Determination of cellular mechanisms underpinning cancer cell metastasis through integrated in vivo imaging approaches. Understanding key steps that drive the spread of cancer is critical to improve current treatment strategies. Using cutting-edge imaging technology and in vivo model systems that mimic the disease, this project will pinpoint key events that are susceptible to drug intervention and identify new therapeutic targets.
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE150100149
Funder
Australian Research Council
Funding Amount
$590,000.00
Summary
Reaching new heights in high-resolution electron microscopy . High-resolution electron microscopy (EM): Direct electron detection cameras are a recent technological breakthrough delivering one of the greatest single advancements to the field of molecular cryo-EM. The aim of this project is to enable a 'first of a kind' cryo-EM platform in Australia enabling high-throughput atomic resolution protein structure determination. This will be achieved by integrating a state-of-the-art Gatan K2 Summit D ....Reaching new heights in high-resolution electron microscopy . High-resolution electron microscopy (EM): Direct electron detection cameras are a recent technological breakthrough delivering one of the greatest single advancements to the field of molecular cryo-EM. The aim of this project is to enable a 'first of a kind' cryo-EM platform in Australia enabling high-throughput atomic resolution protein structure determination. This will be achieved by integrating a state-of-the-art Gatan K2 Summit Direct Electron Detection camera system into the established cryo-EM facility managed by the University of Queensland node of the Australian Microscopy and Microanalysis Facility. This will offer unique and significantly improved capabilities for atomic resolution protein structure analysis, and will support a broad range of projects across the biological sciences.Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE140101788
Funder
Australian Research Council
Funding Amount
$358,920.00
Summary
Structural Analysis of Biomolecular Complexes at Membrane Interfaces Important to Health and Disease. This project will study structural aspects of key biomolecular complexes at membrane interfaces that are involved with apoptosis (programmed cell death). Malfunctions in apoptosis have been implicated in many aliments including age-related diseases and cancers. Understanding of the molecular and structural aspects of key complexes can pave the way to novel therapies. The approach that will be us ....Structural Analysis of Biomolecular Complexes at Membrane Interfaces Important to Health and Disease. This project will study structural aspects of key biomolecular complexes at membrane interfaces that are involved with apoptosis (programmed cell death). Malfunctions in apoptosis have been implicated in many aliments including age-related diseases and cancers. Understanding of the molecular and structural aspects of key complexes can pave the way to novel therapies. The approach that will be used is to design new biomimetic outer mitochondrial membranes and use these to study the structure and binding of proteins involved with apoptosis. By studying simple models of complex systems, this project promises to yield detailed information on important biomolecular complexes where structural detail is currently lacking. Read moreRead less
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.
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
Structure and function of human zinc transporter membrane proteins. The aim of this project is to create fundamental new knowledge on how important mammalian membrane proteins operate. Membrane proteins are key drug targets and are significantly under-represented in structural databases. The project plans to combine innovative membrane protein screening technology with gene expression, structural biology, biophysics and cell biology. The project outcomes may elucidate specific molecular mechanis ....Structure and function of human zinc transporter membrane proteins. The aim of this project is to create fundamental new knowledge on how important mammalian membrane proteins operate. Membrane proteins are key drug targets and are significantly under-represented in structural databases. The project plans to combine innovative membrane protein screening technology with gene expression, structural biology, biophysics and cell biology. The project outcomes may elucidate specific molecular mechanisms underpinning the essential biological process of zinc homeostasis.Read moreRead less
Why is the peribacteroid membrane transcription factor SAT1 required for legume nitrogen fixation and what is its role in other symbiotic systems? This project will investigate the functional activity of the plant membrane bound basic helix-loop-helix (bHLH) transcription factor SAT1 in both nitrogen fixing (Rhizobia) and phosphorus acquiring (Arbuscular Mycorrhizal) symbioses found in plants. The project will identify its regulation and downstream activities across both symbiosis using selected ....Why is the peribacteroid membrane transcription factor SAT1 required for legume nitrogen fixation and what is its role in other symbiotic systems? This project will investigate the functional activity of the plant membrane bound basic helix-loop-helix (bHLH) transcription factor SAT1 in both nitrogen fixing (Rhizobia) and phosphorus acquiring (Arbuscular Mycorrhizal) symbioses found in plants. The project will identify its regulation and downstream activities across both symbiosis using selected legumes and or cereals.Read moreRead less
Investigating the structure of a T cell immune checkpoint molecule. This project aims to investigate the basic structure and function of a key co-receptor expressed on T cells, known as lymphocyte activation gene-3. T cells play a role in the immune system but must be managed to prevent autoimmunity. Insight into the function of the lymphocyte activation gene-3 function can be used to tailor immunotherapeutics to treat a variety of diseases, including cancer. Functionality of the T cell recept ....Investigating the structure of a T cell immune checkpoint molecule. This project aims to investigate the basic structure and function of a key co-receptor expressed on T cells, known as lymphocyte activation gene-3. T cells play a role in the immune system but must be managed to prevent autoimmunity. Insight into the function of the lymphocyte activation gene-3 function can be used to tailor immunotherapeutics to treat a variety of diseases, including cancer. Functionality of the T cell receptor is determined by utilising structural biology and cellular immunology techniques. The impact of this project effects the development of innovative T cell immunomodulatory agents, improving the health and quality of life of the Australian population.Read moreRead less
A unified model of amino acid homeostasis. This project aims to develop a unified model of amino acid homeostasis in mammalian cells and apply it to brain cells. The model will be underpinned by a mathematical algorithm that allows predicting amino acid levels in the cytosol based on fundamental parameters such as transport and metabolism. This project should provide the significant benefit of enabling the prediction of essential functions such as cell growth and survival.
Molecular interactions in cell membranes. Cell membranes are a complex composite of proteins and lipids and we have only a rough idea about how they perform their many functions. Together with Leica Microsystems, this project will develop a new microscope that can map the molecular interactions within the membrane revealing details that have never been seen before.