Mosquito-transmitted parasitic diseases are among the major causes of mortality and morbidity in the world. Recent dramatic increases in the incidence of mosquito-borne diseases, like malaria and dengue fever, and the wide-spread resistance of mosquitoes to insecticides underscores the need for new approaches for insect control based on mosquito-specific agents. The discovery of such mosquito-specific control agents depends on basic research on the biology of mosquitoes. Juvenile hormone (JH) is a major hormonal regulator in insects. In the female mosquito, JH signals the completion of the ecdysis to the adult stage, and initiates reproductive processes. JH titer is essentially determined by the rate at which the corpora allata (CA) synthesizes JH. Our research, using an integrative approach that combines experiments at the organismal, cellular and molecular level, is revealing that mosquito regulation of JH activity has unique features that are related to the adaptation to blood-feeding and the cyclic regulation of ovarian development. We have described that the CA of the female mosquito alternates between periods of high and low biosynthetic activity that are linked to developmental programs and nutritional signals. We have identified neuropeptides that stimulate or inhibit JH synthesis and have characterized their receptors. We have performed the first genomic analysis of an insect endocrine gland and studied the expression of most of the JH biosynthetic enzymes. We have also described that nutrients accumulated during the larval stages regulate CA activity and developed a unique model of nutritionally deficient mosquitoes that do not synthesize JH. The goal of this project is to understand the role and mechanism of action of the different factors that control CA activity (allatoregulatory factors). We also seek to identify the rate limiting steps and regulatory points of JH synthesis. To accomplish these goals, we will focus on two key stages: 1) the activation of JH synthesis in the newly emerged adult female and 2) the inactivation of the CA after blood- feeding. These two stages are critical moments in the reproductive maturation of mosquitoes and make excellent experimental models that are also relevant for disease control. These areas of research should identify targets for designing new, specific and affordable chemical strategies suitable for mosquito control in developing countries.

Public Health Relevance

Mosquito-borne diseases are major public health problems in developing countries. The discovery of mosquito-specific control agents depends on basic research on the biology of mosquitoes. Juvenile hormone (JH) is a major hormonal regulator that controls development and reproduction in mosquitoes and this research aims to understand the unique features of JH synthesis in mosquito and identify targets for designing new, specific and affordable chemical strategies suitable for mosquito depletion or incapacitation in endemic areas.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI045545-12
Application #
8278043
Study Section
Special Emphasis Panel (ZRG1-IDM-A (02))
Program Officer
Costero, Adriana
Project Start
2001-07-01
Project End
2015-05-31
Budget Start
2012-06-01
Budget End
2013-05-31
Support Year
12
Fiscal Year
2012
Total Cost
$438,877
Indirect Cost
$136,203
Name
Florida International University
Department
Biology
Type
Schools of Arts and Sciences
DUNS #
071298814
City
Miami
State
FL
Country
United States
Zip Code
33199
Hernández-Martínez, Salvador; Rivera-Perez, Crisalejandra; Nouzova, Marcela et al. (2015) Coordinated changes in JH biosynthesis and JH hemolymph titers in Aedes aegypti mosquitoes. J Insect Physiol 72:22-7
Nouzova, Marcela; Rivera-Perez, Crisalejandra; Noriega, Fernando G (2015) Allatostatin-C reversibly blocks the transport of citrate out of the mitochondria and inhibits juvenile hormone synthesis in mosquitoes. Insect Biochem Mol Biol 57:20-6
Rivera-Perez, Crisalejandra; Nouzova, Marcela; Lamboglia, Ivanna et al. (2014) Metabolic analysis reveals changes in the mevalonate and juvenile hormone synthesis pathways linked to the mosquito reproductive physiology. Insect Biochem Mol Biol 51:1-9
Areiza, Maria; Nouzova, Marcela; Rivera-Perez, Crisalejandra et al. (2014) Ecdysis triggering hormone ensures proper timing of juvenile hormone biosynthesis in pharate adult mosquitoes. Insect Biochem Mol Biol 54:98-105
Clifton, Mark E; Correa, Stefano; Rivera-Perez, Crisalejandra et al. (2014) Male Aedes aegypti mosquitoes use JH III transferred during copulation to influence previtellogenic ovary physiology and affect the reproductive output of female mosquitoes. J Insect Physiol 64:40-7
Perez-Hedo, Meritxell; Rivera-Perez, Crisalejandra; Noriega, Fernando G (2014) Starvation increases insulin sensitivity and reduces juvenile hormone synthesis in mosquitoes. PLoS One 9:e86183
Rivera-Perez, Crisalejandra; Nouzova, Marcela; Clifton, Mark E et al. (2013) Aldehyde dehydrogenase 3 converts farnesal into farnesoic acid in the corpora allata of mosquitoes. Insect Biochem Mol Biol 43:675-82
Perez-Hedo, Meritxell; Rivera-Perez, Crisalejandra; Noriega, Fernando G (2013) The insulin/TOR signal transduction pathway is involved in the nutritional regulation of juvenile hormone synthesis in Aedes aegypti. Insect Biochem Mol Biol 43:495-500
Nyati, Pratik; Nouzova, Marcela; Rivera-Perez, Crisalejandra et al. (2013) Farnesyl phosphatase, a Corpora allata enzyme involved in juvenile hormone biosynthesis in Aedes aegypti. PLoS One 8:e71967
Mayoral, Jaime G; Leonard, Kate T; Nouzova, Marcela et al. (2013) Functional analysis of a mosquito short-chain dehydrogenase cluster. Arch Insect Biochem Physiol 82:96-115

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