A Fibroin-based Prosthetic Bruch's Membrane For The Treatment Of Age-related Macular Degeneration
Funder
National Health and Medical Research Council
Funding Amount
$538,080.00
Summary
Our aim is to develop a new therapy for the treatment of patients with age-related macular degeneration (AMD), a leading cause of blindness in our ageing population. The novelty of our therapy resides in using a protein derived from silk fibers (fibroin), to rebuild a healthy barrier between the outermost layer of the retina and adjacent blood vessels. We expect that the findings from this study will eventually lead to better outcomes for patients with AMD.
Control of actin assembly by cell-cell adhesion: molecular effectors and higher order function. Functional cooperation between the actin cytoskeleton and cadherin cell-cell adhesion molecules plays critical roles during development and morphogenesis. This proposal builds on my lab's recent discovery that E-cadherin interacts with and regulates the Arp2/3 actin nucleator complex, a central determinant of actin assembly in cells. We will explore key implications of this finding, concentrating on d ....Control of actin assembly by cell-cell adhesion: molecular effectors and higher order function. Functional cooperation between the actin cytoskeleton and cadherin cell-cell adhesion molecules plays critical roles during development and morphogenesis. This proposal builds on my lab's recent discovery that E-cadherin interacts with and regulates the Arp2/3 actin nucleator complex, a central determinant of actin assembly in cells. We will explore key implications of this finding, concentrating on defining the molecular mechanisms that regulate Arp2/3 and actin assembly in cadherin-based adhesion. Our work combines molecular characterization of regulatory mechanisms and proteomic searches for new regulators, with tests of the higher-order function of this novel process in cell adhesion and recognition.Read moreRead less
Balancing cadherin-actin cooperation: the key regulatory role of Ena/VASP proteins. This project analyses a fundamental mechanism of how cells work together in tissues. Understanding the fundamental mechanisms of how cells work will provide important basic scientific information to enrich the scientific expertise in Australia and its part in the international community, generate insights relevant for understanding human disease and physical degeneration, and support the training of young scienti ....Balancing cadherin-actin cooperation: the key regulatory role of Ena/VASP proteins. This project analyses a fundamental mechanism of how cells work together in tissues. Understanding the fundamental mechanisms of how cells work will provide important basic scientific information to enrich the scientific expertise in Australia and its part in the international community, generate insights relevant for understanding human disease and physical degeneration, and support the training of young scientists in Australia.Read moreRead less
Tissue tension homeostasis by junctional mechanosensing. This project examines how tissues use mechanical tension to preserve their integrity. This comes from the recent appreciation that cells pull on the connections between each other to generate tension. Further, molecular mechanisms exist for cells to sense changes in this tension and then to enlist the appropriate responses to restore tension. The project aims to test how local changes in tension are detected and corrected, when tissue inte ....Tissue tension homeostasis by junctional mechanosensing. This project examines how tissues use mechanical tension to preserve their integrity. This comes from the recent appreciation that cells pull on the connections between each other to generate tension. Further, molecular mechanisms exist for cells to sense changes in this tension and then to enlist the appropriate responses to restore tension. The project aims to test how local changes in tension are detected and corrected, when tissue integrity is compromised by very different causes. The project endeavours to establish a new conceptual paradigm for understanding tissue homeostasis, based on cell biology and biomechanics, with implications for developmental biology and tissue engineering.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
Red Cell Polymorphisms and Malaria. Certain red blood cell disorders have been associated with innate protection against malaria infection. However many early studies were inconclusive. We intend to carry out a comprehensive study to investigate the effect of red blood cell differences on the invasion and/or growth of Plasmodium falciparum in vitro using improved techniques. Identification of red cell components involved in interaction with P.falciparum would give a better understanding of host ....Red Cell Polymorphisms and Malaria. Certain red blood cell disorders have been associated with innate protection against malaria infection. However many early studies were inconclusive. We intend to carry out a comprehensive study to investigate the effect of red blood cell differences on the invasion and/or growth of Plasmodium falciparum in vitro using improved techniques. Identification of red cell components involved in interaction with P.falciparum would give a better understanding of host parasite interactions which may in turn suggest novel approaches or pathways to persue. This may eventually lead to the development of novel therapeutics.
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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
Investigating the molecular basis of T-cell receptor cross-reactivity. This project will explore the basis of unexpected immune reactions whereby the immune system mistakes one molecular structure for another, a phenomenon known as cross-reactivity. This project will examine how often this is due to molecular mimicry, potentially explaining why immune T cells sometimes react inappropriately to different agents.
Glycointeractions. This project aims to characterise two new classes of structural interactions with carbohydrates: carbohydrate-carbohydrate interactions and short alpha helical domains which can bind carbohydrates. Carbohydrate structures are found on the surface of cells in all forms of life. The intended outcome is to understand the molecular basis for these carbohydrate interactions. This information should provide an intellectual framework for understanding and manipulating these carbohydr ....Glycointeractions. This project aims to characterise two new classes of structural interactions with carbohydrates: carbohydrate-carbohydrate interactions and short alpha helical domains which can bind carbohydrates. Carbohydrate structures are found on the surface of cells in all forms of life. The intended outcome is to understand the molecular basis for these carbohydrate interactions. This information should provide an intellectual framework for understanding and manipulating these carbohydrate interactions, which underpin many processes in biological systems. The findings will inform the design of future drugs to block these interactions and will generate new tools for glycoscience.Read moreRead less
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.