I am a cell biologist investigating the means by which intracellular compartmentalization of signalling proteins determines signalling outcomes and cell fate. I focus particularly on signals that regulate immune function and cancer progression.
Autophagy: A New Pathway For Presenting Antigen In Dendritic Cells.
Funder
National Health and Medical Research Council
Funding Amount
$444,973.00
Summary
Microbes are chopped up and digested before being displayed to the immune system. Here we will investigate a new pathway termed _autophagy� that helps cells to digest material for immune display.
A tale of two genomes: integrating mitochondrial biogenesis into the cell cycle and metabolic control. The human genome is cordoned into two distinct compartments in our cells. Most genes are in the nucleus, while a distinct set of genes are held within our mitochondria. Using yeast as a model organism, this project will provide a holistic view of how expression of the two genomes is coordinated.
Characterisation of membrane protein ubiquitination by MARCH ligases. The goal of the project is to understand how a family of enzymes called MARCHs regulate expression and localisation of immunoregulatory receptors within cells by post-translational addition of a small protein tag called Ubiquitin. The aims are to decipher the ubiquitination patterns produced by the MARCHs; identify the E2 ligases used by the MARCHs to produce distinct Ub codes; and apply a new proteomic pipeline to identify no ....Characterisation of membrane protein ubiquitination by MARCH ligases. The goal of the project is to understand how a family of enzymes called MARCHs regulate expression and localisation of immunoregulatory receptors within cells by post-translational addition of a small protein tag called Ubiquitin. The aims are to decipher the ubiquitination patterns produced by the MARCHs; identify the E2 ligases used by the MARCHs to produce distinct Ub codes; and apply a new proteomic pipeline to identify novel representative MARCH substrates in mice deficient in six different MARCHs. It is anticipated the project will reveal novel insights into a fundamental cell biological process of major significance for regulation of protein expression and trafficking in cells of the immune system.Read moreRead less
Defining the membrane protein cargo transported by Retromer. This project aims to define the role of Retromer, a protein machine that directs the organisation and movement of proteins within the cell. The function of proteins is dependent on how they travel through the various regions or compartments within the cell. One intracellular compartment, termed endosomes, is central to this dynamic process. Intracellular transport of biomolecules through the endosomal organelle is critical for normal c ....Defining the membrane protein cargo transported by Retromer. This project aims to define the role of Retromer, a protein machine that directs the organisation and movement of proteins within the cell. The function of proteins is dependent on how they travel through the various regions or compartments within the cell. One intracellular compartment, termed endosomes, is central to this dynamic process. Intracellular transport of biomolecules through the endosomal organelle is critical for normal cellular processes such as signalling and development. Endosomal transport occurs within membrane domains and membrane vesicular carriers formed by Retromer. This project aims to define the transmembrane proteins sorted by the distinct retromer complexes that form within the cell and the sorting signals essential for their correct trafficking and localisation.Read moreRead less
Membrane trafficking and endosome to trans-Golgi network retrograde pathways. This project will study newly discovered and essential transport highways in cells, which connect the secretory and internalisation pathways. This research will enhance understandings of how molecules are transported along specific highways in cells. By training students, the project will contribute to the expertise of cell biology in Australia.
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
Characterizing the regulators of mitochondrial biogenesis in Arabidopsis thaliana. The overall aim of this project is to identify and characterise the underlying regulatory factors that control mitochondrial mass and number in plants. The project will exploit a regulatory mechanism that links the mitochondrial import machinery and the respiratory chain. Utilising both forward and reverse genetic approaches, the abundances of protein import translocases will be altered and the changes to mitochon ....Characterizing the regulators of mitochondrial biogenesis in Arabidopsis thaliana. The overall aim of this project is to identify and characterise the underlying regulatory factors that control mitochondrial mass and number in plants. The project will exploit a regulatory mechanism that links the mitochondrial import machinery and the respiratory chain. Utilising both forward and reverse genetic approaches, the abundances of protein import translocases will be altered and the changes to mitochondrial biogenesis will be investigated. This will identify regulatory factors, which can be manipulated and used to alter mitochondrial number and activity.Read moreRead less
Phosphoinositide regulation of lysosome reformation during autophagy. This project aims to investigate a new critical step in the autophagy pathway, autophagic lysosome reformation, a fundamental, evolutionarily conserved mechanism for cellular homeostasis. By combining gene function studies with advanced cellular imaging techniques, this project will investigate the dynamic membrane changes that drive this lysosome recycling pathway and how it is regulated by a hierarchical succession of specif ....Phosphoinositide regulation of lysosome reformation during autophagy. This project aims to investigate a new critical step in the autophagy pathway, autophagic lysosome reformation, a fundamental, evolutionarily conserved mechanism for cellular homeostasis. By combining gene function studies with advanced cellular imaging techniques, this project will investigate the dynamic membrane changes that drive this lysosome recycling pathway and how it is regulated by a hierarchical succession of specific enzymes. The expected outcome will be to re-define the archetypical autophagy pathway and characterise novel mechanisms by which it is controlled. This project will reveal new fundamental biological processes, and act as a framework for developing new imaging modalities and tools for studying autophagy.Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE170100575
Funder
Australian Research Council
Funding Amount
$372,000.00
Summary
Pathogen detection in mammals. This project aims to study the role of a host molecule in immune protection. Multicellular organisms need to recognise pathogens to initiate immune protection. To do this, pathogen-specific molecules are presented to the immune system causing activation. Recently a mode of pathogen recognition was discovered in mammals. As microbes synthesise essential vitamins, they release tell-tale metabolite by-products, which a host molecule called MR1 captures and presents to ....Pathogen detection in mammals. This project aims to study the role of a host molecule in immune protection. Multicellular organisms need to recognise pathogens to initiate immune protection. To do this, pathogen-specific molecules are presented to the immune system causing activation. Recently a mode of pathogen recognition was discovered in mammals. As microbes synthesise essential vitamins, they release tell-tale metabolite by-products, which a host molecule called MR1 captures and presents to white blood cells. However, it is not understood how MR1 accomplishes this, the cellular machinery required, or how the metabolites are guided to MR1. Understanding this process is expected to explain microbial pathogen recognition.Read moreRead less