Gastrointestinal hormones: linking insulin dysregulation and laminitis. This project aims to identify the earliest pathogenic factors of disease by investigating two key hormones, ghrelin and GLP-2, and whether a specific genetic mutation underlies insulin dysregulation. Using innovative approaches the project will enable the identification of at-risk animals and pinpoint novel treatment strategies. In the long term improved disease treatment and prevention will reduce the suffering associated w ....Gastrointestinal hormones: linking insulin dysregulation and laminitis. This project aims to identify the earliest pathogenic factors of disease by investigating two key hormones, ghrelin and GLP-2, and whether a specific genetic mutation underlies insulin dysregulation. Using innovative approaches the project will enable the identification of at-risk animals and pinpoint novel treatment strategies. In the long term improved disease treatment and prevention will reduce the suffering associated with painful and often lethal co-morbidities.Read moreRead less
Characterisation of bone and bone marrow resident tissue macrophages. This project aims to elucidate the identities of tissue macrophages involved in bone and blood system (bone marrow) homeostasis and function, and the molecular signatures underpinning their functional specialisation. It will then investigate whether decline in the function of these specialised macrophages occurs during skeletal and blood system ageing. Both skeletal and blood system decline contribute to age-associated loss of ....Characterisation of bone and bone marrow resident tissue macrophages. This project aims to elucidate the identities of tissue macrophages involved in bone and blood system (bone marrow) homeostasis and function, and the molecular signatures underpinning their functional specialisation. It will then investigate whether decline in the function of these specialised macrophages occurs during skeletal and blood system ageing. Both skeletal and blood system decline contribute to age-associated loss of productivity, and paralleled decline in the resident macrophages in these organs may be a common ageing mechanism. Demonstration that altered macrophage biology unpins decline in blood and bone may prolong peak health and increase productivity in the ageing population.Read moreRead less
Physiological activation and targets of calcium signaling in muscle. The skeletal muscle fibre is a highly specialised cell for the rapid delivery of calcium to elicit contraction, required for posture, movement and thus one's independence. Calcium is also a signal for other purposes, such as triggering other processes within the muscle for its own maintenance. These calcium signals are poorly understood. This project aims to determine when the calcium signals are turned on during normal muscle ....Physiological activation and targets of calcium signaling in muscle. The skeletal muscle fibre is a highly specialised cell for the rapid delivery of calcium to elicit contraction, required for posture, movement and thus one's independence. Calcium is also a signal for other purposes, such as triggering other processes within the muscle for its own maintenance. These calcium signals are poorly understood. This project aims to determine when the calcium signals are turned on during normal muscle activity and what the end result of the signals is for the muscle.Read moreRead less
Signalling cross-talk through Suppressors Of Cytokine Signalling (SOCS) initiates luteolysis in the ovary. Members of the newly discovered SOCS protein family block cytokine signal transduction pathways, including those for prolactin and GH. We have discovered that one of these proteins, SOCS-3, is upregulated in the corpus luteum of the ovary by prostaglandins and propose that induction of prolactin or GH resistance is a hitherto unrecognised and critical step in luteolysis. We have also disco ....Signalling cross-talk through Suppressors Of Cytokine Signalling (SOCS) initiates luteolysis in the ovary. Members of the newly discovered SOCS protein family block cytokine signal transduction pathways, including those for prolactin and GH. We have discovered that one of these proteins, SOCS-3, is upregulated in the corpus luteum of the ovary by prostaglandins and propose that induction of prolactin or GH resistance is a hitherto unrecognised and critical step in luteolysis. We have also discovered that this cross-talk between prostaglandin- and cytokine-receptor signalling pathways occurs in preadipocyte and breast cell lines and propose that this research will serve as a paradigm for understanding how sensitivity to cytokines can be controlled at a molecular level.Read moreRead less
Single vesicle dynamics and the control of secretion. This project investigates secretion and tests a new model for secretory control. Its outcomes will further our knowledge in this important area and may be significant in the longer term for the treatment of secretory diseases.
Muscle fibre excitability and calcium regulation in skeletal muscle of amphibians and mammals. The fundamental role of skeletal muscle is posture and movement. Essential for this is a specialised cell structure and a complex regulation of function. This project will define key aspects of muscle structure and functional regulation crucial to developing targets for improving function under stressed states such as fatigue, disease and age.
Calcium regulation in the skeletal muscle triad and along the fibre. The fundamental role of skeletal muscle is posture and movement. Alterations in the normal way calcium regulates skeletal muscle function in fatigue, age and disease states causes loss of normal function. Preventing or controlling these changes is a key therapeutic aim. However, we currently lack full understanding of key mechanisms of calcium regulation in healthy skeletal muscle. This project will define key aspects of cal ....Calcium regulation in the skeletal muscle triad and along the fibre. The fundamental role of skeletal muscle is posture and movement. Alterations in the normal way calcium regulates skeletal muscle function in fatigue, age and disease states causes loss of normal function. Preventing or controlling these changes is a key therapeutic aim. However, we currently lack full understanding of key mechanisms of calcium regulation in healthy skeletal muscle. This project will define key aspects of calcium regulation that could be crucial to developing targets for improving function of skeletal muscle under stressed states.Read moreRead less
Calcium cycling and heat generation in skeletal muscle fibres. This project aims to uncover the mechanisms that enable mammalian skeletal muscle to play a major role in generating the heat required to maintain a constant body temperature. The ability to modulate body heat played a defining role in the evolution of species, their behaviour and global distribution. How heat production occurs in resting muscle is of fundamental importance and will be defined for the first time, providing new avenu ....Calcium cycling and heat generation in skeletal muscle fibres. This project aims to uncover the mechanisms that enable mammalian skeletal muscle to play a major role in generating the heat required to maintain a constant body temperature. The ability to modulate body heat played a defining role in the evolution of species, their behaviour and global distribution. How heat production occurs in resting muscle is of fundamental importance and will be defined for the first time, providing new avenues to manipulate metabolic rate and counter obesity.Read moreRead less
Saving your skin: physiology of immune regulation in mammalian lymph nodes. The overall aim of this proposal is to understand the mechanisms through which a rare population of regulatory cells maintains skin integrity. Despite their importance, little is known about the regulatory pathways these cells utilise. Previous work from the team has described an innovative technique to enrich these cells for in-depth study and demonstrated their potent regulatory capacity in vivo. This project will enha ....Saving your skin: physiology of immune regulation in mammalian lymph nodes. The overall aim of this proposal is to understand the mechanisms through which a rare population of regulatory cells maintains skin integrity. Despite their importance, little is known about the regulatory pathways these cells utilise. Previous work from the team has described an innovative technique to enrich these cells for in-depth study and demonstrated their potent regulatory capacity in vivo. This project will enhance our understanding of these cells and uncover their mechanisms of action. The outcomes of this work will therefore provide fundamental new knowledge of skin physiology, and lead to novel insights regarding how healthy skin, which is essential for the very survival and function of a living organism, may be maintained.Read moreRead less
Deciphering novel control mechanisms in the skin. The overall aim of this project is to understand the cellular mechanisms that maintain skin integrity, and in particular, the role of a novel population of regulatory cells in mediating this process. This is important for our understanding of fundamental physiological interactions in the skin. The proposed research aims to uncover essential new information regarding a recently discovered population of regulatory cells, with particular respect to ....Deciphering novel control mechanisms in the skin. The overall aim of this project is to understand the cellular mechanisms that maintain skin integrity, and in particular, the role of a novel population of regulatory cells in mediating this process. This is important for our understanding of fundamental physiological interactions in the skin. The proposed research aims to uncover essential new information regarding a recently discovered population of regulatory cells, with particular respect to understanding their mechanisms of action. The outcomes of this work should provide fundamental new knowledge of skin physiology and lead to novel insights regarding how skin integrity may be maintained following the disruption of homeostasis mechanisms.Read moreRead less