Malaria, a disease caused by parasitic protozoans in the genus Plasmodium, is transmitted by mosquitoes to humans. Each year, hundreds of millions of people are infected with this organism and millions of fatalities result, mostly in young children. The problem is how worsening because of the increasing resistance of parasites to drugs. Mosquito control is also threatened because of insecticide resistance, increasing costs, and loss of trained personnel. Thus, new methods for malaria control are needed. An important target for research is the interaction between the mosquito and the parasite. The long-term goal of our research is to understand the molecular determinants of vector competence. We study the ways mosquitoes can kill parasites and how parasites avoid these responses as well as the mosquito factors that malaria parasites require for successful development. With this knowledge, we can attempt to enhance mechanisms that cause mosquito/parasite incompatibilitity through genetic or chemical manipulation of vector mosquitoes or to block the transmission of parasites by targeting mosquito molecules essential for parasite development. The proposed research will focus on how c-type lysozymes affect Plasmodium development in Anopheles gambiae. Silencing of the lysozyme c-1 gene results in a dramatic reduction in the number of mosquitoes that become infected with Plasmodium. Unexpectedly, Lys c-1 binds to oocysts, so this protein directly interacts with parasites.
Specific Aim 1 will focus on 1) describing how Lys c-1 interacts with midgut and salivary stages of malaria parasites, using immunohistqchemical techniques; 2) determining whether anti Lys c-1 antibodies can be used to block parasite development; and 3) characterizing the contribution of Lys c-1 to antibacterial immunity, through gene silencing and subsequent infection with bacteria. Two other lysozymes, Lys c-2 and Lys c-7, are upregulated in the mosquito midgut when parasite infection occurs.
Specific Aim 2 will examine 1) the effect of gene knockdown of Lys c-2 or c-7 on parasite development; and, 2) describing the changes in proteins and transcripts that occur during parasite infections, through western blotting, immunohistochemistry, and quantitative PCR. ? ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
2R01AI037083-09A2
Application #
7142980
Study Section
Special Emphasis Panel (ZRG1-VB-P (01))
Program Officer
Costero, Adriana
Project Start
1995-09-30
Project End
2011-06-30
Budget Start
2006-07-01
Budget End
2007-06-30
Support Year
9
Fiscal Year
2006
Total Cost
$257,250
Indirect Cost
Name
University of Wisconsin Madison
Department
Zoology
Type
Schools of Earth Sciences/Natur
DUNS #
161202122
City
Madison
State
WI
Country
United States
Zip Code
53715
Lapcharoen, Parichat; Komalamisra, Narumon; Rongsriyam, Yupha et al. (2012) Investigations on the role of a lysozyme from the malaria vector Anopheles dirus during malaria parasite development. Dev Comp Immunol 36:104-11
Kajla, Mayur K; Shi, Lei; Li, Bin et al. (2011) A new role for an old antimicrobial: lysozyme c-1 can function to protect malaria parasites in Anopheles mosquitoes. PLoS One 6:e19649
Kajla, Mayur K; Andreeva, Olga; Gilbreath 3rd, Thomas M et al. (2010) Characterization of expression, activity and role in antibacterial immunity of Anopheles gambiae lysozyme c-1. Comp Biochem Physiol B Biochem Mol Biol 155:201-9
Paskewitz, Susan M; Andreev, Olga (2008) Silencing the genes for dopa decarboxylase or dopachrome conversion enzyme reduces melanization of foreign targets in Anopheles gambiae. Comp Biochem Physiol B Biochem Mol Biol 150:403-8
Paskewitz, S M; Li, B; Kajla, M K (2008) Cloning and molecular characterization of two invertebrate-type lysozymes from Anopheles gambiae. Insect Mol Biol 17:217-25
Shi, L; Li, B; Paskewitz, S M (2006) Cloning and characterization of a putative inhibitor of melanization from Anopheles gambiae. Insect Mol Biol 15:313-20
Li, Bin; Paskewitz, Susan M (2006) A role for lysozyme in melanization of Sephadex beads in Anopheles gambiae. J Insect Physiol 52:936-42
Li, Bin; Huang, Yu; Paskewitz, Susan M (2006) Hen egg white lysozyme as an inhibitor of mushroom tyrosinase. FEBS Lett 580:1877-82
Paskewitz, Susan M; Shi, Lei (2005) Bypassing the midgut results in development of Plasmodium berghei oocysts in a refractory strain of Anopheles gambiae (Diptera: Culicidae). J Med Entomol 42:712-5
Paskewitz, Susan M; Shi, Lei (2005) The hemolymph proteome of Anopheles gambiae. Insect Biochem Mol Biol 35:815-24

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