Dehydration and the natriuretic peptide system in the toad, Bufo marinus

The natriuretic peptide system is a family of related proteins that in humans function to reduce blood pressure and blood volume. However, in amphibians the function is less well understood. This thesis demonstrates that the amphibian, Bufo marinus, possesses a well-developed natriuretic peptide system that is capable of responding to changes induced by dehydration.

Natriuretic peptides : do they regulate water balance in desert-adapted rodents?

This research determined how the natriuretic peptide system, which controls water and salt balance, responds to water limitation in a desert rodent. It was found that a uniform down-regulation of the system is not part of the physiological response to minimise water loss during periods of low water availability.

Natriuretic peptide receptor signalling in the gills of fishes

Natriuretic peptide hormones exert their effects by binding to receptor proteins and activating cellular responses. Fish gills interface with the aquatic environment. Therefore, natriuretic peptide receptor activity in gills from marine and freshwater fishes was examined. The potencies of natriuretic peptides were compared and a novel cellular response was identified.

Mechanisms regulating the function of the ATP7B copper-ATPase

The copper-transporting ATP7B protein is defective in patients with Wilson disease, which causes the accumulation of toxic levels of copper in the body particularly in the liver. This thesis provides new information about how ATP7B maintains copper levels in the body within safe limits.

Mutation analysis of the Menkes gene

Menkes disease is a copper deficiency caused by mutations in the Menkes gene, which encodes a copper-transporting protein. This study identified the causative mutations in several Menkes patients, which provided a diagnostic test for relatives and identified critical regions of the Menkes protein. Further regions were identified through functional analysis of mutations introduced by in vitro mutagenesis.

Identification, distribution and expression of natriuretic peptide receptors in trout

This study identified cell receptors for trout natriuretic peptide hormone. These hormones protect the heart and maintain fluid balance. Receptor populations on cells depend on whether the animal lives in freshwater or saltwater. Receptors are widely distributed and different receptor types perform different tasks. Their original evolutionary role is suggested.

The role of ATP7A in copper homeostasis

Menkes disease is a fatal genetic copper deficiency. The Menkes protein (ATP7A) was found to remove copper from tissues in mice that expressed the human ATP7A. Promising results were obtained with the use of a new copper complex for treatment of Menkes disease using a mouse model.

Nitric oxide and vascular regulation in fishes and amphibians

Nitric oxide is an important molecule in the regulation of the cardiovascular system and blood pressure. This research provided new insights into the evolution of nitric oxide control of blood vessels by showing how nitric oxide signalling causes vasodilation in the circulation of amphibians and fishes.

Molecular biology of natriuretic peptides in reptiles and birds

The heart produces natriuretic peptides that are critical regulators of blood pressure and renal function. This study examined the molecular evolution of natriuretic peptides in vertebrates and discovered novel forms of the peptides in birds. The research outcomes advanced our knowledge of the importance of these peptides in animal physiology.

Evaluation of novel dairy fatty acids in inflammatory muscle-wasting conditions

This work examined the effects of a novel dairy fatty acid conjugated linoleic acid (CLA) and its effects on muscle wasting in advanced cancer. Results showed a positive anti-inflammatory role of CLA on the supression of tumour growth and established a model for studying the action of CLA in human muscle-wasting conditions.

Evolution of class I cytokine receptor signalling

Cytokines are proteins that provide essential signals to blood and immune cells. The evolution of this system was determined from primitive organisms to humans and zebrafish. Analysis of zebrafish granulocyte colony-stimulating factor (GCSF) signalling revealed broad conservation of function with mammals and a novel role in white blood cell migration.

Natriuretic peptide regulation of the kidney and urinary bladder in the cane toad, Bufo marinus

The natriuretic peptide system of mammals is important in the control of blood volume but its function in non-mammalian animals is unclear. This study identified a functional natriuretic peptide system in an amphibian and showed that the hormones are involved in the control of fluid balance.