Discovery Early Career Researcher Award - Grant ID: DE130100117
Funder
Australian Research Council
Funding Amount
$375,000.00
Summary
Allosteric fingerprinting of G protein-coupled receptor monomers and oligomers. Allosteric modulation describes interactions between distinct, but conformationally linked, binding sites. Research will develop enabling technology using the unique profile, or 'fingerprint', of allosteric modulation at interacting and non-interacting G protein-coupled receptors to probe for receptor complexes within healthy and diseased tissue.
Novel regulation of TRP channels by oxygen-dependent hydroxylation. Factor inhibiting HIF-1 (FIH-1) is an oxygen-sensing asparaginyl hydroxylase. A bioinformatic search identified specific transient receptor potential (TRP) ion channels as likely substrates. The hypothesis is that TRP channels are regulated by hypoxia, mediated through a novel mechanism of oxygen-dependent hydroxylation by FIH. The aim of this project is to investigate how hydroxylation by FIH mediates the hypoxic regulation of ....Novel regulation of TRP channels by oxygen-dependent hydroxylation. Factor inhibiting HIF-1 (FIH-1) is an oxygen-sensing asparaginyl hydroxylase. A bioinformatic search identified specific transient receptor potential (TRP) ion channels as likely substrates. The hypothesis is that TRP channels are regulated by hypoxia, mediated through a novel mechanism of oxygen-dependent hydroxylation by FIH. The aim of this project is to investigate how hydroxylation by FIH mediates the hypoxic regulation of TRP channels. Preliminary data show that the first candidate, TRPV3, is activated in hypoxia, is hydroxylated by FIH, and hydroxylation mediates changes in activity. Ion channels are important for the physiological response to hypoxia, and this project aims to define a novel mechanism for this response, with relevance to mammalian physiology.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.
Transcriptional control of neural stem cell differentiation during development and disease. Understanding the molecular mechanisms that control how neural stem cells differentiate is critical to provide potential therapeutic treatment for neurodegenerative diseases and for brain cancer. This project will aim to discover, using an animal model system, the genes and molecules regulating these key biological processes.
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE120100091
Funder
Australian Research Council
Funding Amount
$250,000.00
Summary
A five laser multichannel flow cytometry cell sorter for the University of New South Wales as part of an advanced flow cytometry network. Flow cytometry is a technique for counting and examining microscopic particles, such as cells and chromosomes, by suspending them in a stream of fluid and passing them by an electronic detection apparatus. This project will establish such advanced cell sorting instrumentation at the University of New South Wales, providing this capability to a wide range of re ....A five laser multichannel flow cytometry cell sorter for the University of New South Wales as part of an advanced flow cytometry network. Flow cytometry is a technique for counting and examining microscopic particles, such as cells and chromosomes, by suspending them in a stream of fluid and passing them by an electronic detection apparatus. This project will establish such advanced cell sorting instrumentation at the University of New South Wales, providing this capability to a wide range of researchers in diverse fields. The project will also provide a basis for establishing a flow cytometry network with partner institutes University of Sydney and the University of Technology, Sydney.Read moreRead less
How the brain regulates blood pressure. This project will test whether a group of nerve cells in the rostral ventrolateral medulla generate sympathetic activity in blood vessels. The brain regulates blood pressure through several pathways, including nerves in the sympathetic nervous system that constrict blood vessels and increase the heart rate. Activity of these sympathetic nerves regulates blood pressure, but it is unknown which nerve cells in the brain cause this activity. This information i ....How the brain regulates blood pressure. This project will test whether a group of nerve cells in the rostral ventrolateral medulla generate sympathetic activity in blood vessels. The brain regulates blood pressure through several pathways, including nerves in the sympathetic nervous system that constrict blood vessels and increase the heart rate. Activity of these sympathetic nerves regulates blood pressure, but it is unknown which nerve cells in the brain cause this activity. This information is essential to understand how blood pressure is controlled under healthy conditions.Read moreRead less
Psychiatric disorders in epilepsy. Psychiatric disorders, such as depression, anxiety and cognitive disorders, are frequently observed in patients with epilepsy. Although standard dogma suggests that psychiatric disorders are a consequence of living with epilepsy, recent evidence suggests a bidirectional relationship between these disorders, such that depression and other psychiatric illnesses act as risk factors for epilepsy development. This project will utilise basic science approaches to und ....Psychiatric disorders in epilepsy. Psychiatric disorders, such as depression, anxiety and cognitive disorders, are frequently observed in patients with epilepsy. Although standard dogma suggests that psychiatric disorders are a consequence of living with epilepsy, recent evidence suggests a bidirectional relationship between these disorders, such that depression and other psychiatric illnesses act as risk factors for epilepsy development. This project will utilise basic science approaches to understand the causal relationships between epilepsy and psychiatric disorders, and determine how and why psychiatric disorders and epilepsy co-exist. It is hoped that research conducted in this project will develop novel avenues to treatment of both epilepsy and psychiatric disorders.Read moreRead less
UNDERSTANDING THE BASIS OF COMPLEX BEHAVIOUR. This project is anchored in the fundamental understanding of complex vertebrate behaviours, namely cognition. Little is known about the molecular and neural substrates underpinning complex higher order information processing. This project aims to dissect the functional role of synaptic genes that are essential for organising neuronal connections, in distinct cognitive processes and how these functions may be regulated by other genes, drugs or environ ....UNDERSTANDING THE BASIS OF COMPLEX BEHAVIOUR. This project is anchored in the fundamental understanding of complex vertebrate behaviours, namely cognition. Little is known about the molecular and neural substrates underpinning complex higher order information processing. This project aims to dissect the functional role of synaptic genes that are essential for organising neuronal connections, in distinct cognitive processes and how these functions may be regulated by other genes, drugs or environmental factors. This project aims to employ state-of-the-art technologies to address the evolutionary biology of complex cognitive behaviours, towards further understandings how brain function evolved and the mechanisms that have enabled humans to perform highly complex and intricate tasks.Read moreRead less
Development of novel reagents that specifically counteract EphA4 to enhance axonal regeneration. This project will examine the role of EphA4, an important guidance protein, in neural cell regeneration. The goal is to understand the signalling mechanisms that inhibit regeneration in the central nervous system and to develop novel biological agents to overcome these processes and promote functional recovery after nervous system injury or disease.
Understanding the generation of hypothalamic sleep neurons. This Project aims to investigate the mechanisms controlling the formation of the sleep neurons in the hypothalamus. We all sleep, and normal sleep-wake cycles play a central role in our biology. The functional role of these sleep neurons in the mature brain are well established. However, how the neurons are generated during development is very poorly defined. This project aims to address this critical knowledge gap, and will greatly inc ....Understanding the generation of hypothalamic sleep neurons. This Project aims to investigate the mechanisms controlling the formation of the sleep neurons in the hypothalamus. We all sleep, and normal sleep-wake cycles play a central role in our biology. The functional role of these sleep neurons in the mature brain are well established. However, how the neurons are generated during development is very poorly defined. This project aims to address this critical knowledge gap, and will greatly increase our understanding of how the development of this critical aspect of organismal function is orchestrated during development. This project will also develop bioinformatics tools with broad utility within the biosciences field and enhance the capacity for interdisciplinary international collaborations.Read moreRead less