrometry. Antibody labels for cell components will enable measurement of up to 100 parameters/cell. Developing analytical and modelling algorithms like Spanning tree Progression of Density normalised Events (SPADE), this project will aim to map the relationships of various unelucidated cell lineages, via functional pathway connections. New pathways thus revealed will enable elaboration and use of novel specific molecules in perturbational analyses to confirm and further enhance the understanding of these highly intricate, basic relationships. This will provide unparalleled insight, both into early development of stem cells and mechanisms of maintenance of homeostasis in differentiated cells.Read moreRead less
Imaging the T cell signalling machinery . The conversion of external stimuli to the interior of a cell is a fundamental process that underpins many unique facets of biology, including cellular movement, nerve transmission, response to hormones and immune recognition. However, the basic mechanism by which such signals are transmitted across cellular membranes is poorly understood. This proposal will seek to bridge this gap in our knowledge by imaging a multi-component “decision-making” machine th ....Imaging the T cell signalling machinery . The conversion of external stimuli to the interior of a cell is a fundamental process that underpins many unique facets of biology, including cellular movement, nerve transmission, response to hormones and immune recognition. However, the basic mechanism by which such signals are transmitted across cellular membranes is poorly understood. This proposal will seek to bridge this gap in our knowledge by imaging a multi-component “decision-making” machine that controls whether or not the immune system becomes activated. Accordingly, this proposal will provide far-reaching insights into molecular events that are of central importance to the initiation of immunity, and thus will ultimately benefit society via improvements in health.Read moreRead less
Novel mechanisms of early growth response-1 activation through the epidermal growth factor receptor. This project will expand our knowledge of how cytokines and growth factors switch on signalling pathways from the cell surface to the nucleus. Unique antibodies will characterise regulatory routes, state-of-the-art microscopy will define dynamic patterns of receptor co-assembly, and in vivo studies will show receptor crosstalk in animal models.
DNA nanotechnology for controlled antigen presentation to T cells. The project aims to present individual antigens to T cells and to image T cell receptor signalling with single molecule microscopy. Combining DNA origami nanotechnology with single molecule imaging should reveal the sensitivity of T cell signalling. A DNA force sensor will determine whether mechanical forces contribute to antigen discrimination. The project will use the nanotechnology strategy to identify antigen-specific T cells ....DNA nanotechnology for controlled antigen presentation to T cells. The project aims to present individual antigens to T cells and to image T cell receptor signalling with single molecule microscopy. Combining DNA origami nanotechnology with single molecule imaging should reveal the sensitivity of T cell signalling. A DNA force sensor will determine whether mechanical forces contribute to antigen discrimination. The project will use the nanotechnology strategy to identify antigen-specific T cells in tissue. The project is expected to advance understanding of T cell biology, and contribute to DNA nanotechnology and super-resolution microscopy whilst providing fundamental insights into antigen recognition by T cells and ultimately derive clinically relevant practical applications.Read moreRead less
Life at the nanometre scale: imaging immunological synapses with a novel super-resolution fluorescence microscope. This project aims to image individual proteins in activated white blood cells in order to understand how lymphocytes participate in an immune response. The problem is that current imaging modalities either lack resolution or are unsuitable for live cell and three-dimensional (3D) imaging. With the project’s industry partner, Carl Zeiss MicroImaging, the project will build and apply ....Life at the nanometre scale: imaging immunological synapses with a novel super-resolution fluorescence microscope. This project aims to image individual proteins in activated white blood cells in order to understand how lymphocytes participate in an immune response. The problem is that current imaging modalities either lack resolution or are unsuitable for live cell and three-dimensional (3D) imaging. With the project’s industry partner, Carl Zeiss MicroImaging, the project will build and apply a novel microscope that is capable of visualising single proteins in 3D and live cells. This technology will provide insights into signalling and lymphocyte function on a true molecular scale.Read moreRead less
Nano-scale organisation of cellular adhesions. Cell migration is a key aspect of many normal processes but also of diseases such as cancers. This project will use a novel fluorescence microscope that can see single proteins to identify how cell adhesions are formed, remodelled and disassembled. This knowledge will help to design better drugs against cancers and novel implantable materials.
Discovery Early Career Researcher Award - Grant ID: DE130100251
Funder
Australian Research Council
Funding Amount
$375,000.00
Summary
Biophysical mechanisms regulating early T cell signalling events. T cell activation in response to foreign pathogens or cancer cells requires a complex set of protein interactions which must be controlled in space and time. This project will use new microscopy methods with single-molecule sensitivity to determine how the cell membrane and protein clustering regulate these interactions.