A unified model of amino acid homeostasis. This project aims to develop a unified model of amino acid homeostasis in mammalian cells and apply it to brain cells. The model will be underpinned by a mathematical algorithm that allows predicting amino acid levels in the cytosol based on fundamental parameters such as transport and metabolism. This project should provide the significant benefit of enabling the prediction of essential functions such as cell growth and survival.
Molecular interactions in cell membranes. Cell membranes are a complex composite of proteins and lipids and we have only a rough idea about how they perform their many functions. Together with Leica Microsystems, this project will develop a new microscope that can map the molecular interactions within the membrane revealing details that have never been seen before.
Investigation of novel mechanisms for the regulation of sperm-oocyte interactions. Through work with national and international collaborators, this project aims to provide unprecedented insights into how spermatozoa recognise and bind to an oocyte. The approach is based on strong preliminary data indicating that molecular chaperones play a key role in the functional remodelling of the spermatozoon by promoting the assembly of multimeric oocyte receptor complexes. Through the use of state-of-the ....Investigation of novel mechanisms for the regulation of sperm-oocyte interactions. Through work with national and international collaborators, this project aims to provide unprecedented insights into how spermatozoa recognise and bind to an oocyte. The approach is based on strong preliminary data indicating that molecular chaperones play a key role in the functional remodelling of the spermatozoon by promoting the assembly of multimeric oocyte receptor complexes. Through the use of state-of-the-art cell biology and proteomic technologies, the project aims to investigate how molecular chaperones orchestrate these changes and in doing so, improve understanding of the fertilisation cascade and open up new contraceptive strategies.Read moreRead less
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
Initial Interactions Of Herpes Simplex Virus With Innate Immune Cells In Human Skin
Funder
National Health and Medical Research Council
Funding Amount
$522,589.00
Summary
Herpes simplex viruses 1 and 2 cause widespread and occasionally serious diseases including genital herpes, neonatal death and encephalitis. Current vaccine candidates are at best partially effective. This grant will examine the way that the virus enters, initially spreads within the skin and interacts with immune cells to help determine which cells should be stimulated by vaccines.
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.
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.
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
Discovery Early Career Researcher Award - Grant ID: DE240101055
Funder
Australian Research Council
Funding Amount
$448,737.00
Summary
How blood vessel stiffness regulates their growth and maintenance. This project aims to reveal an unidentified molecular mechanism of how endothelial cells in the walls of blood vessels detect stiffness of the surrounding environment in order to regulate blood vessel growth and maintenance. The results are expected to advance the emerging field of mechanobiology by combining cutting-edge cell biology and microscopy techniques carried out in novel 3D cell culture and unique quail models. The bene ....How blood vessel stiffness regulates their growth and maintenance. This project aims to reveal an unidentified molecular mechanism of how endothelial cells in the walls of blood vessels detect stiffness of the surrounding environment in order to regulate blood vessel growth and maintenance. The results are expected to advance the emerging field of mechanobiology by combining cutting-edge cell biology and microscopy techniques carried out in novel 3D cell culture and unique quail models. The benefits of these outcomes include generation of knowledge on the impact of tissue stiffness on the signalling mechanisms that drive formation and maintenance of blood vessels. In the long term, this fundamental understanding could give rise to major developments in emerging industries such as organ bioengineering.Read moreRead less
Sensing biomechanical forces in the heart. Mechanosensitive ion channels are key molecules that define how each heart cell interacts with their physical environment. Yet how they enable cells to decode biomechanical cues remains poorly understood. At the heart of this problem is a lack of tools to quantify the force required for activation. This project aims to develop novel technologies to record the activity of these essential channels in a critical cell type within the heart, and use this inf ....Sensing biomechanical forces in the heart. Mechanosensitive ion channels are key molecules that define how each heart cell interacts with their physical environment. Yet how they enable cells to decode biomechanical cues remains poorly understood. At the heart of this problem is a lack of tools to quantify the force required for activation. This project aims to develop novel technologies to record the activity of these essential channels in a critical cell type within the heart, and use this information in addition to micro-engineering approaches to fully understand the role of these channels in force sensing and generation, at both the single cell and micro-tissue levels. This knowledge and technology has broad utility that extends far beyond cardiac biology into multiple fields.Read moreRead less