Insect-borne diseases such as malaria continue to devastate a large fraction of the world's population. Transposable element-based transgenic technology has been proposed as a means by which insect vector-borne diseases might be controlled. Indeed, this idea has stimulated an enormous amount of research in the area of mosquito molecular genetics and transposable element biology leading to the development of functional germline transformation vectors and the creation of mosquitoes with genetically engineered refractory phenotypes. Progress has been such that questions of when, where and how this technology can be brought out of the laboratory and applied to problems such as Anopheles gambiae-transmitted malaria in Africa are being considered. The behavior and characteristics of actively transposing insect gene vectors in Anopheles gambiae populations remains a significant unknown. The long range goals of this project (""""""""hobo -like elements in insects"""""""") remain to i) understand the basic biochemistry, genetics and evolution of transposable element movement and regulation, ii) develop transposable elements into gene vectors for nondrosophilid insects, and iii) deploy this technology against human disease vectors. Previous work on this project has contributed to progress toward achieving long-range goals 1 and 2. Current research will focus on a functional and active hobo -like element (Herves) in Anopheles gambiae. This element provides unprecedented opportunities to develop effective mosquito gene vectors and genetic drive agents as well as investigating the behavior of active transposable elements in populations of this important malaria vector.
Our specific aims are to 1) determine the distribution and structure of Herves in An. gambiae and related species, 2) determine the characteristics of Herves movement within An. gambiae populations, 3) develop Herves into a mosquito gene vector.
These aims will be accomplished by performing a combination of laboratory and field-based studies using molecular and population genetics tools.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
2R01GM048102-12A1
Application #
6924820
Study Section
Special Emphasis Panel (ZRG1-VB (01))
Program Officer
Rhoades, Marcus M
Project Start
1992-09-01
Project End
2009-03-31
Budget Start
2005-04-01
Budget End
2006-03-31
Support Year
12
Fiscal Year
2005
Total Cost
$367,513
Indirect Cost
Name
University of MD Biotechnology Institute
Department
Type
Organized Research Units
DUNS #
603819210
City
Baltimore
State
MD
Country
United States
Zip Code
21202
Kim, Yu Jung; Hice, Robert H; O'Brochta, David A et al. (2011) DNA sequence requirements for hobo transposable element transposition in Drosophila melanogaster. Genetica 139:985-97
Arensburger, Peter; Hice, Robert H; Zhou, Liqin et al. (2011) Phylogenetic and functional characterization of the hAT transposon superfamily. Genetics 188:45-57
Subramanian, Ramanand A; Cathcart, Laura A; Krafsur, Elliot S et al. (2009) Hermes transposon distribution and structure in Musca domestica. J Hered 100:473-80
O'Brochta, David A; Stosic, Christina D; Pilitt, Kristina et al. (2009) Transpositionally active episomal hAT elements. BMC Mol Biol 10:108
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
Subramanian, Ramanand A; Arensburger, Peter; Atkinson, Peter W et al. (2007) Transposable element dynamics of the hAT element Herves in the human malaria vector Anopheles gambiae s.s. Genetics 176:2477-87
Sethuraman, Nagaraja; Fraser Jr, Malcolm J; Eggleston, Paul et al. (2007) Post-integration stability of piggyBac in Aedes aegypti. Insect Biochem Mol Biol 37:941-51
Warren, W D; Atkinson, P W; O'Brochta, D A (1994) The Hermes transposable element from the house fly, Musca domestica, is a short inverted repeat-type element of the hobo, Ac, and Tam3 (hAT) element family. Genet Res 64:87-97
O'Brochta, D A; Warren, W D; Saville, K J et al. (1994) Interplasmid transposition of Drosophila hobo elements in non-drosophilid insects. Mol Gen Genet 244:9-14