Discovery Early Career Researcher Award - Grant ID: DE180100206
Funder
Australian Research Council
Funding Amount
$365,058.00
Summary
Intelligently linking nanoscience to neuroscience with glycan biology. This project aims to provide a comprehensive description of the unique cell-surface glycan expression on inflamed neurons, astrocytes, microglia and oligodendrocytes. This project will use glycan profiling data to engineer luminescent nanoparticles with superior neuroimaging qualities for cell type-specific in vivo targeting and drug delivery in the central nervous system. The project outcomes are expected to improve our fund ....Intelligently linking nanoscience to neuroscience with glycan biology. This project aims to provide a comprehensive description of the unique cell-surface glycan expression on inflamed neurons, astrocytes, microglia and oligodendrocytes. This project will use glycan profiling data to engineer luminescent nanoparticles with superior neuroimaging qualities for cell type-specific in vivo targeting and drug delivery in the central nervous system. The project outcomes are expected to improve our fundamental understanding of neurobiological cell-surfaces.Read moreRead less
Targeting brain lipid homeostasis to treat Alzheimer's disease. Dementia affects approximately 250,000 people in Australia at an estimated cost (in 2002) of $6.6 billion per annum. The major cause of dementia (accounting for approximately 70% of all cases) is Alzheimer's disease (AD); a progressive neurodegenerative illness for which there is no curative or disease-stalling treatment. Due to increases in life expectancy, the incidence of AD is predicted to triple by 2050 unless disease-modifying ....Targeting brain lipid homeostasis to treat Alzheimer's disease. Dementia affects approximately 250,000 people in Australia at an estimated cost (in 2002) of $6.6 billion per annum. The major cause of dementia (accounting for approximately 70% of all cases) is Alzheimer's disease (AD); a progressive neurodegenerative illness for which there is no curative or disease-stalling treatment. Due to increases in life expectancy, the incidence of AD is predicted to triple by 2050 unless disease-modifying treatments are developed. This research program will provide novel realistic pharmaceutical approaches to treat AD. Even if the onset of AD could be delayed by a few years the personal and financial benefits would be enormous. The potential for this research to generate commercially viable Australian intellectual property is also significant.Read moreRead less
Biomagnification of the biotoxin BMAA in the environment. Using unique models and technics, the project aims to demonstrate that long-term exposure to the blue green algae toxin β-N-methylamino-l-alanine (BMAA) leads to uptake, accumulation and toxicity within the central nervous system. The risks for heath, mechanisms of contamination and toxicity of BMAA are very poorly understood. Algal blooms cost the Australian community more than $250 million each year and represent a major health issue fo ....Biomagnification of the biotoxin BMAA in the environment. Using unique models and technics, the project aims to demonstrate that long-term exposure to the blue green algae toxin β-N-methylamino-l-alanine (BMAA) leads to uptake, accumulation and toxicity within the central nervous system. The risks for heath, mechanisms of contamination and toxicity of BMAA are very poorly understood. Algal blooms cost the Australian community more than $250 million each year and represent a major health issue for human and fauna. This project aims to be the first to fully characterise BMAA mechanisms of contamination and neurotoxicity and to highlight the major environmental risk of exposure of human to BMAA. It also aims to develop new and unique detection and quantification tools for BMAA.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE0453295
Funder
Australian Research Council
Funding Amount
$369,697.00
Summary
NMR cryosystem for structural and functional biology. State-of-the-art hardware is requested for the 600-MHz NMR spectrometers situated at University of Sydney and UNSW. A cryosystem installed at USyd. will provide a massive boost in productivity and will allow projects previously inaccessible due to excessive turn-around times, or sensitivity or solubility problems to become tractable. This system will provide new opportunities to researchers from USyd., UNSW and ANU, but will restrict the ver ....NMR cryosystem for structural and functional biology. State-of-the-art hardware is requested for the 600-MHz NMR spectrometers situated at University of Sydney and UNSW. A cryosystem installed at USyd. will provide a massive boost in productivity and will allow projects previously inaccessible due to excessive turn-around times, or sensitivity or solubility problems to become tractable. This system will provide new opportunities to researchers from USyd., UNSW and ANU, but will restrict the versatility of the USyd. instrument. The installation of a TBI probe at UNSW will counter this, and provide a REAL network of NMR instruments across NSW and the ACT.Read moreRead less
The role of tropomyosin in coordinated neurite branching. This project will explore how nerve cells generate a highly branched network of cell processes which allows all higher functions of the nervous system. We previously discovered the central role of a component of the cell architecture in determining the branching pattern and in this project expect to reveal the molecular basis for its function.
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
The mode of action of the haem protein neuroglobin in protecting nerve cells. Outcomes from this project will assist in developing new treatments for stroke and chronic degenerative brain disorders by characterising how the haem protein neuroglobin protects neurons of the central and peripheral nervous system from oxidative damage. This project will also develop pharmacological strategies to boost the concentration of neuroglobin in neurons.
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
Single cell imaging of trace elements by laser ablation - inductively coupled plasma - mass spectrometry. The precise mechanism of how many diseases function on the cellular level is not well understood. Trace elements are important to normal cellular function and have the potential to cause significant damage if delicate levels are disturbed. This project will introduce a new, cost-effective alternative to the synchrotron for mapping of trace elements in single cells. This breakthrough science ....Single cell imaging of trace elements by laser ablation - inductively coupled plasma - mass spectrometry. The precise mechanism of how many diseases function on the cellular level is not well understood. Trace elements are important to normal cellular function and have the potential to cause significant damage if delicate levels are disturbed. This project will introduce a new, cost-effective alternative to the synchrotron for mapping of trace elements in single cells. This breakthrough science will transform a common analytical instrument into a powerful new tool for probing the cellular mechanisms of chronic illness. This frontier technology will help determine the role of trace metals in the development of neurodegenerative disease.Read moreRead less
The role of copper in the early ubiquitination pathway. This project aims to explore the role of copper in ageing and protein turnover. The removal of damaged or excess proteins is achieved by ubiquitin-tagging in all kingdoms of life. It has recently been observed that one of the earliest steps of this process appears to be driven by copper. This project aims to elaborate the precise biochemical mechanisms by which copper regulates this important tagging and protein turnover system. It proposes ....The role of copper in the early ubiquitination pathway. This project aims to explore the role of copper in ageing and protein turnover. The removal of damaged or excess proteins is achieved by ubiquitin-tagging in all kingdoms of life. It has recently been observed that one of the earliest steps of this process appears to be driven by copper. This project aims to elaborate the precise biochemical mechanisms by which copper regulates this important tagging and protein turnover system. It proposes to characterise the structure and function of a newly identified copper-dependent form of cell enzyme which could be involved in amplifying ubiquitin-tagged protein breakdown. Copper is essential for life in all domains. Identifying copper as a major regulator in protein clearance is important in understanding this fundamental biological machinery.Read moreRead less