Expression and substrate recognition by MARCH ubiquitin ligases. Eukaryotic cells are compartmentalised, with different organelles playing distinct functions. This project will characterise the MARCHs, proteins which control the localisation and half-life of other proteins. Understanding how the MARCHs work will provide novel insights into fundamental cellular processes that play major roles in many biological functions.
SNARE-mediated perforin and cytokine release in natural killer cells. Cytotoxic cells release toxic granules and cytokine messengers to kill pathogen infected and cancerous cells and to mount immune responses. This project will investigate different SNARE molecules that regulate the secretion of perforin from granules and cytokines from other carriers, assisting in the understanding of complex but essential cellular pathways.
Subcellular Trafficking Of P Proteins Of Human Pathogenic Viruses: Roles In Viral Pathogenicity And Targeting For Therapeutics
Funder
National Health and Medical Research Council
Funding Amount
$578,352.00
Summary
In order to infect humans, pathogenic viruses such as rabies, Nipah, Hendra and Australian bat lyssavirus must be able to evade the immune response. To do this, viruses produce "interferon antagonists" that interfere with specific immune processes by mechanisms that are not fully understood. Our study will characterise the mechanisms used by rabies and other viruses to block immunity, and identify strategies to disable viral immune evasion, rendering these lethal viruses susceptible to destructi ....In order to infect humans, pathogenic viruses such as rabies, Nipah, Hendra and Australian bat lyssavirus must be able to evade the immune response. To do this, viruses produce "interferon antagonists" that interfere with specific immune processes by mechanisms that are not fully understood. Our study will characterise the mechanisms used by rabies and other viruses to block immunity, and identify strategies to disable viral immune evasion, rendering these lethal viruses susceptible to destruction by the human immune system.Read moreRead less
Sorting Out The Synapse: The Role Of Intracellular Trafficking In NMDA Receptor Homeostasis
Funder
National Health and Medical Research Council
Funding Amount
$631,966.00
Summary
When the normal levels of cell surface proteins in neurons are reduced this can lead to a variety of debilitating neurodegenerative and neuronal diseases. These levels are maintained by organelles inside the neuron called endosomes. In this project we will examine how cell surface receptors required for synapse formation are transported through endosomes by a protein machine called retromer, which is important in both Alzheimer’s and Parkinson’s disease.
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
Organising Intracellular Compartments by Formation of Transport Carriers. This project aims to investigate the cellular components which generate carriers that transport material between compartments within the cell. The process of sorting proteins and sending them to the right place is a fundamental mechanism critical to understand how individual proteins function as the move around within cells. The generated knowledge about how cells organise themselves through the movement of proteins betwee ....Organising Intracellular Compartments by Formation of Transport Carriers. This project aims to investigate the cellular components which generate carriers that transport material between compartments within the cell. The process of sorting proteins and sending them to the right place is a fundamental mechanism critical to understand how individual proteins function as the move around within cells. The generated knowledge about how cells organise themselves through the movement of proteins between endosomal intracellular compartments will provide significant benefits by enhancing our capacity to understand this conserved cellular pathway which ensures the integrity of all cellular processes including signalling, communication, homeostasis and development.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.
Australian Laureate Fellowships - Grant ID: FL210100107
Funder
Australian Research Council
Funding Amount
$2,960,000.00
Summary
Tracking nanoparticles: from cell culture to in vivo delivery. Understanding how cells function in the ‘real-time’ context of a living organism is a key challenge in the new era of cell biology. Using super-resolution light microscopy and state-of-the-art correlative electron microscopy together with model systems, this Fellowship aims to deliver new understandings of cells in their natural environment. Significantly, the project will elucidate how proteins or nanoparticles pass from the bloodst ....Tracking nanoparticles: from cell culture to in vivo delivery. Understanding how cells function in the ‘real-time’ context of a living organism is a key challenge in the new era of cell biology. Using super-resolution light microscopy and state-of-the-art correlative electron microscopy together with model systems, this Fellowship aims to deliver new understandings of cells in their natural environment. Significantly, the project will elucidate how proteins or nanoparticles pass from the bloodstream into tissues and then into cells, and in doing so deliver much-needed knowledge of protein and particle trafficking in situ. Outcomes and benefits include leading-edge fundamental science into the function of cells, education, outreach and building of Australian capacity in high-demand skill sets.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