"Functional Genomics of Obligate Symbionts"

Yale University, New Haven CT

Investigators

Abstract

Many insects with a single food source throughout their developmental cycle rely on beneficial microbes for essential nutrients absent in their restricted diet. These microbes represent maternally transmitted associations that have coevolved with their respective hosts for millions of years. The associations are so intimate that the bacteria have undergone massive genome reductions and have lost the ability to survive outside their host. Likewise, hosts become sterile in the absence of these obligate symbionts. Comparative analysis of the genome of these obligate microbes with their pathogenic relatives can provide important information on the mechanisms of genome reduction and on the evolution of different forms of symbiosis. Tsetse flies, the sole vectors of African trypanosomes, rely on one such obligate symbiont, Wigglesworthia glossinidia for nutritional provisioning. The genome sequence of Wigglesworthia has recently been completed and found to be 697,724 bp in size. Genes for the biosynthesis of various vitamin metabolites, apparently essential for host functions, have been retained. While this small genome displays many of the features associated with obligate intracellular organisms, it also bears the hallmarks of parasitic and free living microbes such as the ability to synthesize a cell wall and complete flagellum. This project will identify Wigglesworthia genes whose expressions are regulated by changes in the tsetse host traits including sex, diet and physiology. It will also investigate genes that may be important in the transmission of this symbiont to host intrauterine larva. This information will elucidate the functional significance of the symbiosis. Furthermore, given the pivotal role of Wigglesworthia in tsetse fecundity, the study may also reveal targets that can result in novel tsetse control strategies. For this study, we propose to identify Wigglesworthia genes whose expression is regulated by changes in the tsetse host TMs sex, diet and physiology. Furthermore, we intend to explore the potential associations between tsetse, Wigglesworthia, and the trypanosome parasites, and investigate the functional presence of a complete flagella by the intracellular Wigglesworthia and its possible significance in symbiont transmission to tsetse progeny. From an applied perspective for vector control, genes important in the Wigglesworthia transmission process are excellent target candidates to reduce tsetse viability. Alternatively, these symbiotic organisms, which naturally live in close proximity to trypanosomes, can potentially be used in therapeutic approaches to disrupt parasite transmission. These results have the potential to form the basis for future studies where we will begin to either block symbiont expression or interfere with their functions in vivo in efforts to reduce tsetse populations. The funds requested here will provide education and research training to two female doctorate students and projects for Yale University Epidemiology and Public Health Masters candidates.