Insect-born diseases such as malaria can be controlled in a variety of ways ranging from the treatment of sick patients to eliminating the insects that transmit the pathogens or parasites. The work described here will advance efforts to evaluate the feasibility of applying certain insect biotechnological approaches to the control of malaria transmission. Insect genetics-based strategies for controlling diseases such as malaria in Africa are being developed with some success in the laboratory. Using transgenic insect technologies Anopheles mosquitoes have been created that express a variety of effector-genes that reduce or eliminate the capacity of these insects to support Plasmodium development. While the insects produced to date have not had optimal phenotypes they have served to demonstrate that Plasmodium development and transmission in Anopheles mosquitoes can be disrupted using existing insect genetic engineering technologies. However, in order for effective laboratory-created genotypes to be of any practical use in controlling malaria transmission in natural environments they will have to be introduced into and spread through natural populations of the target species. Technologies for accomplishing this objective have yet to be identified although a number of candidates exist. Class II transposable elements have been suggested as gene spreading agents based on their natural history. Whether any of the existing insect gene vectors could serve to spread anti-Plasmodium transgenes through populations of Anopheles gambiae remains untested. This major deficiency in the efforts to explore the feasibility of the idea of manipulating vector competence for the purposes of disease transmission control will be addressed in the work proposed here. Following the introduction of conditionally autonomous Hermes, Minos, Mos1 and piggyBac elements into An. gambiae their remobilization, replication and spreading potential will be quantitatively assessed.
The specific aims are to 1) assess the remobilization potential of Hermes, Minos, Mos1 and piggyBac in An. gambiae, 2) determine the patterns of remobilization of Hermes, Minos, Mos1 and piggyBac in An. gambiae, 3) assess the replicative potential of Hermes, Minos, Mos1 and piggyBac in An. gambiae, 4) assess the spreading potential of Hermes, Minos, Mos1 and piggyBac in An. gambiae. At the end of this project the relative promise of each of these transposable elements to contribute to the development of population replacement technology for An. gambiae will be known. This project involves the use of Animals but does not involve Human Subjects.
| Palavesam, Azhahianambi; Esnault, Caroline; O'Brochta, David A (2013) Post-integration silencing of piggyBac transposable elements in Aedes aegypti. PLoS One 8:e68454 |
| O'Brochta, David A; Pilitt, Kristina L; Harrell 2nd, Robert A et al. (2012) Gal4-based enhancer-trapping in the malaria mosquito Anopheles stephensi. G3 (Bethesda) 2:1305-15 |
| Esnault, Caroline; Palavesam, Azhahianambi; Pilitt, Kristina et al. (2011) Intrinsic characteristics of neighboring DNA modulate transposable element activity in Drosophila melanogaster. Genetics 187:319-31 |
| O'Brochta, David A; Alford, Robert T; Pilitt, Kristina L et al. (2011) piggyBac transposon remobilization and enhancer detection in Anopheles mosquitoes. Proc Natl Acad Sci U S A 108:16339-44 |
| Subramanian, Ramanand A; Akala, Olabiyi O; Adejinmi, Johnson O et al. (2008) Topi, an IS630/Tc1/mariner-type transposable element in the African malaria mosquito, Anopheles gambiae. Gene 423:63-71 |
