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
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.
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
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
SKELETAL MUSCLE: REVERSIBLE TEMEPERATURE-INDUCED UNCOUPLING OF CONTRACTION FROM THE ACTIVATOR Ca2+ AND TUBULAR SYSTEM ROLES IN MUSCLE FUNCTION REGULATION. Skeletal muscles represent the largest organ in the body of vertebrates and are responsible for major functions including maintaining posture and locomotion. Skeletal muscles are also a major source of heat production. The project focuses on temperature-induced effects on the ability of the skeletal muscle to contract in warm blooded animals, ....SKELETAL MUSCLE: REVERSIBLE TEMEPERATURE-INDUCED UNCOUPLING OF CONTRACTION FROM THE ACTIVATOR Ca2+ AND TUBULAR SYSTEM ROLES IN MUSCLE FUNCTION REGULATION. Skeletal muscles represent the largest organ in the body of vertebrates and are responsible for major functions including maintaining posture and locomotion. Skeletal muscles are also a major source of heat production. The project focuses on temperature-induced effects on the ability of the skeletal muscle to contract in warm blooded animals, including marsupials, and on the complex roles played by a cellular structure unique to the muscle fibre, the tubular system, with respect to regulation of muscle function at physiological temperatures. The project will test hypotheses that will have far-reaching implications for muscle physiology, cell biology and evolutionary biology.Read moreRead less
Understanding the molecular mechanism of force generation in the bacterial flagellar motor. The proposed research will advance the knowledge about how the bacterial flagellar motor works, enabling scientists to learn more about nature's blueprint of a nanoscale engine. It will address the fundamental question of how bacterial cells convert electrochemical energy into mechanical energy of rotation. At present, the smallest artificial electric motor is still on a micro-, rather than nanoscale. Nan ....Understanding the molecular mechanism of force generation in the bacterial flagellar motor. The proposed research will advance the knowledge about how the bacterial flagellar motor works, enabling scientists to learn more about nature's blueprint of a nanoscale engine. It will address the fundamental question of how bacterial cells convert electrochemical energy into mechanical energy of rotation. At present, the smallest artificial electric motor is still on a micro-, rather than nanoscale. Nanotechnology would therefore benefit from this work by basing their designs on the principles behind the mechanism of the bacterial motor. This research is also of interest for veterinary science, as motility by flagellar motor is a key virulence factor of common animal pathogens associated with, for example, listeriosis and gastroenteritis.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