Many Ys in monotremes: multiple sex chromosomes and sex determination in platypus and echidna. Platypus and Echidna are Australian icons, even featuring on our coins. Their unusual biology and ancient relationship to humans make them unique for understanding the mammalian genome, as demonstrated by our recent discovery of ten sex chromosomes in platypus that link mammal and bird sex. Still little is known about their genome, embryo development and how sex is determined. We will identify new gene ....Many Ys in monotremes: multiple sex chromosomes and sex determination in platypus and echidna. Platypus and Echidna are Australian icons, even featuring on our coins. Their unusual biology and ancient relationship to humans make them unique for understanding the mammalian genome, as demonstrated by our recent discovery of ten sex chromosomes in platypus that link mammal and bird sex. Still little is known about their genome, embryo development and how sex is determined. We will identify new genes on all ten sex chromosomes and investigate how they determine sex. The set up of an Australian Monotreme Resource Centre will be crucial for this research and attract worldwide high profile collaborations. We will answer important general questions in monotreme biology and contribute to our understanding of sexual abnormalities in humans.Read moreRead less
Single Minded 2: Cross coupling or specificity within the bHLH/PAS transcription factor family? Understanding the mechanisms of action of SIM2 may lead to novel ideas towards drug development for diseases such as Down syndrome and cancer. The SIM2 protein can interfere with activity of the related Hypoxia Inducible Factor (HIF), a protein important in stress response and recovery from stroke. Understanding the molecular basis of this interference could aid current strategies being used to manipu ....Single Minded 2: Cross coupling or specificity within the bHLH/PAS transcription factor family? Understanding the mechanisms of action of SIM2 may lead to novel ideas towards drug development for diseases such as Down syndrome and cancer. The SIM2 protein can interfere with activity of the related Hypoxia Inducible Factor (HIF), a protein important in stress response and recovery from stroke. Understanding the molecular basis of this interference could aid current strategies being used to manipulate HIF for pharmaceutical benefit.Read moreRead less
The genetic regulation of organogenesis: endoderm development in the Drosophila embryo. Embryonic development is an important research field in biology, not only for its extraordinary complexity but also because of the insights it provides into molecular processes that underpin a variety of diseases. This project aims to discover genes and molecules that regulate the normal development of one of the most important organs, the gut.
Plasticity of gastrointestinal vagal afferents. The aim of this project is to identify how leptin modulates specific subtypes of vagal afferent within the gut and the plasticity of this system under different dietary conditions. This proposed project will substantially increase understanding of the interactions between leptin, known to influence food intake, and vagal afferent satiety signals. It will also increase understanding of how these interactions alter in obesity and ultimately provide t ....Plasticity of gastrointestinal vagal afferents. The aim of this project is to identify how leptin modulates specific subtypes of vagal afferent within the gut and the plasticity of this system under different dietary conditions. This proposed project will substantially increase understanding of the interactions between leptin, known to influence food intake, and vagal afferent satiety signals. It will also increase understanding of how these interactions alter in obesity and ultimately provide targets and/or concepts for the pharmacotherapy of obesity.Read moreRead less
Central pathways regulating visceral pain. This project aims to investigate the neural pathways within the spinal cord and brain processing colorectal pain perception. The project aims to identify the spinal cord neurons relaying colorectal signalling into the brain and the influence of descending modulation from the brainstem upon these pathways. The outcomes will greatly benefit fundamental understanding of the central pathways processing visceral pain.
Function and redundancy of SOX genes in the mammalian sex determination pathway. We are studying a mouse model of abnormal sex organ development in which genetically female mice develop as males. Our basic research program will lead to greater understanding of the genetic switch controlling the formation of male and female characteristics. This research should in turn provide insight into the causes of defects in patients with disorders of sex development, helping to inform the difficult clinica ....Function and redundancy of SOX genes in the mammalian sex determination pathway. We are studying a mouse model of abnormal sex organ development in which genetically female mice develop as males. Our basic research program will lead to greater understanding of the genetic switch controlling the formation of male and female characteristics. This research should in turn provide insight into the causes of defects in patients with disorders of sex development, helping to inform the difficult clinical decisions that need to be made for their treatment, and ultimately leading to better management and therapeutic strategies. Our studies may also provide unique methods to control the exotic mouse population, using the daughterless strategy.Read moreRead less
Molecular mechanisms regulating Ca2+ channels formed by Orai and STIM proteins. Store-operated calcium channels play a central role in the functions of all animal cells. They participate in generating the cellular responses to hormones, antigens, growth factors and other physiological stimuli. The aims of this project are to elucidate cellular mechanisms that regulate interaction between the molecular components of store-operated calcium channel, Orai and STIM. Using techniques of electrophysiol ....Molecular mechanisms regulating Ca2+ channels formed by Orai and STIM proteins. Store-operated calcium channels play a central role in the functions of all animal cells. They participate in generating the cellular responses to hormones, antigens, growth factors and other physiological stimuli. The aims of this project are to elucidate cellular mechanisms that regulate interaction between the molecular components of store-operated calcium channel, Orai and STIM. Using techniques of electrophysiology and molecular biology we expect to answer a fundamental question how STIM and Orai proteins interact to form functional store-operated calcium channels, and how the expression of STIM and Orai is regulated.Read moreRead less
Cellular bases of enteric neural circuitry underlying gut propulsion. This project aims to investigate the neural bases of behaviour in the mammalian gut. The Enteric Nervous System (ENS) plays a critical role in the propulsion of intestinal contents. This project expects to establish how specific functional classes of enteric neurons control propulsion along the gut. By recording the simultaneous neural activity from hundreds of different functional classes of enteric nerve cells simultaneously ....Cellular bases of enteric neural circuitry underlying gut propulsion. This project aims to investigate the neural bases of behaviour in the mammalian gut. The Enteric Nervous System (ENS) plays a critical role in the propulsion of intestinal contents. This project expects to establish how specific functional classes of enteric neurons control propulsion along the gut. By recording the simultaneous neural activity from hundreds of different functional classes of enteric nerve cells simultaneously, whilst recording intestinal muscle electrical activity and the movements of the gut wall, the project expects to identify which enteric neurochemical classes of neurons generate specific motor patterns along the intestine.Read moreRead less
Quantitative multi-modal optical imaging of deep tissue. This project aims to create new tools to quantify the structural and functional properties of tissue. Combining multiple optical imaging technologies (multi-modal) into a single, miniaturised probe, these tools could enable physiologists and biomedical researchers to obtain new insight into disease. Encasing the highly miniaturised probe within a medical needle is aimed to allow insertion of the 'needle probe' deep into tissue, extending o ....Quantitative multi-modal optical imaging of deep tissue. This project aims to create new tools to quantify the structural and functional properties of tissue. Combining multiple optical imaging technologies (multi-modal) into a single, miniaturised probe, these tools could enable physiologists and biomedical researchers to obtain new insight into disease. Encasing the highly miniaturised probe within a medical needle is aimed to allow insertion of the 'needle probe' deep into tissue, extending optical imaging to areas not previously accessible. The project could develop novel quantification models to allow longitudinal assessment and comparison between subjects. Validating the tools with specific biomarkers, it could provide outcomes in breast and liver cancer, and a framework to explore other diseases.Read moreRead less
The virtual human knee. This project aims to investigate the Virtual Human Knee (VHK) which provides a baseline knowledge about knee mechanics in healthy individuals and a tool for studying knee mechanics in silico. The new knowledge can be used for identifying individuals most at risk for injury, developing solutions for preventing injury and for assessing knee reconstruction and implantation methods. As such, VHK will mitigate the burden of knee injury to Australia and worldwide by progressing ....The virtual human knee. This project aims to investigate the Virtual Human Knee (VHK) which provides a baseline knowledge about knee mechanics in healthy individuals and a tool for studying knee mechanics in silico. The new knowledge can be used for identifying individuals most at risk for injury, developing solutions for preventing injury and for assessing knee reconstruction and implantation methods. As such, VHK will mitigate the burden of knee injury to Australia and worldwide by progressing disciplines including anatomy, bio-mechanics, sport science, rehabilitation, surgery and medical devices.Read moreRead less