Ecdysteroid hormones are key regulators of development and reproduction in the mosquitoes, Aedes aegypti and Anopheles gambiae. The proposed research will focus on the molecular characterization and expression of two types of peptide hormones involved in the activation of ecdysteroid hormone production in females of these species. First, the secretion of ovary ecdysteroidogenic hormone (OEM) and insulin-like peptides (ILPs) will be characterized. Second, their receptors and signalling pathways will be delineated. Third, activation of ecdysteroid biosynthesis by peptide hormones provides an experimental approach to identify .new proteins and their genes specifically involved in this essential process, which is incompletely known for insects. Indeed, the mosquito ovary is an exceptionally robust model for such discoveries. Peptide-treated and control ovaries will be compared by proteomic analysis to reveal translational and post- translational changes in particular proteins that then will be identified in genome databases. In addition, suppressive subtractive hybridization of cDNAs from experimental ovaries will be used to obtain a cDNA library that will be examined for novel and known gene products transcribed in response to peptide hormone activation of ecdysteroid biosynthesis. Candidate genes and proteins then will be subjected to quantitative PCR and immunoassays, and to RNA interference knockdown in vivo and in bioassays to substantiate the observed changes. The proposed work has practical import for public health in that the identification of mosquito-specific enzymes involved in ecdysteroid biosynthesis may provide targets for novel substrate poisons. As well, knowledge of peptide hormones and their receptors may allow design of bioactive, stable peptide mimics that disrupt key regulatory processes. Such chemicals may lead to the development of new pesticides that provide cost-effective and strategic reductions in mosquito populations and lessen their nuisance and ability to transmit pathogens.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI033108-17
Application #
7740140
Study Section
Vector Biology Study Section (VB)
Program Officer
Costero, Adriana
Project Start
1992-07-01
Project End
2011-12-31
Budget Start
2010-01-01
Budget End
2010-12-31
Support Year
17
Fiscal Year
2010
Total Cost
$268,048
Indirect Cost
Name
University of Georgia
Department
Zoology
Type
Schools of Arts and Sciences
DUNS #
004315578
City
Athens
State
GA
Country
United States
Zip Code
30602
McKinney, David A; Strand, Michael R; Brown, Mark R (2017) Evaluation of ecdysteroid antisera for a competitive enzyme immunoassay and extraction procedures for the measurement of mosquito ecdysteroids. Gen Comp Endocrinol 253:60-69
Nuss, Andrew B; Brown, Mark R (2017) Isolation of an insulin-like peptide from the Asian malaria mosquito, Anopheles stephensi, that acts as a steroidogenic gonadotropin across diverse mosquito taxa. Gen Comp Endocrinol :
McKinney, David A; Eum, Jai-Hoon; Dhara, Animesh et al. (2016) Calcium influx enhances neuropeptide activation of ecdysteroid hormone production by mosquito ovaries. Insect Biochem Mol Biol 70:160-9
Gulia-Nuss, Monika; Elliot, Anne; Brown, Mark R et al. (2015) Multiple factors contribute to anautogenous reproduction by the mosquito Aedes aegypti. J Insect Physiol 82:8-16
Vogel, Kevin J; Brown, Mark R; Strand, Michael R (2015) Ovary ecdysteroidogenic hormone requires a receptor tyrosine kinase to activate egg formation in the mosquito Aedes aegypti. Proc Natl Acad Sci U S A 112:5057-62
Coon, Kerri L; Vogel, Kevin J; Brown, Mark R et al. (2014) Mosquitoes rely on their gut microbiota for development. Mol Ecol 23:2727-39
Hillyer, Julián F; Strand, Michael R (2014) Mosquito hemocyte-mediated immune responses. Curr Opin Insect Sci 3:14-21
Vogel, Kevin J; Brown, Mark R; Strand, Michael R (2013) Phylogenetic investigation of Peptide hormone and growth factor receptors in five dipteran genomes. Front Endocrinol (Lausanne) 4:193
Dhara, Animesh; Eum, Jai-Hoon; Robertson, Anne et al. (2013) Ovary ecdysteroidogenic hormone functions independently of the insulin receptor in the yellow fever mosquito, Aedes aegypti. Insect Biochem Mol Biol 43:1100-8
Kaufmann, Christian; Collins, Lauren F; Brown, Mark R (2013) Influence of Age and Nutritional Status on Flight Performance of the Asian Tiger Mosquito Aedes albopictus (Diptera: Culicidae). Insects 4:

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