Discovery Early Career Researcher Award - Grant ID: DE160100293
Funder
Australian Research Council
Funding Amount
$372,000.00
Summary
Cracking the phosphoinositide code. This project seeks to determine how protein interactions with membrane lipids regulate recruitment to cellular organelles, providing new insight into the complex pathways of cellular homeostasis. Controlling the distribution of proteins within cells is critical for cell signalling and membrane trafficking. This is orchestrated by the interaction of specific protein modules with lipids on the surface of different organelles. The phox homology (PX) domain is a l ....Cracking the phosphoinositide code. This project seeks to determine how protein interactions with membrane lipids regulate recruitment to cellular organelles, providing new insight into the complex pathways of cellular homeostasis. Controlling the distribution of proteins within cells is critical for cell signalling and membrane trafficking. This is orchestrated by the interaction of specific protein modules with lipids on the surface of different organelles. The phox homology (PX) domain is a lipid-binding module found in numerous proteins essential for normal cell trafficking and homeostasis, and perturbed in many conditions including immune dysfunction and cancer. This project plans to investigate molecular determinants of PX-lipid association, generating knowledge about protein-membrane interactions required for cellular function. These insights may underpin future drug design.Read moreRead less
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
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.
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
Defining the molecular mechanisms of intracellular protein trafficking. Intracellular trafficking of proteins is critical for normal cell function and defects can lead to many different human diseases. Outcomes from this project will lead to insights into how trafficking is regulated at the atomic level and will help place Australia at the forefront of international efforts to understand this essential process.
A role for the actin cytoskeleton in suppression of prion pathology in yeast. The discovery that proteins as well as DNA carry genetic information is leading to a re-think of the mechanisms that program cell behaviour. There is a link between proteins that suppress cancer and protein inheritance. This project explores how heritable changes in proteins control cell behaviour and the implications of this for the origin of cancer.
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
How membrane-sensing proteins regulate synaptic vesicle endocytosis. This project aims to elucidate the molecular basis of how membrane-sensing proteins regulate synaptic vesicle endocytosis in mammalian central neurons. Nerve cells’ ability to transmit cellular information to one another is important for normal brain function. Efficient communication between neurons through sustained neurotransmitter release relies on the continuous supply of synaptic vesicles in presynaptic nerve terminals. Ke ....How membrane-sensing proteins regulate synaptic vesicle endocytosis. This project aims to elucidate the molecular basis of how membrane-sensing proteins regulate synaptic vesicle endocytosis in mammalian central neurons. Nerve cells’ ability to transmit cellular information to one another is important for normal brain function. Efficient communication between neurons through sustained neurotransmitter release relies on the continuous supply of synaptic vesicles in presynaptic nerve terminals. Key to this process are membrane dynamics during synaptic vesicle retrieval, but the precise underlying mechanisms are not well understood. The intended outcome of this project is insights into the molecular mechanisms of synaptic transmission, the fundamental process of brain function, increasing understanding of physiological processes such as muscle movement, vision, hearing, touch, learning and memory.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE130100078
Funder
Australian Research Council
Funding Amount
$800,000.00
Summary
Live molecular imaging using super resolution microscopy, two photon and spinning disk confocal microscopy. With recent developments of super-resolution microscopy it is now feasible to image single molecules within the cellular environment in living cells. Such insight is key to understanding basic biological interactions that govern the wiring of our brain, communications between cells and neurons and cell-cell adhesion.