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Phage display derived antibody fragments for membrane protein research. Membrane proteins are key components of all living organisms and represent more than 50 per cent of all drug targets. This project will redefine the way membrane proteins are studied and will be highly beneficial to basic research, human disease and the biotechnology industry.
Multiscale Analysis Of Plasma Membrane Microdomains In Health And Disease
Funder
National Health and Medical Research Council
Funding Amount
$863,413.00
Summary
The cell surface encloses the cell in a protective barrier but it must also respond to signals coming from outside the cell. To accomplish this, the cell surface is made up of numerous regions each with a specialised role. This proposal aims to examine how lipids and proteins work together to make these specialised regions and aims to understand what goes wrong in diseases such as muscular dystrophy.
The mechanism of pore formation by Membrane Attack Complex/Perforin-like proteins. Members of the Membrane Attack Complex / Perforin (MACPF) family of proteins are essential for life, playing fundamental roles in immunity, tissue development and neuron formation. This project seeks to understand the basic mechanism of how MACPF proteins can form pores in target cells, a process central for killing in mammalian immunity.
A structural investigation into T cell signalling machines. The project aims to understand how receptor recognition events cause intracellular signalling.Membrane-bound receptors, their cognate ligands and the ensuing intracellular activation signal determine cellular fate. The project will explore events central to cellular immunity by examining the T cell signalling machinery. This project will use labelling, crystallographic and cryo-electron microscopy studies, to determine the molecular arc ....A structural investigation into T cell signalling machines. The project aims to understand how receptor recognition events cause intracellular signalling.Membrane-bound receptors, their cognate ligands and the ensuing intracellular activation signal determine cellular fate. The project will explore events central to cellular immunity by examining the T cell signalling machinery. This project will use labelling, crystallographic and cryo-electron microscopy studies, to determine the molecular architecture of the T cell receptor (TCR) CD3 complex, a molecular machine central to T cell signalling. This project should reveal how antigen recognition leads to T cell signal transduction which will create jobs, bring substantial health benefits and improve quality of life for Australians.Read moreRead less
A structural and molecular investigation into the basic mechanism of T cell receptor complex function. Cellular fate is determined by interactions between membrane-bound receptors and their cognate ligands. The basic mechanism of how such receptor-mediated recognition events cause intracellular signalling is poorly understood in most biological systems, including the cellular immune recognition axis. This project will explore events central to cellular immunity by examining the interactions cent ....A structural and molecular investigation into the basic mechanism of T cell receptor complex function. Cellular fate is determined by interactions between membrane-bound receptors and their cognate ligands. The basic mechanism of how such receptor-mediated recognition events cause intracellular signalling is poorly understood in most biological systems, including the cellular immune recognition axis. This project will explore events central to cellular immunity by examining the interactions centred on T-cell receptor complexes. This project will explore the molecular mechanisms underpinning these key receptor-recognition events and relate these observations to T-cell activation. The proposal will shed fundamental insight into Major Histocompatibility Complex restriction, T-cell development and how antigen recognition leads to T-cell signal transduction. Read moreRead less
Understanding how a family of chloride pumps and channels are regulated. This project examines how a major family of chloride channels and pumps, found in nearly all organisms, works at the molecular level and how it is modulated by chemical signals from within cells. The expected outcomes are to demonstrate novel mechanisms general to these essential proteins and to provide fundamental insights in understanding vital physiological processes across all kingdoms of life. Ultimately, this work aim ....Understanding how a family of chloride pumps and channels are regulated. This project examines how a major family of chloride channels and pumps, found in nearly all organisms, works at the molecular level and how it is modulated by chemical signals from within cells. The expected outcomes are to demonstrate novel mechanisms general to these essential proteins and to provide fundamental insights in understanding vital physiological processes across all kingdoms of life. Ultimately, this work aims to lead to the development of novel engineered proteins that can act as sub-microscopic electrical 'switches' and highly specific sensors for a variety of molecules for nanotechnology and biotechnology applications.Read moreRead less
Lipid droplet membrane tethers at atomic resolution. Eukaryotic cells are distinguished by the presence of membrane-bound compartments called organelles. This project will use structural biology to determine how essential proteins called sorting nexins (SNXs) regulate membrane interactions required for lipid droplet formation. These interactions are essential for life, controlling protein and lipid homeostasis needed for cell survival. The major outcome of this proposal will be a fundamental und ....Lipid droplet membrane tethers at atomic resolution. Eukaryotic cells are distinguished by the presence of membrane-bound compartments called organelles. This project will use structural biology to determine how essential proteins called sorting nexins (SNXs) regulate membrane interactions required for lipid droplet formation. These interactions are essential for life, controlling protein and lipid homeostasis needed for cell survival. The major outcome of this proposal will be a fundamental understanding of how SNXs control this process, and the work will significantly strengthen our international collaboration in this emerging area. The knowledge has potential future translation in the treatment of neurodegenerative disorders where dysregulation of these proteins is known to cause disease.Read moreRead less
Control of selective microRNA release via exosomes and microvesicles. This project aims to improve our understanding of cell-to-cell communication. Cells release genetic material including microRNAs in lipid membrane-enclosed vesicles (called exosomes and microvesicles) to alter neighbouring and distant cells. Recent research shows that the contents of these vesicles are regulated by cell state, however, the molecular mechanisms are not yet known. This project will investigate the hypothesis tha ....Control of selective microRNA release via exosomes and microvesicles. This project aims to improve our understanding of cell-to-cell communication. Cells release genetic material including microRNAs in lipid membrane-enclosed vesicles (called exosomes and microvesicles) to alter neighbouring and distant cells. Recent research shows that the contents of these vesicles are regulated by cell state, however, the molecular mechanisms are not yet known. This project will investigate the hypothesis that changes in the RNA-binding protein composition of cholesterol-rich membranes mediate the selection of miRNA loaded in the vesicles. This knowledge may increase our understanding of mechanisms of disease because this mode of cell-to-cell communication is disrupted or hijacked in pathologies. Future translation in diverse applications may improve human, animal and plant health.Read moreRead less
Imaging the T cell signalling machinery . The conversion of external stimuli to the interior of a cell is a fundamental process that underpins many unique facets of biology, including cellular movement, nerve transmission, response to hormones and immune recognition. However, the basic mechanism by which such signals are transmitted across cellular membranes is poorly understood. This proposal will seek to bridge this gap in our knowledge by imaging a multi-component “decision-making” machine th ....Imaging the T cell signalling machinery . The conversion of external stimuli to the interior of a cell is a fundamental process that underpins many unique facets of biology, including cellular movement, nerve transmission, response to hormones and immune recognition. However, the basic mechanism by which such signals are transmitted across cellular membranes is poorly understood. This proposal will seek to bridge this gap in our knowledge by imaging a multi-component “decision-making” machine that controls whether or not the immune system becomes activated. Accordingly, this proposal will provide far-reaching insights into molecular events that are of central importance to the initiation of immunity, and thus will ultimately benefit society via improvements in health.Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE180101165
Funder
Australian Research Council
Funding Amount
$365,058.00
Summary
Structural insights into adenosine receptors. This project aims to investigate mechanisms underlying ligand binding and signal transduction at G protein-coupled receptors (GPCRs) by utilising the adenosine receptor family as a model system. This interdisciplinary project will use structural biology, pharmacology and biochemistry. The expected outcomes include understanding ligand selectivity across the four adenosine receptor family members. This should provide significant benefits, such as adva ....Structural insights into adenosine receptors. This project aims to investigate mechanisms underlying ligand binding and signal transduction at G protein-coupled receptors (GPCRs) by utilising the adenosine receptor family as a model system. This interdisciplinary project will use structural biology, pharmacology and biochemistry. The expected outcomes include understanding ligand selectivity across the four adenosine receptor family members. This should provide significant benefits, such as advancement of fundamental knowledge that could also lead to therapeutic development.Read moreRead less