The recirculation of myeloid dendritic cells. This project aims to understand dendritic cell recirculation. It will use virological tools to track dendritic cell migration, and identify key decision points. Expected outcomes include enhanced capacity in basic research and greater interdisciplinary collaboration between virology and immunology research groups. Significant benefits will include a new understanding of how G protein coupled receptor signalling and other tissue cues guide dendritic c ....The recirculation of myeloid dendritic cells. This project aims to understand dendritic cell recirculation. It will use virological tools to track dendritic cell migration, and identify key decision points. Expected outcomes include enhanced capacity in basic research and greater interdisciplinary collaboration between virology and immunology research groups. Significant benefits will include a new understanding of how G protein coupled receptor signalling and other tissue cues guide dendritic cell recirculation, and what consequences the recirculation has for immune cell function. This understanding will significantly advance our basic understanding of the immune system.Read moreRead less
Is FGF21 the master regulator of protein intake? The project plans to bring together two major, rapidly growing disciplines – nutritional geometry and metabolic signalling – to address a topic of fundamental biological significance: the regulation of protein intake. A specific capacity to regulate protein intake has been shown for organisms spanning slime moulds to humans, yet the controlling mechanisms remain elusive. The project aims to test the hypothesis that fibroblast growth factor 21, rel ....Is FGF21 the master regulator of protein intake? The project plans to bring together two major, rapidly growing disciplines – nutritional geometry and metabolic signalling – to address a topic of fundamental biological significance: the regulation of protein intake. A specific capacity to regulate protein intake has been shown for organisms spanning slime moulds to humans, yet the controlling mechanisms remain elusive. The project aims to test the hypothesis that fibroblast growth factor 21, released from the liver under low protein nutrition, is a master regulator of protein intake. Understanding the mechanisms of protein appetite may have implications for organismal biology, understanding social interactions, the structure of food webs and the health and welfare of food and companion animals and humans.Read moreRead less
Regenerating lizard tails: A model for understanding the process of lymphangiogenesis. In humans, impaired lymphatic drainage in limbs causes the debilitating swelling termed lymphoedema. Lymphoedema affects 500,000,000 people worldwide. In the developed world lymphoedema predominantly results from surgery for cancer, and occurs in approximately 25% of breast cancer patients. We will examine lymph vessel regeneration (lymphangiogenesis) in a naturally regenerating, complex structure (the lizard ....Regenerating lizard tails: A model for understanding the process of lymphangiogenesis. In humans, impaired lymphatic drainage in limbs causes the debilitating swelling termed lymphoedema. Lymphoedema affects 500,000,000 people worldwide. In the developed world lymphoedema predominantly results from surgery for cancer, and occurs in approximately 25% of breast cancer patients. We will examine lymph vessel regeneration (lymphangiogenesis) in a naturally regenerating, complex structure (the lizard tail), to describe the regrowth process and determine the abundance, location, functional properties and molecular control of the new lymphatics. Furthermore, if reptilian lymphatic growth factors can promote lymphangiogenesis in mammals, we can design novel therapeutic approaches using reptilian ligands to promote lymphangiogenesis in lymphoedematous human tissues.Read moreRead less
Adaptation of respiratory chemoreception: role of inhibitory neuropeptides. The project aims to investigate how the retrotrapezoid nucleus (RTN) is involved in respiratory adaptation to hypercapnia. Chemoreceptor neurons in the RTN are crucial for life however, the mechanisms that underlie their basal and stimulated activity, to control breathing, remain to be clarified. This project will investigate the role of galanin in RTN-mediated regulation of breathing. The project looks to determine inst ....Adaptation of respiratory chemoreception: role of inhibitory neuropeptides. The project aims to investigate how the retrotrapezoid nucleus (RTN) is involved in respiratory adaptation to hypercapnia. Chemoreceptor neurons in the RTN are crucial for life however, the mechanisms that underlie their basal and stimulated activity, to control breathing, remain to be clarified. This project will investigate the role of galanin in RTN-mediated regulation of breathing. The project looks to determine instructive and multifunctional roles of peptidergic chemosensory neurons and their contribution to local inhibitory control of the respiratory network. New knowledge from the project may in the future assist translational research into respiratory disorders and lead to technological advances.Read moreRead less
Epigenetic Regulation of Fetal and Placental Development. Perturbations of the environment of the early embryo can alter fetal and placental growth. The mechanisms by which the early environment alters development of the fetal adrenal-placental axis are unknown. This axis coordinates fetal growth and development to ensure a successful transition from intra- to extrauterine life. We propose a novel role for the epigenetic regulation of imprinted genes in the activation of the fetal adrenal and in ....Epigenetic Regulation of Fetal and Placental Development. Perturbations of the environment of the early embryo can alter fetal and placental growth. The mechanisms by which the early environment alters development of the fetal adrenal-placental axis are unknown. This axis coordinates fetal growth and development to ensure a successful transition from intra- to extrauterine life. We propose a novel role for the epigenetic regulation of imprinted genes in the activation of the fetal adrenal and in placental growth and differentiation. This proposal extends the 'genetic conflict' hypothesis of the role of imprinted genes beyond its current focus on the regulation of fetal nutrient supply and demand.Read moreRead less
The Immunoregulatory Role of the Endogenous Cannabinoid Anandamide. Anandamides are naturally occurring fatty acids that act at the cannabinoid receptor expressed in the brain and periphery. A new proposal by our research group challenges traditional models of the disease process by suggesting that the anandamide system is an important imunoregulatory system that can be targeted by invading pathogens. We propose that disruption to the anandamide system, by bacteria or viruses acting at the rece ....The Immunoregulatory Role of the Endogenous Cannabinoid Anandamide. Anandamides are naturally occurring fatty acids that act at the cannabinoid receptor expressed in the brain and periphery. A new proposal by our research group challenges traditional models of the disease process by suggesting that the anandamide system is an important imunoregulatory system that can be targeted by invading pathogens. We propose that disruption to the anandamide system, by bacteria or viruses acting at the receptor to block immunological responses, contributes to chronic illness states. At this point we have good evidence that anandamides are immunoregulators, however, we have very little knowledge of their precise physiological role. The aim of this research is to begin to characterise the immunoregulatory role of the anandamide system. This project will provide a comprehensive understanding of this endogenous control system, the immunological properties of which have not previously been described. The outcome of this research may lead to the identification of new avenues for the development of pharmaceutical interventions that can target this system.Read moreRead less
Evolution of sound localisation in vertebrates: head size, sound frequency and neural phase-locking. Hearing is our most important sense for interpersonal communication, yet we have a fragmentary understanding of the basic mechanisms involved in normal hearing. This project addresses the question of how sound location is represented in the brain through the processing of minute time difference with which sounds reach the two ears. The outcome will ultimately enable us to infer how the human brai ....Evolution of sound localisation in vertebrates: head size, sound frequency and neural phase-locking. Hearing is our most important sense for interpersonal communication, yet we have a fragmentary understanding of the basic mechanisms involved in normal hearing. This project addresses the question of how sound location is represented in the brain through the processing of minute time difference with which sounds reach the two ears. The outcome will ultimately enable us to infer how the human brain localises sound, with practical applications for improved virtual auditory realities and hearing aids.Read moreRead less
Does muscle contribute to the maintenance of vitamin D status in winter? This project aims to test the mechanism by which vitamin D status is maintained in winter when input is low. The long half-life in blood of the vitamin D metabolite, 25-hydroxyvitamin D [25(OH)D], maintains an adequate vitamin D status over winter, when sunlight, which produces vitamin D in skin, is reduced. From preliminary data in sheep and mice, this project proposes that skeletal muscle, not fat, stores vitamin D. This ....Does muscle contribute to the maintenance of vitamin D status in winter? This project aims to test the mechanism by which vitamin D status is maintained in winter when input is low. The long half-life in blood of the vitamin D metabolite, 25-hydroxyvitamin D [25(OH)D], maintains an adequate vitamin D status over winter, when sunlight, which produces vitamin D in skin, is reduced. From preliminary data in sheep and mice, this project proposes that skeletal muscle, not fat, stores vitamin D. This project will test this hypothesis in sheep, cultured muscle cells and in transgenic mice. The project will confirm whether the processes identified in skeletal muscle contribute to the maintenance of vitamin D status, and identify ways of enhancing this process.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
Neurons and neurotransmitters that control the apnoeic response to irritation of the larynx. Normal function of the larynx enables breathing, cough, singing, speech and many other normal functions. This project will reveal how nerves in the brain coordinate to achieve these many functions; in particular the way that breathing stops if fluid or smoke enters the larynx.