Oxidative stress-induced alterations of the host erythrocyte by the malaria parasite. The malaria parasite spends part of its lifecycle inside the red blood cells of its host. During this time, the parasite modifies many of the features of the red blood cell and subjects it to high levels of oxidative stress. We will use and develop a variety of fluorescence and microscopic techniques to understand the molecular basis of the alterations in the organization of membrane proteins in malaria parasit ....Oxidative stress-induced alterations of the host erythrocyte by the malaria parasite. The malaria parasite spends part of its lifecycle inside the red blood cells of its host. During this time, the parasite modifies many of the features of the red blood cell and subjects it to high levels of oxidative stress. We will use and develop a variety of fluorescence and microscopic techniques to understand the molecular basis of the alterations in the organization of membrane proteins in malaria parasite-infected red blood cells. We will examine the roles of oxidative stress and of parasite proteins in modulating the properties of the host cell membrane.Read moreRead less
The functional organisation of the trans-Golgi network: From cultured cells to physiological systems. This research will result in a better understanding of the secretory pathway of all eukaryotic cells, a process of broad biological and biomedical significance. It will impact on cell biology in the broadest sense, from membrane biogenesis to lipid domain organization, as well as membrane transport, protein structure and protein targeting. Furthermore, this work will utilize and develop fronti ....The functional organisation of the trans-Golgi network: From cultured cells to physiological systems. This research will result in a better understanding of the secretory pathway of all eukaryotic cells, a process of broad biological and biomedical significance. It will impact on cell biology in the broadest sense, from membrane biogenesis to lipid domain organization, as well as membrane transport, protein structure and protein targeting. Furthermore, this work will utilize and develop frontier technologies of live cell imaging and RNA interference as a genetic tool to investigate functions of a protein family. By training post-graduate students and post-doctoral staff, it will contribute to the expertise of cell biology in Australia. International collaborations will enhance connections between Australia and overseas research.Read moreRead less
The structure and function of the trans-Golgi network: role of golgins and G proteins. This research will provide a better understanding of the secretory pathway of all eukaryotic cells, a process of broad biological and biomedical significance. It will also contribute to a better understanding of how a cell works, including how cell membranes are organization, how the transport processes of the cell are regulated and how proteins are targeted to their intracellular destination. Further, this ....The structure and function of the trans-Golgi network: role of golgins and G proteins. This research will provide a better understanding of the secretory pathway of all eukaryotic cells, a process of broad biological and biomedical significance. It will also contribute to a better understanding of how a cell works, including how cell membranes are organization, how the transport processes of the cell are regulated and how proteins are targeted to their intracellular destination. Further, this work will utilize the frontier technology of RNA interference as a genetic tool to investigate functions of genes. By training post-graduate students and post-doctoral staff, it will contribute to the expertise of cell biology in Australia. International collaborations will enhance connections with overseas researchers.Read moreRead less
The role of a novel family of Golgi proteins in maintaining the structure and function of the trans-Golgi network. The secretory pathway of eukaryotic cells is fundamental for proper cell growth. The Golgi apparatus is a key organelle of this pathway where newly made proteins are selectively packaged into membrane-bound transport vehicles and then shipped to their correct destination, such as the surface of the cell. This research aims to understand the mechanism by which these cargo-loaded tr ....The role of a novel family of Golgi proteins in maintaining the structure and function of the trans-Golgi network. The secretory pathway of eukaryotic cells is fundamental for proper cell growth. The Golgi apparatus is a key organelle of this pathway where newly made proteins are selectively packaged into membrane-bound transport vehicles and then shipped to their correct destination, such as the surface of the cell. This research aims to understand the mechanism by which these cargo-loaded transport vehicles are generated from the Golgi apparatus. This information is of fundamental importance in understanding how a cell survives and grows, and is necessary to allow a rational basis for the engineering of secreted recombinant molecules.Read moreRead less
Tail-anchored membrane proteins: prediction, targeting, assembly and function. Using computer-based searches of genome sequence data, we now have a complete list of tail-anchored membrane proteins in the yeast Saccharomyces cerevisiae. These include a number of essential proteins, such as SNAREs and TOM proteins responsible for building cellular membranes in all organisms, including man. Of the additional protein sequences discovered in the search, 8 represent proteins of known function while 19 ....Tail-anchored membrane proteins: prediction, targeting, assembly and function. Using computer-based searches of genome sequence data, we now have a complete list of tail-anchored membrane proteins in the yeast Saccharomyces cerevisiae. These include a number of essential proteins, such as SNAREs and TOM proteins responsible for building cellular membranes in all organisms, including man. Of the additional protein sequences discovered in the search, 8 represent proteins of known function while 19 are novel. We propose to study the subcellular location of these 19 novel proteins, and solve how they are targeted to and inserted in membranes. We will also investigate the function of the newly-discovered proteins.Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE150101777
Funder
Australian Research Council
Funding Amount
$375,000.00
Summary
Understanding the role of exosomes in intercellular communication. Exosomes, small packages released by cells, are powerful signalling organelles that can activate neighbouring cells by transferring proteins and RNA. Currently, it is unknown whether exosomes have similar membrane protein/lipid composition to that of the host cell. This project aims to explore the similarities and differences between the exosomal and host cell membranes in terms of the protein/lipid composition. In addition, the ....Understanding the role of exosomes in intercellular communication. Exosomes, small packages released by cells, are powerful signalling organelles that can activate neighbouring cells by transferring proteins and RNA. Currently, it is unknown whether exosomes have similar membrane protein/lipid composition to that of the host cell. This project aims to explore the similarities and differences between the exosomal and host cell membranes in terms of the protein/lipid composition. In addition, the project aims to study how the proteins and RNA are packaged into exosomes. Membrane molecules that are detected only in the exosomes may have important signalling implications and may aid in the uptake/fusion of exosomes by/with target cells. The project aims to improve our understanding on signalling mediated by exosomes.Read moreRead less
Membrane Attack Complex / Perforin like proteins in Defence, Attack and Developmental Biology. This proposal will result in a major advancement of knowledge, for example, in our understanding of the emerging links between immunity and development as well as the role and mechanism of function of the pore forming family of MACPF proteins in host defence, attack, embryo development and diseases such as cancer. These data will be crucial for developing approaches to control unwanted MACPF function, ....Membrane Attack Complex / Perforin like proteins in Defence, Attack and Developmental Biology. This proposal will result in a major advancement of knowledge, for example, in our understanding of the emerging links between immunity and development as well as the role and mechanism of function of the pore forming family of MACPF proteins in host defence, attack, embryo development and diseases such as cancer. These data will be crucial for developing approaches to control unwanted MACPF function, for example in disease such as diabetes or transplant rejection. Furthermore, a detailed understanding of how MACPF proteins assemble into rings and punch holes in membranes will facilitate the development of these proteins as technological tools.Read moreRead less
Delineating the role of the GxxxG motif in transmembrane protein metabolism. This study will define how a well defined motif involved in transmembrane interactions affects the metabolism of proteins. Since this motif is present in proteins involved in Alzheimer's disease it has potential benefits for community health and combating ageing.
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
Structure, dynamics and interactions of Plasmodium falciparum merozoite surface protein-2. The solution structure of the merozoite surface protein-2 (MSP-2), from Plasmodium falciparum the causative agent of malaria, will be determined along with an analysis of the motions of residues within the protein. This will allow insights into interactions occurring at the surface coat of the organism, where MSP-2 is a major component. An understanding of how this protein interacts with antibodies of the ....Structure, dynamics and interactions of Plasmodium falciparum merozoite surface protein-2. The solution structure of the merozoite surface protein-2 (MSP-2), from Plasmodium falciparum the causative agent of malaria, will be determined along with an analysis of the motions of residues within the protein. This will allow insights into interactions occurring at the surface coat of the organism, where MSP-2 is a major component. An understanding of how this protein interacts with antibodies of the host's immune system will also be gained. The techniques established during the study of MSP-2 will be useful for the study of larger proteins and protein complexes from many systems in the future.Read moreRead less