How do protein quality control mechanisms maintain neuronal ageing? This project aims to interrogate how mechanisms of protein quality control act in the brain - an organ that is particularly vulnerable to a high load of misfolded protein - to maintain normal physiology during ageing. This project expects to make advances in cellular biochemistry and neuroscience, using an innovative proximity labelling approach to identify quality control regulators in neurons that specifically engage with misf ....How do protein quality control mechanisms maintain neuronal ageing? This project aims to interrogate how mechanisms of protein quality control act in the brain - an organ that is particularly vulnerable to a high load of misfolded protein - to maintain normal physiology during ageing. This project expects to make advances in cellular biochemistry and neuroscience, using an innovative proximity labelling approach to identify quality control regulators in neurons that specifically engage with misfolded proteins during ageing, within the nervous system of a living animal. Expected outcomes of this project will generate new knowledge of brain physiology and ageing relevant to all animals. This should provide significant benefits, such as a greater understanding of long-term brain functions including memory.Read moreRead less
Development of a gene delivery system to access neuronal cells. Understanding the pathways for gene delivery and efficient expression will result in new knowledge in the areas of biotechnology and cell biology. This project will result in significant new information on vesicular trafficking pathways in neurons. An effective gene delivery system will realise significant commercial potential for our partner organisations and economic benefit to other Australian industry. This project aligns direct ....Development of a gene delivery system to access neuronal cells. Understanding the pathways for gene delivery and efficient expression will result in new knowledge in the areas of biotechnology and cell biology. This project will result in significant new information on vesicular trafficking pathways in neurons. An effective gene delivery system will realise significant commercial potential for our partner organisations and economic benefit to other Australian industry. This project aligns directly with the National Research Priority of "Promoting and maintaining good health" with a specific benefit for patients that suffer mental and physical degeneration and for their families.Read moreRead less
Defining the spatial and temporal regulation of neurite branching. This project aims to identify mechanisms via which the cytoskeleton regulates the branching of nerve cell extensions. The formation of branched cell extensions is essential for establishing a complex network of connecting and communicating nerve cells in all higher organisms. This project expects that by combining advanced light microscopy technology and recently developed tools for the study of the cell architecture in vitro and ....Defining the spatial and temporal regulation of neurite branching. This project aims to identify mechanisms via which the cytoskeleton regulates the branching of nerve cell extensions. The formation of branched cell extensions is essential for establishing a complex network of connecting and communicating nerve cells in all higher organisms. This project expects that by combining advanced light microscopy technology and recently developed tools for the study of the cell architecture in vitro and in vivo, we will be able to define the molecular changes in neurites that control neurite branching. This should provide significant benefits, such as gaining crucial insights into the mechanisms of forming complex neuronal networks.Read moreRead less
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
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE120100027
Funder
Australian Research Council
Funding Amount
$320,000.00
Summary
Sensitive and multinuclear: a dedicated facility for high-throughput characterisation of small molecules. This project will provide new cutting edge nuclear magnetic resonance equipment will enhance an existing shared analysis facility based at University of New South Wales. The new equipment will underpin research in polymers, neuropharmacology, the biological basis of inherited disease, nanomedicine, bioactive compounds and toxins.
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