Many devastating human diseases are transmitted by mosquitoes because of their requirement to blood feed for egg development. Disease-causing pathogens have adapted successfully to exploit this feature of mosquito biology for their own life cycles. Hence, the understanding of molecular mechanisms controlling egg development in these vectors is essential for devising novel methods to disrupt disease spread. We will thus decipher the hormonal genetic pathways that regulate mosquito female reproduction;the juvenile hormone regulatory cascade governing the post-eclosion development of the Aedes aegypti female fat body (FB;the tissue essential for egg development) will be investigated by means of transcriptome, bioinformatics, and RNA interference analyses. We will also decipher the differential action of the 20-hydroxyecdysone regulatory cascade in controlling genes critical for the progression of vitellogenesis in A. aegypti. We will determine cis motifs responsible for co-regulating specific patterns of FB gene expression. The newly developed mosquito GAL4-UAS genetic system will permit testing these promoters. This genetic system is also invaluable in evaluating functions of genes, identified in transcriptomic screens, by means of their mis-regulation or RNAi-depletion. Accomplishment of the goals of this comprehensive research program will significantly advance our understanding of the molecular basis of mosquito reproduction, and the resulting data will build a foundation for deciphering new targets for mosquito control.

Public Health Relevance

Mosquitoes transmit many devastating human diseases because of their requirement to blood feed for egg development. Disease-causing pathogens have successfully adapted to exploit this feature of mosquito biology. The understanding of molecular mechanisms controlling egg development is thus essential for devising novel methods to disrupt disease spread. In this research project, we will elucidate hormonal genetic pathways regulating mosquito female reproduction, the knowledge of which will build a foundation for deciphering new targets for mosquito control.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI036959-19
Application #
8619575
Study Section
Special Emphasis Panel (ZRG1-IDM-V (02))
Program Officer
Costero, Adriana
Project Start
1995-07-01
Project End
2017-02-28
Budget Start
2014-03-01
Budget End
2015-02-28
Support Year
19
Fiscal Year
2014
Total Cost
$504,315
Indirect Cost
$168,717
Name
University of California Riverside
Department
Zoology
Type
Schools of Earth Sciences/Natur
DUNS #
627797426
City
Riverside
State
CA
Country
United States
Zip Code
92521
Ling, Lin; Kokoza, Vladimir A; Zhang, Changyu et al. (2017) MicroRNA-277 targets insulin-like peptides 7 and 8 to control lipid metabolism and reproduction in Aedes aegypti mosquitoes. Proc Natl Acad Sci U S A 114:E8017-E8024
Wang, Y; Jiang, H; Cheng, Y et al. (2017) Activation of Aedes aegypti prophenoloxidase-3 and its role in the immune response against entomopathogenic fungi. Insect Mol Biol 26:552-563
Wang, Xueli; Hou, Yuan; Saha, Tusar T et al. (2017) Hormone and receptor interplay in the regulation of mosquito lipid metabolism. Proc Natl Acad Sci U S A 114:E2709-E2718
Wang, Jia-Lin; Saha, Tusar T; Zhang, Yang et al. (2017) Juvenile hormone and its receptor methoprene-tolerant promote ribosomal biogenesis and vitellogenesis in the Aedes aegypti mosquito. J Biol Chem 292:10306-10315
Saha, Tusar T; Shin, Sang Woon; Dou, Wei et al. (2016) Hairy and Groucho mediate the action of juvenile hormone receptor Methoprene-tolerant in gene repression. Proc Natl Acad Sci U S A 113:E735-43
H Backman, Tyler W; Girke, Thomas (2016) systemPipeR: NGS workflow and report generation environment. BMC Bioinformatics 17:388
Zhao, Bo; Hou, Yuan; Wang, Jianjun et al. (2016) Determination of juvenile hormone titers by means of LC-MS/MS/MS and a juvenile hormone-responsive Gal4/UAS system in Aedes aegypti mosquitoes. Insect Biochem Mol Biol 77:69-77
Wang, Yan-Hong; Hu, Yang; Xing, Long-Sheng et al. (2015) A Critical Role for CLSP2 in the Modulation of Antifungal Immune Response in Mosquitoes. PLoS Pathog 11:e1004931
Hou, Yuan; Wang, Xue-Li; Saha, Tusar T et al. (2015) Temporal Coordination of Carbohydrate Metabolism during Mosquito Reproduction. PLoS Genet 11:e1005309
Lucas, Keira J; Zhao, Bo; Roy, Sourav et al. (2015) Mosquito-specific microRNA-1890 targets the juvenile hormone-regulated serine protease JHA15 in the female mosquito gut. RNA Biol 12:1383-90

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