Obesity increases the risk of developing diseases such as heart disease and type 2 diabetes, however not all obese people develop such diseases. Obese subjects with small fat cells are typically healthier than those with fewer, large fat cells. The applicants have identified a novel pathway that promotes the generation of new fat cells. This project will increase understanding of this pathway and may, ultimately, lead to new therapies that manipulate fat cell number and reduce obesity related di ....Obesity increases the risk of developing diseases such as heart disease and type 2 diabetes, however not all obese people develop such diseases. Obese subjects with small fat cells are typically healthier than those with fewer, large fat cells. The applicants have identified a novel pathway that promotes the generation of new fat cells. This project will increase understanding of this pathway and may, ultimately, lead to new therapies that manipulate fat cell number and reduce obesity related disease.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.
RhoA signaling: the nanoscale mechanisms of mechanochemical regulation. This project aims to elucidate a new paradigm for regulating cell signals at the nanoscale level. Cell signalling involves the coordination of multi-molecular networks at the plasma membrane, the interface between the cell and its external environment. These are often thought to involve the assembly of multimolecular complexes through the action of protein scaffolds. This project will focus on how the contractile regulator, ....RhoA signaling: the nanoscale mechanisms of mechanochemical regulation. This project aims to elucidate a new paradigm for regulating cell signals at the nanoscale level. Cell signalling involves the coordination of multi-molecular networks at the plasma membrane, the interface between the cell and its external environment. These are often thought to involve the assembly of multimolecular complexes through the action of protein scaffolds. This project will focus on how the contractile regulator, anillin, controls RhoA signalling by kinetic regulation. In particular, how nanoscale clustering of anillin by the dynamic actomyosin cytoskeleton modulates RhoA signalling for contractility and tissue homeostasis. The outcomes of this project are first and foremost fundamental understanding of how cells communicate with one another.Read moreRead less
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
Defining mechanisms behind the formation of hierarchical vascular networks. Blood vessels form complex branched networks composed of arteries, capillaries and veins. The development and maintenance of different vessel systems (arteries and veins) is dependent on cell adherence properties within each vessel, yet how these are established and maintained remains unknown. This project aims to analyse the differences in junctional dynamics between sprouting arteries and veins, and to identify arteria ....Defining mechanisms behind the formation of hierarchical vascular networks. Blood vessels form complex branched networks composed of arteries, capillaries and veins. The development and maintenance of different vessel systems (arteries and veins) is dependent on cell adherence properties within each vessel, yet how these are established and maintained remains unknown. This project aims to analyse the differences in junctional dynamics between sprouting arteries and veins, and to identify arterial and venous signalling networks that make and maintain vessel identity. This project will reveal how adhesiveness is regulated in order to make a hierarchical, functional vascular network, with implications for engineering of functional, vascularised organs in the biotech sector.Read moreRead less
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: DE210100604
Funder
Australian Research Council
Funding Amount
$436,600.00
Summary
How do cells sense and react to mechanical forces? There is accumulating evidence that mechanical forces exerted on tissues and cells strongly influences their behaviour. My research aims to understand how cells sense and respond to forces experienced throughout life. Using a combination of three-dimensional cell and tissue culture methods, I will investigate how compressive forces change the biochemistry of cells and their functionality. This work is aimed at generating fundamental knowledge to ....How do cells sense and react to mechanical forces? There is accumulating evidence that mechanical forces exerted on tissues and cells strongly influences their behaviour. My research aims to understand how cells sense and respond to forces experienced throughout life. Using a combination of three-dimensional cell and tissue culture methods, I will investigate how compressive forces change the biochemistry of cells and their functionality. This work is aimed at generating fundamental knowledge to improve our comprehension of how cells respond to force. The expected outcome is a greater understanding of mechanical and biochemical relationships between cells and the environment, to inform fields of tissue engineering of culture scaffolds to better mimic natural cell-tissue settings.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.
How filopodia connect macrophages to the outside world. Fundamental to life is the ability of cells to sense their surroundings and respond accordingly. This project aims to generate a biological understanding of how certain immune cells carry out such processes, thus enabling them to combat infections.