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 2-3 million fatalities result, mostly in young children. The problem is most severe in Africa, and is now worsening because of the increasing resistance of parasites to the inexpensive drugs used for prevention and control in the past. A second important strategy for control, reducing mosquito populations through insecticide use, is also threatened because of insecticide resistance, increasing costs and loss of trained personnel. A new target for research has been the interaction between the mosquito and the parasite. The long-term goal of the research presented here is to understand the molecular basis for incompatibility between mosquitoes and malaria parasites because this may suggest ways to enhance mechanisms that cause incompatibility through genetic or chemical manipulation of vector mosquitoes. The proposed research will focus on characterizing proteins and genes that are involved in the mosquito's humoral immune responses, which can lead to the death of parasites. Two proteins that are involved in melanization and killing of ookinetes in Anopheles gambiaewill be cloned and characterized and will be tested for parasite melanization using viral transduction systems. Other proteins and genes that are involved in the responses to parasites will be identified by electrophoretic analysis of in vivo radiolabeled polypeptides and differential display of mRNA molecules produced during parasite infections and humoral immune responses. These molecules will be characterized and tested for parasite-killing ability in vitro and in vivo.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
2R01AI037083-04
Application #
2699975
Study Section
Special Emphasis Panel (ZRG5-TMP (01))
Project Start
1995-09-30
Project End
2003-07-31
Budget Start
1998-08-01
Budget End
1999-07-31
Support Year
4
Fiscal Year
1998
Total Cost
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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