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
The molecular basis for efficacy at G protein coupled receptors. This project aims to investigate the molecular steps underlying the relationship between sensing by signal-transmitting proteins on the cell surface called G protein-coupled receptors and cellular response. The project aims to build on studies that have sought to understand the primary, molecular basis for this cellular volume control. This project seeks to use these novel approaches to fill this knowledge gap, providing a deeper u ....The molecular basis for efficacy at G protein coupled receptors. This project aims to investigate the molecular steps underlying the relationship between sensing by signal-transmitting proteins on the cell surface called G protein-coupled receptors and cellular response. The project aims to build on studies that have sought to understand the primary, molecular basis for this cellular volume control. This project seeks to use these novel approaches to fill this knowledge gap, providing a deeper understanding of how physiology and medicines work. The project expects to expand fundamental understanding of signal transmission at this receptor class. This project will deliver benefits including expanded basic knowledge and a contribution to future improvements in drug development.Read moreRead less
A humanised sensory neuron high-throughput screening platform . Sensory neurons are responsible for converting external stimuli such as touch or temperature into graded electrical signals that allow us to interact with the world around us. However, unlike other cell types, sensory neurons cannot proliferate and thus must be removed from human cadavers, or animals, in order to study their pharmacology and function. This limits our ability to understand neuronal signalling pathways. This project a ....A humanised sensory neuron high-throughput screening platform . Sensory neurons are responsible for converting external stimuli such as touch or temperature into graded electrical signals that allow us to interact with the world around us. However, unlike other cell types, sensory neurons cannot proliferate and thus must be removed from human cadavers, or animals, in order to study their pharmacology and function. This limits our ability to understand neuronal signalling pathways. This project aims to use sensory neurons derived from human stem cells to develop and optimise assays that can be used to study the pharmacology and function of human sensory neurons in vitro. This enhances access to critical model systems and technology platforms and removes the need for isolation of cells from cadavers. 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
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
Defining mechanisms behind the formation of hierarchical vascular networks. Blood vessels form complex branched networks composed of arteries, capillaries and veins. The development and maintenance of different vessel systems (arteries and veins) is dependent on cell adherence properties within each vessel, yet how these are established and maintained remains unknown. This project aims to analyse the differences in junctional dynamics between sprouting arteries and veins, and to identify arteria ....Defining mechanisms behind the formation of hierarchical vascular networks. Blood vessels form complex branched networks composed of arteries, capillaries and veins. The development and maintenance of different vessel systems (arteries and veins) is dependent on cell adherence properties within each vessel, yet how these are established and maintained remains unknown. This project aims to analyse the differences in junctional dynamics between sprouting arteries and veins, and to identify arterial and venous signalling networks that make and maintain vessel identity. This project will reveal how adhesiveness is regulated in order to make a hierarchical, functional vascular network, with implications for engineering of functional, vascularised organs in the biotech sector.Read moreRead less