Modulating Inflammatory And Fibrogenic Pathways In Kidney Disease Using A Novel Antagonist Of Protease-Activated-Receptor-2
Funder
National Health and Medical Research Council
Funding Amount
$581,116.00
Summary
Chronic kidney disease (CKD) now affects 10% of adults in industrialised countries. Current treatments are largely ineffective. Thus developing better CKD treatments will have substantial public health benefit. Three well established and clinically relevant animal models of kidney disease will be used to test the ability of a new experimental anti-inflammatory drug, developed by members of this research team at The University of Queensland, to prevent or lessen the progression of CKD.
Investigation of novel mechanisms for the regulation of sperm-oocyte interactions. Through work with national and international collaborators, this project aims to provide unprecedented insights into how spermatozoa recognise and bind to an oocyte. The approach is based on strong preliminary data indicating that molecular chaperones play a key role in the functional remodelling of the spermatozoon by promoting the assembly of multimeric oocyte receptor complexes. Through the use of state-of-the ....Investigation of novel mechanisms for the regulation of sperm-oocyte interactions. Through work with national and international collaborators, this project aims to provide unprecedented insights into how spermatozoa recognise and bind to an oocyte. The approach is based on strong preliminary data indicating that molecular chaperones play a key role in the functional remodelling of the spermatozoon by promoting the assembly of multimeric oocyte receptor complexes. Through the use of state-of-the-art cell biology and proteomic technologies, the project aims to investigate how molecular chaperones orchestrate these changes and in doing so, improve understanding of the fertilisation cascade and open up new contraceptive strategies.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
Discovery Early Career Researcher Award - Grant ID: DE120102914
Funder
Australian Research Council
Funding Amount
$375,000.00
Summary
Membrane protein function in its native lipid environment characterised by solid-state nuclear magnetic resonance. Membrane proteins play an important role for cell function and have vast medical implications, whereas their function is crucially dependent on mechanisms related to their embedding in the membrane. These features will be characterised by newly developed spectroscopic methods, which will further contribute to an improved understanding of diseases.
Discovery Early Career Researcher Award - Grant ID: DE170100167
Funder
Australian Research Council
Funding Amount
$372,000.00
Summary
Molecular signals guiding dynamic cell movement during blood vessel growth. This project aims to discover how cells interact within the developing blood vessel sprout. Blood vessels form complex branched networks composed of arteries, capillaries and veins that supply oxygen and nutrients to all body tissues. The development and maintenance of blood vessels depends on the coordination of movement and adhesion between individual endothelial cells in the vessel wall, but the signals controlling th ....Molecular signals guiding dynamic cell movement during blood vessel growth. This project aims to discover how cells interact within the developing blood vessel sprout. Blood vessels form complex branched networks composed of arteries, capillaries and veins that supply oxygen and nutrients to all body tissues. The development and maintenance of blood vessels depends on the coordination of movement and adhesion between individual endothelial cells in the vessel wall, but the signals controlling these actions are unknown. This project aims to reveal how the vascular tree forms during development, which is expected to improve the engineering of functional, vascularised organs in the biotech sector.Read moreRead less
Tuning Molecular Translocaton by Close-Field Electroporation. This project aims to determine the underlying mechanisms by which DNA and other molecules are able to migrate across the cell membrane in response to highly localised electric fields. It has recently been shown that focusing of electric fields at the cellular level, using an array of small electrodes, results in unexpectedly high cell transfection efficiencies. It has been termed 'close-field electroporation'. Here it is proposed t ....Tuning Molecular Translocaton by Close-Field Electroporation. This project aims to determine the underlying mechanisms by which DNA and other molecules are able to migrate across the cell membrane in response to highly localised electric fields. It has recently been shown that focusing of electric fields at the cellular level, using an array of small electrodes, results in unexpectedly high cell transfection efficiencies. It has been termed 'close-field electroporation'. Here it is proposed to establish the properties of the electric fields around cells and cell membrane interactions with these fields that enable molecular translocation. This fundamental science could have broad implications in the domains of drug delivery, gene therapy and neural stimulation.Read moreRead less