Single minded 1 in neuron development and satiety signalling. An understanding of how Single minded 1 (SIM1) regulates target genes may allow new pharmaceutical approaches to be designed to combat obesity. As Sim1 belongs to a family of closely related gene regulatory proteins which function in early development and homeostasis, deciphering the molecular control mechanisms of Sim1 may help understand how the related factors function in processes such as angiogenesis, response to low oxygen stres ....Single minded 1 in neuron development and satiety signalling. An understanding of how Single minded 1 (SIM1) regulates target genes may allow new pharmaceutical approaches to be designed to combat obesity. As Sim1 belongs to a family of closely related gene regulatory proteins which function in early development and homeostasis, deciphering the molecular control mechanisms of Sim1 may help understand how the related factors function in processes such as angiogenesis, response to low oxygen stress, invasion of environmental pollutants and autism spectrum diseases. The ability to manipulate these factors would be of great benefit in treating a range of disorders, but a thorough molecular understanding of these factors needs be obtained prior to attempting design of pharmaceuticals.Read moreRead less
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
Truncating presenilin mutations and their effects on gamma-secretase activity, tau and beta-catenin - insights into Alzheimers disease and cancer. Cancer and dementia are primarily afflictions of the aged and are increasingly important in an aging Australian population. 95% of all Alzheimer's disease is spontaneous (not inherited) but we know little about the molecular mechanisms underlying it. Our discovery that truncated presenilin proteins potently inhibit normal protein function suggests tha ....Truncating presenilin mutations and their effects on gamma-secretase activity, tau and beta-catenin - insights into Alzheimers disease and cancer. Cancer and dementia are primarily afflictions of the aged and are increasingly important in an aging Australian population. 95% of all Alzheimer's disease is spontaneous (not inherited) but we know little about the molecular mechanisms underlying it. Our discovery that truncated presenilin proteins potently inhibit normal protein function suggests that changes in presenilin function in aged cells might be a common molecular link between spontaneous and inherited Alzheimer's disease and could contribute to frontotemporal dementia and cancer. Our research will show whether this phenomenon might provide a breakthrough in our understanding of these diseases and be a productive area for research into their amelioration and/or prevention.Read moreRead less
Novel mechanisms integrating the central and autonomic nervous system. This project aims to define molecular mechanisms controlling the exquisite connectivity of neurons in different parts of the body. The ability of higher-vertebrates to respond to different environmental conditions is essential for life, evolution, health, reproduction and growth, and is reliant on the autonomic nervous system. However, how the autonomic nervous system is integrated with the central nervous system to control h ....Novel mechanisms integrating the central and autonomic nervous system. This project aims to define molecular mechanisms controlling the exquisite connectivity of neurons in different parts of the body. The ability of higher-vertebrates to respond to different environmental conditions is essential for life, evolution, health, reproduction and growth, and is reliant on the autonomic nervous system. However, how the autonomic nervous system is integrated with the central nervous system to control holistic physiological responses is largely unknown. By deciphering how neural networks are formed this project aims to provide broad biological insight to wiring of the entire nervous system which is likely to have significant implications for the formation of synthetic neural networks and for regeneration.Read moreRead less
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
Understanding the molecular mechanisms of intellectual disability. Intellectual disability is frequent in the population, with one in every fifty people in the world directly affected. This project will improve our understanding of the correct development and function of the brain required for cognition by investigating specific roles and regulation of key molecules involved.
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.