Novel ways of regulating epithelial transport. This project is intended to discover novel intracellular mechanisms that regulate the rate of ion transport by the lung, the gut and the kidney. It will not only provide new insights into how the body controls a process that is critical to animal life, but also provide new targets for the development of pharmaceuticals.
A molecular structure-function investigation of major membrane channels involved in olfactory transduction. Olfactory receptor neurons are extraordinarily-sensitive sensors for detecting minute concentrations of odorant molecules. This project aims to extend our previous studies of these specialised mammalian olfactory cells by using state-of-the art technologies: electrophysiology (patch-clamp) and molecular biology (site-directed-mutagenesis), to investigate how the molecular structure of the ....A molecular structure-function investigation of major membrane channels involved in olfactory transduction. Olfactory receptor neurons are extraordinarily-sensitive sensors for detecting minute concentrations of odorant molecules. This project aims to extend our previous studies of these specialised mammalian olfactory cells by using state-of-the art technologies: electrophysiology (patch-clamp) and molecular biology (site-directed-mutagenesis), to investigate how the molecular structure of their ion channels (selective protein pores) and receptors contribute to the odorant-induced generation of electrical activity, which mediates our sense of smell (olfaction). The project has specific relevance for understanding olfaction, as well as relevance for other sensory systems and other ion channels.Read moreRead less
A thermodynamic pathway to intracellular delivery. Cells transmit information through molecules. By delivering foreign molecules into cells, such as DNA and proteins, it is possible to engineer and reprogram cells just like a computer. This proposal aims to develop a novel microfluidic device for intracellular delivery. The device will work by exposing cells to rapid thermal shock to generate transient disruptions in cell membranes and thereby enable influx of foreign molecules into cells. To un ....A thermodynamic pathway to intracellular delivery. Cells transmit information through molecules. By delivering foreign molecules into cells, such as DNA and proteins, it is possible to engineer and reprogram cells just like a computer. This proposal aims to develop a novel microfluidic device for intracellular delivery. The device will work by exposing cells to rapid thermal shock to generate transient disruptions in cell membranes and thereby enable influx of foreign molecules into cells. To understand how the method can be optimized, the thermodynamic pathway of membrane disruption will be investigated at a single cell level. The methods and insights arising from this project could eventually lead to novel, patentable and lower-cost health technologies.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
Electric field effects on cochlear tissues. The project aims to solve the underlying biology of how electricity flows through the cochlear tissues, where and how electrical stimulation excites the auditory neurons, and what the effects of sustained electrical stimulation are on the nerve fibre growth and function. The research aims to show how electric fields can be controlled in the cochlea, and how auditory nerve fibres are affected at the cellular and molecular level. The long-term aim is to ....Electric field effects on cochlear tissues. The project aims to solve the underlying biology of how electricity flows through the cochlear tissues, where and how electrical stimulation excites the auditory neurons, and what the effects of sustained electrical stimulation are on the nerve fibre growth and function. The research aims to show how electric fields can be controlled in the cochlea, and how auditory nerve fibres are affected at the cellular and molecular level. The long-term aim is to utilise these findings to improve the control of neuronal excitability, for development of interfaces with the nervous system.Read moreRead less
Physiological significance of transient receptor potential (TRPC3) ion channels in the cochlea. The project seeks to discover the function of transient receptor potential (TRPC3) ion channels in the cochlea. Recent studies have suggested that these proteins, which are expressed by the sensory and neural cells, are key elements regulating sound transduction and neurotransmission. The new knowledge about the physiological processes underlying hearing that this work will provide, will significantl ....Physiological significance of transient receptor potential (TRPC3) ion channels in the cochlea. The project seeks to discover the function of transient receptor potential (TRPC3) ion channels in the cochlea. Recent studies have suggested that these proteins, which are expressed by the sensory and neural cells, are key elements regulating sound transduction and neurotransmission. The new knowledge about the physiological processes underlying hearing that this work will provide, will significantly benefit national and international translational research that seeks to develop systems for controlling the sensitivity of our senses, developing biosensors, interacting with neural networks and developing neural prostheses. International collaborators in this project have enabled development of new models, technology and research training opportunities.Read moreRead less
Phospholipids and kinases as regulators of epithelial sodium channels. The intracellular signalling pathways that will be identified in this project will facilitate the development of novel therapies for the many conditions in which the activity of epithelial sodium channels is abnormal. These include influenza, otitis media, high blood pressure and cystic fibrosis. It will also provide training for post-doctoral fellows and research students in a number of the key techniques in modern cellular ....Phospholipids and kinases as regulators of epithelial sodium channels. The intracellular signalling pathways that will be identified in this project will facilitate the development of novel therapies for the many conditions in which the activity of epithelial sodium channels is abnormal. These include influenza, otitis media, high blood pressure and cystic fibrosis. It will also provide training for post-doctoral fellows and research students in a number of the key techniques in modern cellular physiology.Read moreRead less
Inhibitory control of retinal sensitivity. We will determine how the nerve cells that carry information from the eye to the brain are always able to provide signals despite very different environments; daylight, fog and night. Knowledge of how nerve cells achieve this rapid learning is important for any understanding of brain function; it is fundamental if we are to develop machines that see or that help restore vision in humans. The project will provide the world's first look at the synaptic ph ....Inhibitory control of retinal sensitivity. We will determine how the nerve cells that carry information from the eye to the brain are always able to provide signals despite very different environments; daylight, fog and night. Knowledge of how nerve cells achieve this rapid learning is important for any understanding of brain function; it is fundamental if we are to develop machines that see or that help restore vision in humans. The project will provide the world's first look at the synaptic physiology that underpins all visual perception, helping to bring Australia back to the forefront of research in this field. This new collaboration between two successful researchers will attract top quality students and researchers from Australia and abroad and be published in major journals.Read moreRead less
Central Muscarinic Receptors as Novel Drug Targets for Parkinson's Disease and Schizophrenia. Psychiatric and neurodegenerative disorders such as schizophrenia and Parkinson's disease are linked to alterations in the activity of neurons in the brain containing the chemical dopamine. Other types of brain neurons containing the chemical acetylcholine regulate dopamine neuron activity by acting on acetylcholine receptors located on dopamine neurons. We aim to determine how these important recepto ....Central Muscarinic Receptors as Novel Drug Targets for Parkinson's Disease and Schizophrenia. Psychiatric and neurodegenerative disorders such as schizophrenia and Parkinson's disease are linked to alterations in the activity of neurons in the brain containing the chemical dopamine. Other types of brain neurons containing the chemical acetylcholine regulate dopamine neuron activity by acting on acetylcholine receptors located on dopamine neurons. We aim to determine how these important receptors regulate dopamine neuron activity using genetically modified mice deficient in acetylcholine receptors, together with newly developed physiological methods and new acetylcholine receptor drugs. These studies will foster the design of novel acetylcholine receptor drugs as effective pharmaceutical treatments of neurological and psychiatric disorders related to brain dopamine dysfunction.Read moreRead less
Muscarinic Receptor Regulation of Dopamine Reward Pathways in the Brain. Human disorders such as schizophrenia and drug addiction are linked to alterations in the activity of neurons in the brain containing the chemical dopamine. Other types of brain neurons containing the chemical acetylcholine regulate the activity of dopamine neurons by acting on acetylcholine receptors located on dopamine neurons. We aim to examine how dopamine neuron activity is regulated by these receptors using newly de ....Muscarinic Receptor Regulation of Dopamine Reward Pathways in the Brain. Human disorders such as schizophrenia and drug addiction are linked to alterations in the activity of neurons in the brain containing the chemical dopamine. Other types of brain neurons containing the chemical acetylcholine regulate the activity of dopamine neurons by acting on acetylcholine receptors located on dopamine neurons. We aim to examine how dopamine neuron activity is regulated by these receptors using newly developed physiological methods together with a new acetylcholine receptor drug. We also aim to assess the suitability of mice genetically modified to be deficient in acetylcholine receptors as animal models of dopamine dysfunction related to schizophrenia and drug addiction.Read moreRead less