Identification and characterization of telomere proteins in Plasmodium falciparum.

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The proposed research concerns the human malaria parasite Plasmodium. Malaria is one of the world's most debilitating infectious diseases and Plasmodium is related to several other major parasites of humans and livestock, so a better understanding of it may help us to understand and control other human and animal diseases as well. The lack of effective vaccines against most of these parasites and the emergence of drug-resistant parasites mean that there is an urgent need for research leading to new treatment strategies for malaria and related diseases. Single-celled parasites can replicate very rapidly inside infected people or animals. One basic function that all rapidly-replicating cells must perform is the maintenance of their telomeres: the ends of the chromosomes that make up the cell's genome. Telomeres become slightly shorter every time a cell divides and will eventually become too short for survival if they are not regularly extended. Cancer cells, for example, usually develop a method for replenishing their telomeres that allows them to replicate endlessly and grow out of control, whereas most normal cells in an adult body cannot do this.The malaria parasite, like any other single-celled organism, replenishes its telomeres every time it divides, giving it an infinite capacity for replication. However, Plasmodium is a rather unusual microbe and we know very little about the machinery that controls its telomeres. Our understanding of telomeres in human cells is quite good, but the machinery that maintains telomeres in malaria parasites does not resemble the machinery in human cells. This project therefore focuses on the maintenance of telomeres in the malaria parasite. A better understanding of this could point us in the direction of new drug targets, since disrupting the structure and maintenance of telomeres is often lethal.To find this machinery will require a biological fishing expedition. The whole genome of the malaria parasite will be broken up into pieces and the telomeric DNA will be fished out along with the proteins bound to it. These will then be identified and the experiment will be followed up by knocking out some of these proteins in parasites grown in the lab, to test whether they actually do control telomeres. Overall, the study will give us a better understanding of the mechanisms that maintain the telomeres of these unusual parasites. It may inform new drug strategies to combat malaria and related parasitic diseases affecting both humans and animals. The outcomes of the research will be published in open-access scientific journals and presented at international conferences. They will be communicated to the general public via lay summaries on appropriate websites and via science-writing in magazines and/or online.