Role Of Exported Proteins In Malaria Parasite Development In The Liver
Funder
National Health and Medical Research Council
Funding Amount
$520,613.00
Summary
Each year over 250 million people contract malaria and over 1 million die. The key to the malaria parasite’s success is the ability to live inside host cells, including hepatocytes and erythrocytes. Here, we aim to determine how the malaria parasite lives within hepatocytes, to engineer mutant parasites that can no longer do so and to assess whether mutant parasites confer protection against future malaria. Our program will use the most virulent human parasite P. falciparum and the rodent parasi ....Each year over 250 million people contract malaria and over 1 million die. The key to the malaria parasite’s success is the ability to live inside host cells, including hepatocytes and erythrocytes. Here, we aim to determine how the malaria parasite lives within hepatocytes, to engineer mutant parasites that can no longer do so and to assess whether mutant parasites confer protection against future malaria. Our program will use the most virulent human parasite P. falciparum and the rodent parasite P. berghei.Read moreRead less
Many bacterial pathogens invade host cells to replicate and avoid detection by the host. These pathogens interact with the host and by manipulating it to its benefit they establish an environment to survive in. A detailed understanding of the targeted hosts pathways and which are essential for pathogen survival is knowledge that will allow future development of therapeutic intervention strategies.
Function And Inhibition Of Plasmepsin V In Targeting Malaria Virulence Proteins Into Human Erythrocytes
Funder
National Health and Medical Research Council
Funding Amount
$407,845.00
Summary
Malaria parasites dramatically renovate infected erythrocytes to survive and evade the host immune system by delivering hundreds of exported parasite proteins into the cell. The parasite protease Plasmepsin V is essential for protein export. We aim to develop potent inhibitors of this protease in the hope of blocking its function and killing the parasite. We also aim to discover the components of the trafficking pathway after cleavage by Plasmepsin V that sorts virulence proteins to the host cel ....Malaria parasites dramatically renovate infected erythrocytes to survive and evade the host immune system by delivering hundreds of exported parasite proteins into the cell. The parasite protease Plasmepsin V is essential for protein export. We aim to develop potent inhibitors of this protease in the hope of blocking its function and killing the parasite. We also aim to discover the components of the trafficking pathway after cleavage by Plasmepsin V that sorts virulence proteins to the host cell.Read moreRead less
Understanding the basic biology of cells will allow us to pinpoint key mechanisms and molecules that underpin multiple diseases and are targets for treatments. The broad aims of this research program include the development of new therapies for chronic inflammatory diseases, understanding how proteins are sorted and trafficked inside cells in processes that are essential to immunity and cancer biology, and identifying new intracellular targets to block bacterial invasion and infectious diseases.
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