Anopheline mosquitoes are the primary vectors of malaria, one of the deadliest and most costly diseases in human history. Measures to control malaria are becoming less effective as both insecticide- and drug-resistance increases. It is clear that new approaches are urgently needed. A new strategy to control mosquito-borne diseases proposes to introduce so-called effector genes or refractory genes into the mosquito that will render the mosquitoes ineffective vectors for pathogens. Developing the means to drive effector genes in natural populations is an urgent priority. The long term objective of this study is to develop an efficient and safe gene drive mechanism that will enable genetic strategies for the control of mosquito-borne infectious diseases. Recently, Chen and colleagues (2007) reported the creation of a synthetic genetic element called Medea in Drosophila that successfully drove population replacement in laboratory. The Drosophila Medea element consists of two parts, a maternally expressed toxin in the form of artificial microRNAs that suppress Myd88, an essential gene for early embryonic development, and a zygotic antidote in the form of a variant of Myd88 that lacks the microRNA targets thus insensitive to the toxin. Building on our preliminary results, we will test the hypothesis that a synthetic Medea gene drive system can be developed in Anopheles stephensi. We will 1) determine the transcriptome profiles during oogenesis and early embryogenesis in An. stephensi;2) select and test components of An. stephensi Medea;and 3) construct a complete An. stephensi Medea element and test for its maternal-effect selfish characteristics and gene drive ability.

Public Health Relevance

Anopheline mosquitoes are the primary vectors of malaria, which is one of the deadliest and most costly infectious diseases in human history. The long term objective of this study is to develop an efficient and safe gene drive mechanism that will enable genetic strategies for the control of mosquito-borne infectious diseases.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI077680-03
Application #
8272606
Study Section
Special Emphasis Panel (ZRG1-VB-P (02))
Program Officer
Costero, Adriana
Project Start
2010-06-01
Project End
2015-05-31
Budget Start
2012-06-01
Budget End
2013-05-31
Support Year
3
Fiscal Year
2012
Total Cost
$379,417
Indirect Cost
$131,917
Name
Virginia Polytechnic Institute and State University
Department
Biochemistry
Type
Schools of Earth Sciences/Natur
DUNS #
003137015
City
Blacksburg
State
VA
Country
United States
Zip Code
24061
Hu, Wanqi; Tu, Zhijian Jake (2018) Functional analysis of the promoter of an early zygotic gene KLC2 in Aedes aegypti. Parasit Vectors 11:655
Wu, Yang; Hu, Wanqi; Biedler, James K et al. (2018) Pure early zygotic genes in the Asian malaria mosquito Anopheles stephensi. Parasit Vectors 11:652
Jiang, X; Hall, A B; Biedler, J K et al. (2017) Single molecule RNA sequencing uncovers trans-splicing and improves annotations in Anopheles stephensi. Insect Mol Biol 26:298-307
Criscione, Frank; Qi, Yumin; Tu, Zhijian (2016) GUY1 confers complete female lethality and is a strong candidate for a male-determining factor in Anopheles stephensi. Elife 5:
Adelman, Zach N; Tu, Zhijian (2016) Control of Mosquito-Borne Infectious Diseases: Sex and Gene Drive. Trends Parasitol 32:219-229
Jiang, Xiaofang; Biedler, James K; Qi, Yumin et al. (2015) Complete Dosage Compensation in Anopheles stephensi and the Evolution of Sex-Biased Genes in Mosquitoes. Genome Biol Evol 7:1914-24
Hu, W; Criscione, F; Liang, S et al. (2015) MicroRNAs of two medically important mosquito species: Aedes aegypti and Anopheles stephensi. Insect Mol Biol 24:240-52
Biedler, James K; Qi, Yumin; Pledger, David et al. (2014) Maternal germline-specific genes in the Asian malaria mosquito Anopheles stephensi: characterization and application for disease control. G3 (Bethesda) 5:157-66
Hall, Andrew Brantley; Timoshevskiy, Vladimir A; Sharakhova, Maria V et al. (2014) Insights into the preservation of the homomorphic sex-determining chromosome of Aedes aegypti from the discovery of a male-biased gene tightly linked to the M-locus. Genome Biol Evol 6:179-91
Jiang, Xiaofang; Peery, Ashley; Hall, A Brantley et al. (2014) Genome analysis of a major urban malaria vector mosquito, Anopheles stephensi. Genome Biol 15:459

Showing the most recent 10 out of 12 publications