Cytotoxic lymphocytes are immune cells responsible for the killing infected or cancerous cells. How cytotoxic lymphocytes mature from a naive inactive to a fully activated state as they encounter infected or malignant cells is poorly understood, and will be investigated in the current proposal. Our results will aid in the development of novel therapies for cancer and other immunological diseases.
Manipulation of mitochondrial function by Legionella pneumophila. . The intracellular bacterial pathogen Legionella pneumophila co-evolved with eukaryotic hosts and has developed sophisticated mechanisms to manipulate human cell function – mitochondria in particular – by secreting >300 effector proteins through a specialised Type-IV system into the host cell. This research aims to understand the function of effector proteins targeted to mitochondria; delivering important new knowledge in host-pa ....Manipulation of mitochondrial function by Legionella pneumophila. . The intracellular bacterial pathogen Legionella pneumophila co-evolved with eukaryotic hosts and has developed sophisticated mechanisms to manipulate human cell function – mitochondria in particular – by secreting >300 effector proteins through a specialised Type-IV system into the host cell. This research aims to understand the function of effector proteins targeted to mitochondria; delivering important new knowledge in host-pathogen and mitochondrial biology and advanced cell biology tools. With most of the effector proteins yet to be characterised, benefits from the project will be to reveal specifically how these target mitochondria, and more broadly, how bacterial pathogens manipulate organelles for their survival.Read moreRead less
Deadly Commute - Targeting The Trafficking Mechanisms That Licence Inflammatory Cell Death
Funder
National Health and Medical Research Council
Funding Amount
$774,544.00
Summary
MLKL is a protein naturally found inside cells. MLKL is activated by inflammation. Once activated, MLKL relocates to the outer periphery of cells and kills them. Gut cells are especially vulnerable to death-by-MLKL and this problem causes Inflammatory Bowel Disease. Using cutting edge microscopy, we have discovered how MLKL moves to the periphery of cells prior to killing them. We will test if blocking this movement of MLKL to the cell periphery stops gut death and Inflammatory Bowel Disease.
Discovery Early Career Researcher Award - Grant ID: DE120102263
Funder
Australian Research Council
Funding Amount
$375,000.00
Summary
Export of effector proteins by P. falciparum to the infected red blood cell. Infection by the malaria parasite has lethal consequences for humans. The parasite exports hundreds of proteins via a translocon to commandeer the red blood cell. This project aims to determine the function of one of the major translocon components and determine if it is a viable target for anti-malarial drug development.
The function of the ribbon structure of the Golgi apparatus in vertebrates. The aim of the project is to determine the function of the Golgi ribbon structure in higher order cell functions, including metabolism, cell cycle, and cell polarity in both cultured cells and whole organisms. Understanding of the functions of the Golgi has been restricted to the regulation of glycosylation and membrane transport. However, it is now recognised that the Golgi apparatus feeds into the wiring of a range of ....The function of the ribbon structure of the Golgi apparatus in vertebrates. The aim of the project is to determine the function of the Golgi ribbon structure in higher order cell functions, including metabolism, cell cycle, and cell polarity in both cultured cells and whole organisms. Understanding of the functions of the Golgi has been restricted to the regulation of glycosylation and membrane transport. However, it is now recognised that the Golgi apparatus feeds into the wiring of a range of cellular networks in higher organisms such as cell polarisation, directed migration, metabolism and autophagy. Vertebrates have evolved mechanisms for joining individual Golgi stacks into a ribbon structure. The relevance of this ribbon structure remains a mystery. The project aims to answer this major question in cell biology.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE130100090
Funder
Australian Research Council
Funding Amount
$700,000.00
Summary
Three-dimensional cryo electron microscopy facility. The three-dimensional cryo-electron microscopy facility will let us visualise plants, pathogens and nanomachines with resolution not previously possible allowing us to see into cells and diseases with vastly more detail. Our world-class experts will provide regional and national researchers access to cutting-edge technology complementary to the Australian Synchrotron.
Mapping the integration of T cell fate control across time and space. This project aims to apply new methods to determine how coordination of signalling complexes impacts upon the fate of cells of the adaptive immune system. It expects to determine how the context of signallng orchestrates cell fates such as differentiation, death and proliferation. The project is expected to yield an experimental and analytical platform for further investigations into a broad range of biological questions, and ....Mapping the integration of T cell fate control across time and space. This project aims to apply new methods to determine how coordination of signalling complexes impacts upon the fate of cells of the adaptive immune system. It expects to determine how the context of signallng orchestrates cell fates such as differentiation, death and proliferation. The project is expected to yield an experimental and analytical platform for further investigations into a broad range of biological questions, and to provide new knowledge of this fundamental problem. This platform should support further work that ultimately provides new models for tissue and immune cell regeneration, and new manufacturing platforms for therapies for humans and livestock, among other benefits.Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE120100794
Funder
Australian Research Council
Funding Amount
$375,000.00
Summary
Revealing dynamic mechanisms controlling pluripotency in mammalian stem cells and embryos. Every cell of our mature bodies originates from 'pluripotent' cells present in the early mammalian embryo. These cells can be captured and grown in plastic dishes. The project will use imaging methods to reveal how gene regulatory molecules control pluripotent cells in the embryo and in culture.
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE180100157
Funder
Australian Research Council
Funding Amount
$600,000.00
Summary
Confocal and single molecule microscopes for systems microscopy. This project aims to establish Australia’s first system microscopy facility with dedicated live-cell confocal and single-molecule fluorescence microscopes. In systems microscopy, the imaging workflow is automated so that large and unbiased data sets of the spatiotemporal organisation of molecules and cells can be generated. Combined with statistical and bioinformatics analyses, image-derived data provides system-wide information th ....Confocal and single molecule microscopes for systems microscopy. This project aims to establish Australia’s first system microscopy facility with dedicated live-cell confocal and single-molecule fluorescence microscopes. In systems microscopy, the imaging workflow is automated so that large and unbiased data sets of the spatiotemporal organisation of molecules and cells can be generated. Combined with statistical and bioinformatics analyses, image-derived data provides system-wide information that is not easily obtainable with other approaches. The project will enable Australian researchers to image and analyse the full complexity of biological systems, potentially transforming cell biology, drug development and understanding the molecular basis of disease. It will also demonstrate how the capacity of microscopy facilities can be enhanced and bias in imaging data reduced by automating data acquisition and mining of image-based data.Read moreRead less