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Physiology of oxygen transport in the mammalian kidney. This project aims to improve understanding of oxygen regulation in renal tissue and knowledge of the physiology of the kidney. The mammalian kidney receives more oxygen than it uses or needs, and yet renal tissue is commonly found to be hypoxic. This project proposes that oxygen transport to the renal tissue is limited by blood vessel surface area. The project expects to generate anatomical data currently missing from the renal physiology c ....Physiology of oxygen transport in the mammalian kidney. This project aims to improve understanding of oxygen regulation in renal tissue and knowledge of the physiology of the kidney. The mammalian kidney receives more oxygen than it uses or needs, and yet renal tissue is commonly found to be hypoxic. This project proposes that oxygen transport to the renal tissue is limited by blood vessel surface area. The project expects to generate anatomical data currently missing from the renal physiology community, and potentially change the accepted story of oxygen homeostasis in the kidney. This will provide significant benefits, such as the provision of the foundational physiological science behind a determinant of kidney health and its flow-on impact to quality of life.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
Defining how serotonin regulates gut motility. This project aims to deepen knowledge of gastrointestinal physiology, and reveal the mechanisms by which the major gastrointestinal signalling molecule, serotonin, regulates gut peristalsis. Almost all of the serotonin in our body is made in the gastrointestinal tract where it controls many functions, including how our gut wall contracts during peristalsis. Proper control of gut peristalsis and the transit of material through our bowel is important ....Defining how serotonin regulates gut motility. This project aims to deepen knowledge of gastrointestinal physiology, and reveal the mechanisms by which the major gastrointestinal signalling molecule, serotonin, regulates gut peristalsis. Almost all of the serotonin in our body is made in the gastrointestinal tract where it controls many functions, including how our gut wall contracts during peristalsis. Proper control of gut peristalsis and the transit of material through our bowel is important for our health. This project expects to define how serotonin controls peristalsis, where in the bowel this serotonin comes from, how serotonin communicates with the nervous system in our gastrointestinal tract, and how the cells that synthesise gut serotonin respond to contraction to trigger the secretion of serotonin.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
Unified framework of intestinal motility. The project aims to establish how a few fundamental mechanisms determine the large repertoire of intestinal motor patterns responsible for moving nutrients along the digestive tract. The project will combine experimental and theoretical data, with biomechanical and electrophysiological models to create a new understanding of this essential function of the body.
Design of the cardiovascular system of living and fossil vertebrates. This project aims to understand how the heart and blood vessels evolved in mammals, birds, reptiles and fish to achieve efficiency. The heart is the most important organ for life. The project will study the structure and function of vertebrate animals’ hollow and spongy hearts to show how energetics shaped their evolution. It will measure arterial holes in bone to gauge brain and bone metabolism, which opens up a new way to me ....Design of the cardiovascular system of living and fossil vertebrates. This project aims to understand how the heart and blood vessels evolved in mammals, birds, reptiles and fish to achieve efficiency. The heart is the most important organ for life. The project will study the structure and function of vertebrate animals’ hollow and spongy hearts to show how energetics shaped their evolution. It will measure arterial holes in bone to gauge brain and bone metabolism, which opens up a new way to measure metabolism in extinct animals directly from fossils, rather than by inference from living relatives. The expected outcome is to correlate cardiovascular design and metabolic rates of organs.Read moreRead less
Matching of gas exchanger structure and function with activity and environment in air-breathing fishes. This project will investigate the physiology and structure of Australian fishes that use gills and breathe air. It will measure the partitioning of oxygen and carbon dioxide exchange between the aquatic (gills) and aerial (lung, swim-bladder or mouth) respiratory organs, in relation to dissolved oxygen in the water and metabolic energy demands by the fish. Rates of gas exchange, biochemical ....Matching of gas exchanger structure and function with activity and environment in air-breathing fishes. This project will investigate the physiology and structure of Australian fishes that use gills and breathe air. It will measure the partitioning of oxygen and carbon dioxide exchange between the aquatic (gills) and aerial (lung, swim-bladder or mouth) respiratory organs, in relation to dissolved oxygen in the water and metabolic energy demands by the fish. Rates of gas exchange, biochemical characteristics of the blood, anatomy and physiology of the exchange organs, and respiratory/locomotory coupling will be measured in three selected species during graded exercise. The results will help us understand the factors influencing the evolution of air-breathing.Read moreRead less
Skeletal endocrine signalling in the regulation of glucose metabolism. This project seeks to explore a highly novel and interesting recent development in bone biology: the fact that the skeleton is a central regulator of glucose metabolism. Currently, the mechanisms involved in this process remain unclear. mTORC1 has been identified as a signalling pathway in bone cells that modulates glucose metabolism. This project plans to selectively delete mTORC1 in the bone cells of mice to examine how ske ....Skeletal endocrine signalling in the regulation of glucose metabolism. This project seeks to explore a highly novel and interesting recent development in bone biology: the fact that the skeleton is a central regulator of glucose metabolism. Currently, the mechanisms involved in this process remain unclear. mTORC1 has been identified as a signalling pathway in bone cells that modulates glucose metabolism. This project plans to selectively delete mTORC1 in the bone cells of mice to examine how skeletal mTORC1 signalling regulates glucose metabolism, and identify novel pathways and circulating factors involved in this process. These studies may provide greater understanding of the basic biology of glucose metabolism, and may have applications in animal husbandry and the future management of diabetes.Read moreRead less
Environmental Control of Developmental Plasticity of Vertebrate Cardio-Pulmonary Systems. Our research will generate the first comprehensive picture of how environmental conditions are transduced to control the development of the vertebrate respiratory and cardiovascular systems over the perinatal period. The research will demonstrate how physiological systems are modified and hence evolve. Moreover, understanding the developmental pathology in embryos induced by changing environmental condition ....Environmental Control of Developmental Plasticity of Vertebrate Cardio-Pulmonary Systems. Our research will generate the first comprehensive picture of how environmental conditions are transduced to control the development of the vertebrate respiratory and cardiovascular systems over the perinatal period. The research will demonstrate how physiological systems are modified and hence evolve. Moreover, understanding the developmental pathology in embryos induced by changing environmental conditions (especially exposure to steroid-like pollutants) is crucial to support breeding programs of endangered species and may improve veterinary and medicinal treatment of premature animals and humans. This multi-disciplinary, international collaboration provides an international training ground and two-way exchange of students and postdocs.Read moreRead less
Scaling of structure, function and energetics of the vertebrate cardiovascular system. The hearts of mammals, reptiles and fish do different amounts of work, depending on the animal’s metabolic rate and body size. This project attempts to understand why hearts are the size and thickness that they are, and whether this results in minimising the work necessary to satisfy the requirements of the animal.