Investigation of a Novel Protein Implicated in Phosphate Metabolism in Bacteria. Phosphate is an important nutrient for all forms of life on Earth. A novel bacterial protein has been identified that appears to be important for the uptake or processing of phosphate, since mutants lacking the protein grow poorly inside certain cells of the human immune system (where phosphate levels are low) and in media containing low phosphate. The aims of this project are: to determine the role of the protein b ....Investigation of a Novel Protein Implicated in Phosphate Metabolism in Bacteria. Phosphate is an important nutrient for all forms of life on Earth. A novel bacterial protein has been identified that appears to be important for the uptake or processing of phosphate, since mutants lacking the protein grow poorly inside certain cells of the human immune system (where phosphate levels are low) and in media containing low phosphate. The aims of this project are: to determine the role of the protein by examining all phosphate containing molecules in our mutants; to determine its location in bacteria and functional domains; to identify other affected genes in our mutants; and, to find proteins that interact with this new protein. This project expects to demonstrate the importance of this protein in phosphate metabolism in bacteria.Read moreRead less
Structural studies of host-pathogen interactions. The host-pathogen interface represents a major frontier for biomedical and biotechnological applications. This project aims to understand at the atomic level two such interfaces. In the first instance, the project will elucidate the molecular basis for inhibition of premature host cell death by poxviruses, in particular vaccinia and variola virus, the causative agent of smallpox. In the second instance, the aim is to understand how defensins, a ....Structural studies of host-pathogen interactions. The host-pathogen interface represents a major frontier for biomedical and biotechnological applications. This project aims to understand at the atomic level two such interfaces. In the first instance, the project will elucidate the molecular basis for inhibition of premature host cell death by poxviruses, in particular vaccinia and variola virus, the causative agent of smallpox. In the second instance, the aim is to understand how defensins, a major class of host defence molecules, recognise microbial targets such as fungi, and exert a potent antimicrobial effect. Understanding the precise molecular mechanisms operating at both these host-pathogen interfaces this will provide novel avenues for the design of antiviral and antimicrobial agents.Read moreRead less
Molecular basis of synergy between PIs and defensins against fungi. The plant defensin nicotinamide adenine dinucleotide dehydrogenase subunit 1 (NaD1) has potent antifungal activity against agricultural and human pathogens and has potential in the treatment of serious diseases that affect crop production and human health. NaD1 has been found to permeabilise membranes and allows entry of other molecules into the fungal cytoplasm. While screening for molecules that enhance the activity of defensi ....Molecular basis of synergy between PIs and defensins against fungi. The plant defensin nicotinamide adenine dinucleotide dehydrogenase subunit 1 (NaD1) has potent antifungal activity against agricultural and human pathogens and has potential in the treatment of serious diseases that affect crop production and human health. NaD1 has been found to permeabilise membranes and allows entry of other molecules into the fungal cytoplasm. While screening for molecules that enhance the activity of defensins a number of proteinase inhibitors were identified that act synergistically with NaD1. This project aims to identify the molecular basis of this synergy which is expected to lead to better control of fungal diseases of crops and in humans.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE180100202
Funder
Australian Research Council
Funding Amount
$255,120.00
Summary
Three-dimensional cryo correlative light and electron microscopy facility. This project aims to establish a three-dimensional (3D) cryo-correlative light and electron microscopy facility. The facility will integrate light microscopy with high resolution cryo-electron tomography and 3D slice-and-view focused ion beam scanning electron microscopy. The open access facility should create new capabilities for Australian researchers to tag biological events and structures with fluorescence markers and ....Three-dimensional cryo correlative light and electron microscopy facility. This project aims to establish a three-dimensional (3D) cryo-correlative light and electron microscopy facility. The facility will integrate light microscopy with high resolution cryo-electron tomography and 3D slice-and-view focused ion beam scanning electron microscopy. The open access facility should create new capabilities for Australian researchers to tag biological events and structures with fluorescence markers and image them using the currently highest resolution 3D imaging techniques for biological matter. The facility expects to reveal fundamental insights into cell and structural biology, and help drive innovation in agriculture, pharmaceutics, and biomaterials.Read moreRead less
Host-pathogen interactions: the role of mimicry. The proposed research program, using a combination of structure and functional analysis will provide insight into the mechanism of nucleotide hydrolysis by the enzymes NTPDases. This study will not only improve our fundamental understanding of NTPDase action but could lead to the rational design of antimicrobials.
Structural and functional analysis of the protein kinase R. We have shown that protein kinase R (PKR) plays a key role in regulating the body's response to virus infections, inflammation and cancer. This project will identify mechanisms that regulate the activity of PKR and provide information useful for the development of novel drugs.
Programmed cell death in host-microbe interactions. This project aims to address how host cell death, as part of the immune defence system, controls invading microbes. By following host-microbe interactions at high resolution, the project will generate new knowledge in the area of infection and immunity based on an interdisciplinary approach to discover new cell death factors. The expected outcome of this project will enhance the imaging capacity and develop new technologies in Australia by buil ....Programmed cell death in host-microbe interactions. This project aims to address how host cell death, as part of the immune defence system, controls invading microbes. By following host-microbe interactions at high resolution, the project will generate new knowledge in the area of infection and immunity based on an interdisciplinary approach to discover new cell death factors. The expected outcome of this project will enhance the imaging capacity and develop new technologies in Australia by building on international collaborations, providing significant benefits to the health of the community and potential to develop innovative applications in biomedical industries.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.
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE180100001
Funder
Australian Research Council
Funding Amount
$345,475.00
Summary
Pushing the limits of fluorescence microscopy with adaptive optics. This project aims to establish an adaptive optics, super-resolution optical microscopy facility to image cellular events with the highest possible spatial resolution, in a whole cell or tissue context. Sophisticated computer-controlled deformable mirrors will be used to correct the way light is distorted as it passes through specimens, thereby overcoming aberrations found in thick and complex samples. This adaptive optics system ....Pushing the limits of fluorescence microscopy with adaptive optics. This project aims to establish an adaptive optics, super-resolution optical microscopy facility to image cellular events with the highest possible spatial resolution, in a whole cell or tissue context. Sophisticated computer-controlled deformable mirrors will be used to correct the way light is distorted as it passes through specimens, thereby overcoming aberrations found in thick and complex samples. This adaptive optics system will enable researchers to study complex behaviour of biological specimens, at the optical resolution limit in plant and animal tissues, leading to basic biology and biotechnology outcomes in biofuels, biomaterials and biomedicines.Read moreRead less
Australian Laureate Fellowships - Grant ID: FL150100106
Funder
Australian Research Council
Funding Amount
$2,951,945.00
Summary
Bio-metrology and modelling of a complex system: the malaria parasite. Bio-metrology and modelling of a complex system: the malaria parasite: This fellowship project aims to develop a cross-disciplinary program to measure, model and manipulate a complex cellular system — sexual differentiation of the human malaria parasite. Combining life and physical sciences with powerful imaging techniques, the project seeks to develop quantitative biochemical, biophysical and modelling techniques to probe a ....Bio-metrology and modelling of a complex system: the malaria parasite. Bio-metrology and modelling of a complex system: the malaria parasite: This fellowship project aims to develop a cross-disciplinary program to measure, model and manipulate a complex cellular system — sexual differentiation of the human malaria parasite. Combining life and physical sciences with powerful imaging techniques, the project seeks to develop quantitative biochemical, biophysical and modelling techniques to probe a complex system in a way previously not possible. It expects to integrate and correlate thousands of measurements of the dynamic processes inside cells and use these datasets to generate rigorous and sophisticated mathematical models that can predict drivers of commitment for transformation of the parasite to a sexual phase in preparation for transmission to mosquitoes. This holistic approach hopes to deliver new biotechnology and biomedical outcomes, including new ways to combat disease in livestock and humans.Read moreRead less