The role of phosphoinositides in endosomal maturation dynamics. This project aims to investigate the regulation of an intracellular compartment within a cell called endosomes, which plays critical roles in cellular homeostasis, signalling and pathogen entry. New knowledge is expected to be generated in understanding endosome maturation and the signalling events that drive this process using a unique, multidisciplinary approach combining state of the art imaging techniques and high throughput pro ....The role of phosphoinositides in endosomal maturation dynamics. This project aims to investigate the regulation of an intracellular compartment within a cell called endosomes, which plays critical roles in cellular homeostasis, signalling and pathogen entry. New knowledge is expected to be generated in understanding endosome maturation and the signalling events that drive this process using a unique, multidisciplinary approach combining state of the art imaging techniques and high throughput protein analysis. The anticipated outcomes will be to define the molecular steps that govern the membrane-bound machinery on endosomes that directs endosomal maturation. This should provide significant benefits in delineating a process that is linked to almost all aspects of cell life.Read moreRead less
Probing sexual transformation of the human malaria parasite, Plasmodium falciparum, using novel imaging modalities. Malaria parasites adopt a characteristic banana shape prior to sexual recombination; without this shape change disease transmission via mosquitoes cannot occur. This project will use advanced imaging technologies to study sexual recombination of malaria with a view to preventing the millions of deaths due to malaria each year.
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.
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.
Formation of the Chlamydial Inclusion Requires Host Trafficking Pathways. Using cellular and biochemical approaches this project aims to examine the membrane trafficking pathways hijacked by the pathogen Chlamydia and to define the key components of these pathways. Chlamydia are obligate intracellular pathogens responsible for a range of human and animal diseases. In order to survive within the host cell, the pathogen hijacks the host's membrane trafficking pathways to engineer an intracellular ....Formation of the Chlamydial Inclusion Requires Host Trafficking Pathways. Using cellular and biochemical approaches this project aims to examine the membrane trafficking pathways hijacked by the pathogen Chlamydia and to define the key components of these pathways. Chlamydia are obligate intracellular pathogens responsible for a range of human and animal diseases. In order to survive within the host cell, the pathogen hijacks the host's membrane trafficking pathways to engineer an intracellular niche called an inclusion. In addition to providing a permissive environment, this strategy also shields the pathogen from the host's immune system.Read moreRead less
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.
New targets for antiviral therapies. The ability of dangerous viruses to cause lethal disease depends on their capacity to evade the immune system of infected hosts. This project will uncover at the molecular level the strategies used by viruses to disable immune responses; this will identify new ways to treat incurable diseases, by disabling the virus' defences against the immune system.