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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.
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.
Cardiac a1-adrenergic receptors in survival of the fittest. This project aims to determine the role of alpha1A-adrenergic receptor inactivation, a receptor/signalling pathway, in mediating cardiac contraction and survival in response to stressors fight-or-flight response triggers.Higher organisms’ ability to respond to environmental changes is central to the survival of the fittest, and is mediated by the release of catecholamines that stimulate adrenergic receptors. The precise receptor and sig ....Cardiac a1-adrenergic receptors in survival of the fittest. This project aims to determine the role of alpha1A-adrenergic receptor inactivation, a receptor/signalling pathway, in mediating cardiac contraction and survival in response to stressors fight-or-flight response triggers.Higher organisms’ ability to respond to environmental changes is central to the survival of the fittest, and is mediated by the release of catecholamines that stimulate adrenergic receptors. The precise receptor and signalling pathways underlying these adaptive responses remain unclear. This project’s research could improve contractility, reduce cardiomyocyte death and define organismal adaptation to extreme environmental changes.Read moreRead less
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
Phage display derived antibody fragments for membrane protein research. Membrane proteins are key components of all living organisms and represent more than 50 per cent of all drug targets. This project will redefine the way membrane proteins are studied and will be highly beneficial to basic research, human disease and the biotechnology industry.
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
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.
Structure and function of human zinc transporter membrane proteins. The aim of this project is to create fundamental new knowledge on how important mammalian membrane proteins operate. Membrane proteins are key drug targets and are significantly under-represented in structural databases. The project plans to combine innovative membrane protein screening technology with gene expression, structural biology, biophysics and cell biology. The project outcomes may elucidate specific molecular mechanis ....Structure and function of human zinc transporter membrane proteins. The aim of this project is to create fundamental new knowledge on how important mammalian membrane proteins operate. Membrane proteins are key drug targets and are significantly under-represented in structural databases. The project plans to combine innovative membrane protein screening technology with gene expression, structural biology, biophysics and cell biology. The project outcomes may elucidate specific molecular mechanisms underpinning the essential biological process of zinc homeostasis.Read moreRead less
Why is the peribacteroid membrane transcription factor SAT1 required for legume nitrogen fixation and what is its role in other symbiotic systems? This project will investigate the functional activity of the plant membrane bound basic helix-loop-helix (bHLH) transcription factor SAT1 in both nitrogen fixing (Rhizobia) and phosphorus acquiring (Arbuscular Mycorrhizal) symbioses found in plants. The project will identify its regulation and downstream activities across both symbiosis using selected ....Why is the peribacteroid membrane transcription factor SAT1 required for legume nitrogen fixation and what is its role in other symbiotic systems? This project will investigate the functional activity of the plant membrane bound basic helix-loop-helix (bHLH) transcription factor SAT1 in both nitrogen fixing (Rhizobia) and phosphorus acquiring (Arbuscular Mycorrhizal) symbioses found in plants. The project will identify its regulation and downstream activities across both symbiosis using selected legumes and or cereals.Read moreRead less
Molecular mechanisms for copper trafficking across membranes. Copper is a trace metal that is essential for all forms of life, however it is toxic in excess. Tightly controlled protein-based metalloregulatory systems are responsible for copper uptake and homeostasis in all cells. Components of these systems are integral membrane transport proteins, which include the Ctr proteins that are solely responsible for copper uptake into eukaryotic cells. This project aims to define the molecular mechani ....Molecular mechanisms for copper trafficking across membranes. Copper is a trace metal that is essential for all forms of life, however it is toxic in excess. Tightly controlled protein-based metalloregulatory systems are responsible for copper uptake and homeostasis in all cells. Components of these systems are integral membrane transport proteins, which include the Ctr proteins that are solely responsible for copper uptake into eukaryotic cells. This project aims to define the molecular mechanisms by which the Ctr proteins transport copper across eukaryotic cell membranes, by solving their three-dimensional structures by X-ray crystallography.Read moreRead less