Genetically Modifying Mosquitoes Without Compromising Fitness: Can It Be Done?
AuthorHun, Lewis Vibul
Lifespan and reproduction
Mosquito insulin-like peptides
AdvisorRiehle, Michael A.
MetadataShow full item record
PublisherThe University of Arizona.
RightsCopyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction, presentation (such as public display or performance) of protected items is prohibited except with permission of the author.
AbstractMalaria is a mosquito-borne disease caused by parasites belonging to the genus Plasmodium. Malaria remains one of the most devastating infectious diseases, killing nearly half a million people each year (WHO 2015). 1,2 With the current increase in drug and insecticide resistance, there is an urgent need to develop novel strategies for malaria control. One such strategy to genetically engineer mosquito vectors to make them resistant to infection by malaria parasites in order to replace the wild population with malaria refractory mosquitoes. The insulin/IGF-like signaling (IIS) pathway is one potential target for a population replacement strategy since it regulates metabolism, immunity, lifespan and reproduction in mosquitoes. We previously generated a transgenic Anopheles stephensi line with increased insulin signaling in the fat body. Surprisingly, these transgenic mosquitoes survived significantly longer than their non-transgenic siblings, while in nearly every other organism increased IIS resulted in a decrease in lifespan. In this work, we sought to define how the fat body IIS controls lifespan, and also to determine the impact of the fat body IIS on reproduction, metabolism, and Plasmodium resistance. We found that overexpression of the molecule Akt, a key IIS nexus molecule, resulted in an increased overall fitness and enhanced Plasmodium falciparum parasite resistance in transgenic Anopheles stephensi, as compared to their non-transgenic siblings. Overall results from these studies highlight the important role of IIS in the mosquito fat body in controlling lifespan, reproduction, metabolism and immunity.
Degree ProgramGraduate College
Entomology and Insect Science
Degree GrantorUniversity of Arizona
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Mosquitoes: Biology and Integrated Mosquito ManagementGouge, Dawn H.; Li, Shujuan; Walker, Kathleen; Sumner, Chris; Nair, Shaku; Olson, Carl; Univ Arizona, Coll Agr & Life Sci (College of Agriculture, University of Arizona (Tucson, AZ), 2016-07)Mosquitoes are the most important insect pests that affect the health and well-being of humans and domestic animals worldwide. They can cause a variety of health problems due to their ability to transfer (vector) viruses and other disease-causing pathogens, including in the arid Southwest U.S. This publication describes the mosquito life-cycle, introduces common pest mosquito species and the diseases associated with them. Mosquito management for residents is covered.
Molecular characterization of a blood-meal induced trypsin from the mosquito Aedes aegypti.Barillas Mury, Carolina Veronica. (The University of Arizona., 1992)Adult and laIval midgut trypsins from the mosquito Aedes aegypli were isolated using benzamidine affinity chromatography. The cDNA of the late trypsin induced by the blood meal was isolated using an anti-trypsin monoclonal antibody, cloned and sequenced. The 862 bp sequence codes for a 257 amino acid protein, which is presumably a trypsin precursor, since the sequence of purified mosquito trypsin begins at residue 26, immediately following an arginine residue in the precursor. The amino terminal 25 amino acids in the precursor are composed of a putative 15 amino acid signal peptide and a 10 amino acid activation peptide. The activation peptide in the mosquito is different from that of vertebrate trypsinogens and suggests that activation takes place by tryptic cleavage. The deduced amino acid sequence is homologous to that of other trypsins in those residues around the catalytic triad, and in several residues which are found only in trypsins. However, the sequence of the specificity pocket in mosquito trypsin, KESPC, differs from that found in other trypsins, KDSC. The Asp is thought to bind the basic residue of the substrate, and the Glu in the mosquito trypsin may serve the same role. The changes in trypsin protein and mRNA levels following a blood meal indicate that an important component of the regulation of trypsin synthesis is at the transcriptional level. A genomic clone of "late trypsin" was isolated, mapped, and 1.2 kb of the upstream regulatory region were sequenced. The gene has no introns within the coding region. A TAT A box consensus sequence (TAT AAA) was found at position -31 from the 5' end of the mature mRNA. A cluster of five repeat sequences homologous to the GCN4 DNA binding site was found within 200 nucleotides upstream of the cap site. GCN4 is required for derepression mediated control of general amino acid biosynthesis in response to amino acid starvation in yeast. This suggests that a similar protein might regulate expression of the late trypsin gene in the mosquito. Southern blot analysis of genomic DNA suggests that the regions flanking the late trypsin coding region are polymorphic.