Mosquitoes are well recognized as the most important arthropod vectors of disease-causing pathogens. This is because most species are anautogenous and must feed on the blood of a human or other vertebrate to produce eggs. Multiple cycles of blood feeding and egg development in turn favors frequent contacts with hosts, which makes mosquitoes ideal vectors for pathogen transmission. Since disruption of egg production also disables pathogen transmission, understanding the reproduction of anautogenous mosquitoes is an important area of study. This application is a renewal request to continue our work on how egg development is regulated. Our current award focuses on Aedes aegypti, which is the primary vector of the pathogens that cause Dengue Fever, Zika Virus syndrome and several other human diseases. Our studies indicate that two neurohormones, ovary ecdysteroidogenic hormone (OEH) and insulin-like peptides (ILPs) function as key regulators of the egg development process. The overall goal of this application is to understand how ILP and OEH signaling are tuned to regulate the different processes required for egg production. The studies we propose are innovative because they will be the first to link receptor binding preferences to the function of different ILP family members and OEH. Proposed Specific Aims are to: 1. Characterize the expression and receptor binding properties of different ILP family members and OEH. 2. Characterize the pre- and post-vitellogenic functions of ILPs and OEH. 3. Identify the factors that link nutrient acquisition after blood feeding to ILP and OEH release. Expected outcomes will enhance understanding of how egg formation is regulated in mosquitoes. Our study will significantly impact the field of vector biology by identifying new potential targets for disrupting female reproduction.

Public Health Relevance

Mosquitoes are the most important arthropod vectors of disease-causing pathogens. Proposed studies will characterize the receptor binding preferences and functions of two types of neurohormones, insulin-like peptides and ovary ecdsysteroidogenic hormone, that regulate female mosquito reproduction. Results will identify new potential targets for disrupting female reproduction for potential use in vector control.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI033108-25
Application #
9953961
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Costero-Saint Denis, Adriana
Project Start
1992-07-01
Project End
2024-05-31
Budget Start
2020-06-01
Budget End
2021-05-31
Support Year
25
Fiscal Year
2020
Total Cost
Indirect Cost
Name
University of Georgia
Department
Zoology
Type
Graduate Schools
DUNS #
004315578
City
Athens
State
GA
Country
United States
Zip Code
30602
Nuss, Andrew B; Brown, Mark R (2018) 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 258:140-148
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
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
Strand, M R; Brown, M R; Vogel, K J (2016) Mosquito Peptide Hormones: Diversity, Production, and Function. Adv In Insect Phys 51:145-188
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
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
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

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