Use Of Novel Transfection Protocols To Study Protein Trafficking In Malaria-infected Erythrocytes
Funder
National Health and Medical Research Council
Funding Amount
$211,527.00
Summary
Malaria kills between 1 and 3 million children each year. In addition, the disease debilitates the adult population in malaria-endemic areas, thereby contributing to the cycle of poverty in many third world countries. As resistance to existing antimalarial drugs increases, there is an urgent need to understand the workings of the parasite at a molecular level to enable the development of alternative antimalarial strategies. During part of its life cycle, the malaria parasite infects the erythroc ....Malaria kills between 1 and 3 million children each year. In addition, the disease debilitates the adult population in malaria-endemic areas, thereby contributing to the cycle of poverty in many third world countries. As resistance to existing antimalarial drugs increases, there is an urgent need to understand the workings of the parasite at a molecular level to enable the development of alternative antimalarial strategies. During part of its life cycle, the malaria parasite infects the erythrocytes of its human host. The parasite transports proteins to the erythrocyte membrane so as to modify the properties of its adopted cellular residence. The parasite proteins that are deposited at or in the erythrocyte membrane increase the leakiness and the stickiness of the parasitised erythrocytes. This allows more efficient uptake of nutrients and allows the parasitised erythrocytes to adhere to blood vessel walls, thereby avoiding passage through the spleen. Adherence of parasitised erythrocytes to capillaries in the brain is thought to lead to the development of the complication known as cerebral malaria. This complication is responsible for most of the deaths due to malaria. In order to traffic the adherence proteins to the erythrocyte surface, the parasite establishes a novel transport pathway for moving proteins across the erythrocyte cytoplasm. As the uninfected erythrocyte has no means, nor requirement, for moving proteins, this novel transport mechanism may represent a target for drugs that kill the malaria parasite without being toxic to humans. The pathways for the movement of proteins around the infected erythrocyte are largely unknown. We propose to use techniques to introduce foreign genes into malaria-infected erythrocytes to unravel the details of the molecular machinery and the ticketing system that the parasite uses to traffic proteins to their correct destinations in its adopted home.Read moreRead less
Protein Trafficking In Malaria Parasite-infected Erythrocytes
Funder
National Health and Medical Research Council
Funding Amount
$417,750.00
Summary
Malaria kills between 1 and 3 million children each year. In addition, the disease debilitates the adult population in malaria-endemic areas, thereby contributing to the cycle of poverty in many third world countries. As resistance to existing antimalarial drugs increases, there is an urgent need to understand the workings of the parasite at a molecular level to enable the development of alternative antimalarial strategies. During part of its life cycle, the malaria parasite infects the erythroc ....Malaria kills between 1 and 3 million children each year. In addition, the disease debilitates the adult population in malaria-endemic areas, thereby contributing to the cycle of poverty in many third world countries. As resistance to existing antimalarial drugs increases, there is an urgent need to understand the workings of the parasite at a molecular level to enable the development of alternative antimalarial strategies. During part of its life cycle, the malaria parasite infects the erythrocytes of its human host. The parasite transports proteins to the erythrocyte membrane so as to modify the properties of its adopted cellular residence. The parasite proteins that are deposited at or in the erythrocyte membrane increase the leakiness and the stickiness of the parasitised erythrocytes. This allows more efficient uptake of nutrients and allows the parasitised erythrocytes to adhere to blood vessel walls, thereby avoiding passage through the spleen. Adherence of parasitised erythrocytes to capillaries in the brain is thought to lead to the development of the complication known as cerebral malaria. This complication is responsible for most of the deaths due to malaria. In order to traffic the adherence proteins to the erythrocyte surface, the parasite establishes novel transport pathways for moving proteins across the erythrocyte cytoplasm. As the uninfected erythrocyte has no means, nor requirement, for moving proteins, this novel transport mechanism may represent a target for drugs that kill the malaria parasite without being toxic to humans. The pathways for the movement of proteins around the infected erythrocyte are largely unknown. We propose to use cell biology techniques and techniques to introduce foreign genes into malaria-infected erythrocytes to unravel the details of the molecular machinery and the ticketing system that the parasite uses to traffic proteins to their correct destinations in its adopted home.Read moreRead less
Regulation Of Nuclear Import Of Viral Oncoproteins And Transcription Factors By Protein-protein Interactions
Funder
National Health and Medical Research Council
Funding Amount
$650,383.00
Summary
The present application examines the controls that exerted over proteins that localize in the nucleus of eukaryotic cells. This relates relates integrally to cellular processes such as growth, development and oncogenesis. This research area is not represented elsewhere in Australia, and the particular experimental strategies to approach the problem, revolving around the use of special quantitative microscopic techniques are novel internationally. One part of the application seeks to examine tran ....The present application examines the controls that exerted over proteins that localize in the nucleus of eukaryotic cells. This relates relates integrally to cellular processes such as growth, development and oncogenesis. This research area is not represented elsewhere in Australia, and the particular experimental strategies to approach the problem, revolving around the use of special quantitative microscopic techniques are novel internationally. One part of the application seeks to examine transport within the cell of complexes of interacting proteins, rather than single proteins, under as close as possible to physiologically relevant conditions. This will be truly unique, and of great importance to our comprehension of eukaryotic cell function. This application examines particular types of negative control over protein nuclear localization. Since many proteins show such regulation, and in particular important proteins controlling cell growth and division, the results are fundamentally important to our understanding of how cells function in general. Further, this understanding may be applied in disease situations, such as viral-mediated oncogenesis. In the work we propose to do, viral proteins with functions relating to cancer will be examined in detail, as well as a cellular protein which is recognised by them - the tumor suppressor Rb. We intend to examine several viral oncoproteins which target Rb; one is a protein (E7) from the Human Papilloma Virus which has been frequently associated with cervical carcinomas and other cancers. Accordingly, the results may have direct application to viral-induced cancer, and our work may lead to understanding of the regulation of protein transport to the nucleus. This may thus afford a new approach at the pharmacological level to combat transformation.Read moreRead less