Recent advances in Anopheles gambiae transgenic and high throughput genomic technologies have rendered it a powerful model organism for the study of host - parasite interactions and innate immunity. In addition, Anopheline mosquitoes transmit one of the most serious diseases of mankind, malaria. The lack of effective vaccines, the development of parasite resistance to drugs and mosquito resistance to insecticides contribute to the expansion of the disease and have thereby created an acute need for the development of additional novel control strategies. Control strategies based on the blocking of Plasmodium's lifecycle in the vector mosquito will require the understanding of the molecular mechanisms implicated in mosquito - parasite interactions. The mosquito's innate immune system is capable of killing large numbers of malaria parasites. Ingestion of malaria infected blood results in the activation of innate immune responses that contribute significantly to the killing of Plasmodia in the midgut. The specific elicitors of these immune responses, the immune pathways they regulate and their plasmodiocidal activity on the different stages of the parasite are as yet unknown. This application will utilize a full genome microarray for a comprehensive dissection of the systemic and midgut specific transcript responses to the different components (elicitors) that are associated with malaria infected blood and then assess the impact of these responses on Plasmodium development. These analyses will elucidate important aspects of the mosquito's infection responsive physiology and provide information on the regulation of antiplasmodial immune response. It will provide baseline assessment on the utilization of the mosquito's innate immune system for the development of malaria control strategies.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
1R01AI061576-01A1
Application #
6925096
Study Section
Special Emphasis Panel (ZRG1-VB (01))
Program Officer
Costero, Adriana
Project Start
2005-09-30
Project End
2010-03-31
Budget Start
2005-09-30
Budget End
2006-03-31
Support Year
1
Fiscal Year
2005
Total Cost
$211,890
Indirect Cost
Name
Johns Hopkins University
Department
Microbiology/Immun/Virology
Type
Schools of Public Health
DUNS #
001910777
City
Baltimore
State
MD
Country
United States
Zip Code
21218
Kefi, Mary; Mavridis, Konstantinos; Simões, Maria L et al. (2018) New rapid one-step PCR diagnostic assay for Plasmodium falciparum infective mosquitoes. Sci Rep 8:1462
de Mendonça Amarante, Anderson; Jupatanakul, Natapong; de Abreu da Silva, Isabel Caetano et al. (2017) The DNA chaperone HMGB1 potentiates the transcriptional activity of Rel1A in the mosquito Aedes aegypti. Insect Biochem Mol Biol 80:32-41
Simões, Maria L; Dong, Yuemei; Hammond, Andrew et al. (2017) The Anopheles FBN9 immune factor mediates Plasmodium species-specific defense through transgenic fat body expression. Dev Comp Immunol 67:257-265
Simões, Maria L; Mlambo, Godfree; Tripathi, Abhai et al. (2017) Immune Regulation of Plasmodium Is Anopheles Species Specific and Infection Intensity Dependent. MBio 8:
Pike, Andrew; Dong, Yuemei; Dizaji, Nahid Borhani et al. (2017) Changes in the microbiota cause genetically modified Anopheles to spread in a population. Science 357:1396-1399
Saraiva, Raúl G; Kang, Seokyoung; Simões, Maria L et al. (2016) Mosquito gut antiparasitic and antiviral immunity. Dev Comp Immunol 64:53-64
Angleró-Rodríguez, Yesseinia I; Blumberg, Benjamin J; Dong, Yuemei et al. (2016) A natural Anopheles-associated Penicillium chrysogenum enhances mosquito susceptibility to Plasmodium infection. Sci Rep 6:34084
Barletta, Ana Beatriz Ferreira; Alves, Liliane Rosa; Silva, Maria Clara L Nascimento et al. (2016) Emerging role of lipid droplets in Aedes aegypti immune response against bacteria and Dengue virus. Sci Rep 6:19928
Dennison, Nathan J; Saraiva, Raúl G; Cirimotich, Chris M et al. (2016) Functional genomic analyses of Enterobacter, Anopheles and Plasmodium reciprocal interactions that impact vector competence. Malar J 15:425
Bottino-Rojas, Vanessa; Talyuli, Octávio A C; Jupatanakul, Natapong et al. (2015) Heme Signaling Impacts Global Gene Expression, Immunity and Dengue Virus Infectivity in Aedes aegypti. PLoS One 10:e0135985

Showing the most recent 10 out of 58 publications