Mosquito-borne diseases represent major health problems in most developing countries and have emerged as significant threats for epidemic outbreaks in developed countries. Exacerbating these problems are the emergence of insecticide resistance in mosquito populations, drug resistance among parasite populations, delayed progress in vaccine development, lack of support for mosquito control programs, and increased global travel. Mosquitoes in the Culex pipiens complex are primary vectors for the lymphatic filarioid nematode parasite, Wuchereria bancrofti and several arboviruses. This includes the recently introduced West Nile virus in North America. The long- term objectives of the proposed research are to identify, isolate and characterize genetic factors associated with diapause, a trait that strongly impacts the geographic distribution and survival of species within the Culex pipiens complex. At present, no knowledge exists on the molecular determinants of diapause in Culex. The objectives of this proposal are based on the general hypothesis that genes associated with the diapause phenotype can be identified and isolated by positional cloning techniques. Identification of genes determining diapause and the knowledge from the detailed understanding of the associated biochemical pathways could have several potential applications including: transgene constructs that promote altered and disease limiting behaviors following population replacement, development of targeted biopesticides, or identification of biologically relevant antagonists that disrupt behaviors critical to pathogen transmission or survival.
The specific aims of the project are to: 1) fine-scale map genome regions identified as containing genes that determine the diapause phenotype, 2) identify candidate genes determining diapause, and 3) conduct functional analysis of candidate genes determining diapause. Information from genetic crosses will be leveraged against the Cx. quinquefasciatus genome project to identify candidate genes within discrete genome regions. Candidate genes will be evaluated using microarrays, followed by quantitative real time PCR assays to confirm and expand microarray results for promising genes. Positive candidate genes will be assayed for biological relevance using RNA interference mediated gene knockdowns or gene overexpression using recombinant Sindbis transducing viruses. Results from laboratory experiments will then be evaluated among natural populations representing Cx. pipiens s.s. and Cx. quinquefasciatus.

Public Health Relevance

Mosquitoes in the Culex pipiens complex are primary vectors for human lymphatic filariasis and several arboviruses, including the West Nile virus. No vaccines are available and disease prevention is largely dependent on avoiding contact with infected mosquitoes. The proposed research will provide valuable new information on the biology of the mosquito relating to the ability of adult females to survive temperate climate winter in a diapause state.

National Institute of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
Research Project (R01)
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Special Emphasis Panel (ZRG1-IDM-M (02))
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Costero, Adriana
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University of Notre Dame
Schools of Arts and Sciences
Notre Dame
United States
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Behura, Susanta K; Severson, David W (2015) Bidirectional promoters of insects: genome-wide comparison, evolutionary implication and influence on gene expression. J Mol Biol 427:521-36
Behura, Susanta K; Severson, David W (2013) Overlapping genes of Aedes aegypti: evolutionary implications from comparison with orthologs of Anopheles gambiae and other insects. BMC Evol Biol 13:124
Hickner, Paul V; Mori, Akio; Chadee, Dave D et al. (2013) Composite linkage map and enhanced genome map for Culex pipiens complex mosquitoes. J Hered 104:649-55
Behura, Susanta K; Severson, David W (2013) Codon usage bias: causative factors, quantification methods and genome-wide patterns: with emphasis on insect genomes. Biol Rev Camb Philos Soc 88:49-61
Severson, David W; Behura, Susanta K (2012) Mosquito genomics: progress and challenges. Annu Rev Entomol 57:143-66
Behura, Susanta K; Lobo, Neil F; Haas, Brian et al. (2011) Complete sequences of mitochondria genomes of Aedes aegypti and Culex quinquefasciatus and comparative analysis of mitochondrial DNA fragments inserted in the nuclear genomes. Insect Biochem Mol Biol 41:770-7
Behura, Susanta K; Haugen, Morgan; Flannery, Ellen et al. (2011) Comparative genomic analysis of Drosophila melanogaster and vector mosquito developmental genes. PLoS One 6:e21504
Hickner, Paul V; Debruyn, Becky; Lovin, Diane D et al. (2010) Genome-based microsatellite development in the Culex pipiens complex and comparative microsatellite frequency with Aedes aegypti and Anopheles gambiae. PLoS One 5: