The role of actin in driving bulk endocytosis in neurons and neurosecretory cells. Synaptic release of neurotransmitter is essential for neuronal communication. Following fusion, synaptic vesicle membrane is incorporated into the plasma membrane and retrieved by endocytosis to recover both lipids and essential vesicular proteins. The project will characterise how the actin cytoskeleton perform this function.
The Role Of Intracellular Protein Trafficking In Alzheimer's Disease
Funder
National Health and Medical Research Council
Summary
Alzheimer’s disease (AD) is a progressive neurological disorder and is the most common cause of dementia. The development of therapies must be preceded by a thorough understanding of the molecular processes that underpin the disease. In this project we will examine the interactions between the Alzheimer’s precursor protein (APP) and the molecular machinery that controls its intracellular localization and breakdown to the toxic A? peptide that is central to disease pathology.
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE120100037
Funder
Australian Research Council
Funding Amount
$350,000.00
Summary
A cellular nano-imaging facility: Probing cellular complexity. Answering the major medical and biotechnology questions of the 21st century will be heavily reliant on the use of advanced imaging techniques. This facility will establish a new and revolutionary microscope which is capable of producing images of living cells in action at high magnification and with the greatest clarity.
Deciphering the cellular defences against aggregating proteins in human disease. Cells have inbuilt defences for coping with proteins that bend into abnormal sticky shapes that form toxic clusters. In many diseases, including Huntington's, the clusters severely damage nerve cells. This project will identify the genes and mechanisms cells use to protect themselves from toxic clusters, which could provide new therapeutic targets.
The endosome at atomic resolution. The project seeks to improve understanding of intracellular transport. The transport of proteins is essential for controlling the interactions of a cell with its environment, and for regulating a huge number of cell signalling events. The retromer protein complex is a central mediator of intracellular trafficking in organelles called endosomes. It is vital for normal cell homeostasis in all eukaryotic organisms, and is an emerging target for treatment of human ....The endosome at atomic resolution. The project seeks to improve understanding of intracellular transport. The transport of proteins is essential for controlling the interactions of a cell with its environment, and for regulating a huge number of cell signalling events. The retromer protein complex is a central mediator of intracellular trafficking in organelles called endosomes. It is vital for normal cell homeostasis in all eukaryotic organisms, and is an emerging target for treatment of human neurodegenerative diseases. This project plans to use a combination of cutting-edge X-ray crystallographic and electron microscopy approaches to develop a multi-scale, pseudo-atomic structure of retromer and key regulatory proteins to understand how this multi-component protein machinery is assembled to control intracellular transport.Read moreRead less
Defining systems that clear dangerous misfolded proteins from body fluids. The project intends to establish how the human body defends itself against protein-folding related disease and loss of quality of life. Exposure to everyday physical and chemical stresses can cause proteins to lose their normal shape and become misfolded. Misfolded proteins are causally involved in human ageing and serious diseases (for example, Alzheimer's disease). However, the body does have a protective system that cl ....Defining systems that clear dangerous misfolded proteins from body fluids. The project intends to establish how the human body defends itself against protein-folding related disease and loss of quality of life. Exposure to everyday physical and chemical stresses can cause proteins to lose their normal shape and become misfolded. Misfolded proteins are causally involved in human ageing and serious diseases (for example, Alzheimer's disease). However, the body does have a protective system that clears dangerous misfolded proteins from body fluids. Using cutting-edge approaches and a novel animal model, the project aims to establish how this system works. The outcomes are expected to improve understanding of the molecular processes affecting human ageing and disease and strengthen the framework needed to develop better strategies to combat these.Read moreRead less
Defining the molecular mechanisms of intracellular protein trafficking. Intracellular trafficking of proteins is critical for normal cell function and defects can lead to many different human diseases. Outcomes from this project will lead to insights into how trafficking is regulated at the atomic level and will help place Australia at the forefront of international efforts to understand this essential process.
A role for the actin cytoskeleton in suppression of prion pathology in yeast. The discovery that proteins as well as DNA carry genetic information is leading to a re-think of the mechanisms that program cell behaviour. There is a link between proteins that suppress cancer and protein inheritance. This project explores how heritable changes in proteins control cell behaviour and the implications of this for the origin of cancer.
Investigating the intercellular trafficking of proteins and RNA and its relevance to neurodegenerative diseases. Alzheimer's and prion diseases are neurodegenerative disorders associated with protein misfolding. This project brings together similar features of these diseases using novel cell- and animal-based studies to develop a greater understanding of the molecular basis of these disorders.