How Do Mutations In Autophagy Receptors Cause FTD And ALS?
Funder
National Health and Medical Research Council
Funding Amount
$566,966.00
Summary
As cells age the "garbage disposal" process within cells slows down, becoming less functional. In inherited forms of dementia the genes involved often code for damaged proteins that "clog up" the disposal system or directly affect the “garbage men”. These defective garbage men genes include SQSTM1/p62, OPTN, VCP and UBQLN2. We will determine how these defective genes lead to build up of garbage in neuronal cells and how leads to disease.
How cell shape regulators control cell competition in tissue development. This project aims to determine how cell shape (polarity) regulators affect cell survival in an epithelial tissue. When mutation or wounding perturb cell shape regulators in a tissue cell, signalling pathways are altered that kill the aberrant cells. A surveillance mechanism termed "cell competition" is important to remove the damaged cells. This project will investigate a potential regulator of cell competition, the tyrosi ....How cell shape regulators control cell competition in tissue development. This project aims to determine how cell shape (polarity) regulators affect cell survival in an epithelial tissue. When mutation or wounding perturb cell shape regulators in a tissue cell, signalling pathways are altered that kill the aberrant cells. A surveillance mechanism termed "cell competition" is important to remove the damaged cells. This project will investigate a potential regulator of cell competition, the tyrosine phosphatase PTP61F, in response to perturbation of cell shape regulators, using the vinegar fly, Drosophila, and mammalian systems. This study is expected to reveal biomarkers that can be used to improve organismal fitness to increase productivity or to decrease it for pest control.Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE170100239
Funder
Australian Research Council
Funding Amount
$372,000.00
Summary
The molecular basis of endothelial mechanotransduction through TRPV4. This project aims to understand how blood flow dynamics coordinate the plasma membrane localisation and interaction of the transient receptor potential vanilloid 4 (TRPV4), a candidate mechanosensitive ion channel broadly expressed in endothelium with physiological and pathological roles in the cardiovascular system, with other mechanoreceptors and the physiological relevance of these events. Blood flow haemodynamics affect ca ....The molecular basis of endothelial mechanotransduction through TRPV4. This project aims to understand how blood flow dynamics coordinate the plasma membrane localisation and interaction of the transient receptor potential vanilloid 4 (TRPV4), a candidate mechanosensitive ion channel broadly expressed in endothelium with physiological and pathological roles in the cardiovascular system, with other mechanoreceptors and the physiological relevance of these events. Blood flow haemodynamics affect cardiovascular health and morphogenesis. This project will highlight the role of TRPV4 channels in the short- and long-term adaptive responses to shear stress and will also have significant potential for application in future drug discovery.Read moreRead less
Nano-scale organisation of cellular adhesions. Cell migration is a key aspect of many normal processes but also of diseases such as cancers. This project will use a novel fluorescence microscope that can see single proteins to identify how cell adhesions are formed, remodelled and disassembled. This knowledge will help to design better drugs against cancers and novel implantable materials.
Discovery Early Career Researcher Award - Grant ID: DE140100558
Funder
Australian Research Council
Funding Amount
$389,220.00
Summary
Caveolae as structural mechanosensors: a link between the intra and extracellular environments? How cells perceive and respond to mechanical cues are fundamental questions in cellular biology. Caveolae are invaginations of the plasma membrane which flatten into the bulk membrane in response to increased membrane tension. This project aims to validate this response at the molecular level in a physiological context. Specifically, the project will investigate how the caveola response coordinates wi ....Caveolae as structural mechanosensors: a link between the intra and extracellular environments? How cells perceive and respond to mechanical cues are fundamental questions in cellular biology. Caveolae are invaginations of the plasma membrane which flatten into the bulk membrane in response to increased membrane tension. This project aims to validate this response at the molecular level in a physiological context. Specifically, the project will investigate how the caveola response coordinates with the extracellular matrix as well as study the fate of caveolar proteins released from caveolae. Besides the establishment of new methodologies, the findings will highlight the role of caveolae in the short and long term adaptive responses to mechanical cues and enhance understanding of how cells integrate the extracellular and intracellular environments.Read moreRead less
The Characterization Of A Novel Pseudokinase Regulator Of Platelet Formation
Funder
National Health and Medical Research Council
Funding Amount
$372,965.00
Summary
Mammalian cells contain a complex switchboard, which directs the cell to grow, die, multiply or move in response to external cues. When communication breaks down within the cell, diseases arise. Our studies are directed towards identifying the molecules that comprise the switchboard which directs blood cell formation. A detailed understanding of the regulators of blood cell formation will equip us with a sound starting point for designing drugs to ameliorate blood diseases.
Novel models to advance our understanding of mammalian development. This project aims to add to the understanding of cellular processes underpinning mammalian development. Protein phosphorylation is a dynamic process regulated by both protein kinases and protein phosphatases. While the role of kinases in cellular functions are well defined, the roles of protein phosphatases are not well understood. Using a range of laboratory models this project aims to discover the function of the phosphatase P ....Novel models to advance our understanding of mammalian development. This project aims to add to the understanding of cellular processes underpinning mammalian development. Protein phosphorylation is a dynamic process regulated by both protein kinases and protein phosphatases. While the role of kinases in cellular functions are well defined, the roles of protein phosphatases are not well understood. Using a range of laboratory models this project aims to discover the function of the phosphatase PP2A, in cell proliferation, survival, differentiation and DNA damage repair. The anticipated outcome is an improved understanding of all stages of mammalian development. This will provide significant benefits in the biotechnology, chemical and pharmaceutical industries.Read moreRead less
Dynamic regulation of cell signalling scaffolds. This project aims to determine how cells utilise scaffold-type signalling proteins to orchestrate, over time, diverse cellular responses critical for normal development and physiology. The project expects to generate fundamental new knowledge in cell and synthetic biology with broad relevance that will foster establishment of new international linkages and networks. This research should benefit the biotechnology sector by identifying strategies fo ....Dynamic regulation of cell signalling scaffolds. This project aims to determine how cells utilise scaffold-type signalling proteins to orchestrate, over time, diverse cellular responses critical for normal development and physiology. The project expects to generate fundamental new knowledge in cell and synthetic biology with broad relevance that will foster establishment of new international linkages and networks. This research should benefit the biotechnology sector by identifying strategies for engineering scaffolds with desired biological outputs, with applications in areas such as large-scale cell production, immunotherapy, wound healing and regenerative medicine.Read moreRead less
Mechanotransduction: a new paradigm for cadherin junction biology. Cell adhesion is necessary to hold the cells in our tissue together, and is essential for organ function. It is essential for adhesion junctions to resist force that would break them apart. This project investigates how adhesion junctions sense and respond to force acting on cells.
The discovery and characterisation of novel protein regulators of blood cell formation. All of the mature blood cells in the human body are derived from a common ancestor cell type known as a stem cell. Our proposed studies will enhance our knowledge of how functional, mature blood cells are formed from stem cells and how dysregulation of these normally tightly controlled pathways can give rise to severe blood diseases.