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
An active ion transport pathway exploited by coronaviruses. Cells have active transport “pumps” that are regulators of a variety of cellular processes. This project aims to understand how a specific ion pump is exploited by coronaviruses when they infect animal cells. These studies will provide new mechanistic insights into how coronaviruses alter calcium signalling in cells and how a specific ion pump regulates a variety of key processes during coronavirus infection. This work will greatly enha ....An active ion transport pathway exploited by coronaviruses. Cells have active transport “pumps” that are regulators of a variety of cellular processes. This project aims to understand how a specific ion pump is exploited by coronaviruses when they infect animal cells. These studies will provide new mechanistic insights into how coronaviruses alter calcium signalling in cells and how a specific ion pump regulates a variety of key processes during coronavirus infection. This work will greatly enhance our understanding of the intersection between ion pumps and viruses.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
Phosphoinositide regulation of lysosome reformation during autophagy. This project aims to investigate a new critical step in the autophagy pathway, autophagic lysosome reformation, a fundamental, evolutionarily conserved mechanism for cellular homeostasis. By combining gene function studies with advanced cellular imaging techniques, this project will investigate the dynamic membrane changes that drive this lysosome recycling pathway and how it is regulated by a hierarchical succession of specif ....Phosphoinositide regulation of lysosome reformation during autophagy. This project aims to investigate a new critical step in the autophagy pathway, autophagic lysosome reformation, a fundamental, evolutionarily conserved mechanism for cellular homeostasis. By combining gene function studies with advanced cellular imaging techniques, this project will investigate the dynamic membrane changes that drive this lysosome recycling pathway and how it is regulated by a hierarchical succession of specific enzymes. The expected outcome will be to re-define the archetypical autophagy pathway and characterise novel mechanisms by which it is controlled. This project will reveal new fundamental biological processes, and act as a framework for developing new imaging modalities and tools for studying autophagy.Read moreRead less
Discovering novel allosteric probes of muscarinic acetylcholine receptors. This project aims at fostering novel approaches to selectively target vital receptors in the human body, the muscarinic acetylcholine receptors (mAChRs). By harnessing the design of receptor mutations, compounds synthesis and fluorescent imaging, the project expects to develop new pharmacological tools for a family of receptors essential for the life of all vertebrates. By enriching our understanding of this family of rec ....Discovering novel allosteric probes of muscarinic acetylcholine receptors. This project aims at fostering novel approaches to selectively target vital receptors in the human body, the muscarinic acetylcholine receptors (mAChRs). By harnessing the design of receptor mutations, compounds synthesis and fluorescent imaging, the project expects to develop new pharmacological tools for a family of receptors essential for the life of all vertebrates. By enriching our understanding of this family of receptor, the project expects to provide significant benefits to the research field by impacting on future drug discovery efforts, not only at mAChRs, but at other structurally related receptors.Read moreRead less
Mechanisms of itch - from endosomal signalling to neural circuits. This project aims to investigate the cellular and circuit mechanisms of itch transmission in the spinal cord by defining the activation and propagation of itch-specific signals. This project expects to generate new knowledge in the area of neuronal signalling and circuitry using novel electrophysiological approaches that target and manipulate specific nerves and cellular components. The project will characterise signalling within ....Mechanisms of itch - from endosomal signalling to neural circuits. This project aims to investigate the cellular and circuit mechanisms of itch transmission in the spinal cord by defining the activation and propagation of itch-specific signals. This project expects to generate new knowledge in the area of neuronal signalling and circuitry using novel electrophysiological approaches that target and manipulate specific nerves and cellular components. The project will characterise signalling within specific spinal subcircuits in order to understand the mechanisms of receptor activation and signalling, and investigate how circuit activity is regulated. This project expects to advance fundamental understanding of itch signalling in the nervous system and provide avenues for future therapeutics.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
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.
RhoA signaling: the nanoscale mechanisms of mechanochemical regulation. This project aims to elucidate a new paradigm for regulating cell signals at the nanoscale level. Cell signalling involves the coordination of multi-molecular networks at the plasma membrane, the interface between the cell and its external environment. These are often thought to involve the assembly of multimolecular complexes through the action of protein scaffolds. This project will focus on how the contractile regulator, ....RhoA signaling: the nanoscale mechanisms of mechanochemical regulation. This project aims to elucidate a new paradigm for regulating cell signals at the nanoscale level. Cell signalling involves the coordination of multi-molecular networks at the plasma membrane, the interface between the cell and its external environment. These are often thought to involve the assembly of multimolecular complexes through the action of protein scaffolds. This project will focus on how the contractile regulator, anillin, controls RhoA signalling by kinetic regulation. In particular, how nanoscale clustering of anillin by the dynamic actomyosin cytoskeleton modulates RhoA signalling for contractility and tissue homeostasis. The outcomes of this project are first and foremost fundamental understanding of how cells communicate with one another.Read moreRead less