The aim of this research program is to investigate the anti-hemostatic and anti-inflammatory compounds in the saliva of blood-feeding insects and ticks which allow efficient blood feeding and enhancement of pathogen transmission. Anti-hemostatic compounds of interest include anti-clotting, anti-platelet and vasodilators. Anti-inflammatory compounds include immunomodulatory compounds as well as compounds that modify effector arms of the immune response, such as anti-complement activity found in the saliva of some ticks. While the vector attempts to modify the feeding site to enhance success of blood feeding, such site becomes locally compromised in its ability to react to injury and becomes an easy site for pathogen invasion. On the other hand, when the vertebrate mounts an immune response to these salivary compounds, pathogen transmission may be compromised. Novel pharmaceuticals and novel targets for vaccine development will be ultimate benefits of this program. The work involves obtaining saliva or salivary glands of the insects and ticks under study, bioassay of their biological activity using both in vivo and in vitro tests, purification of the individual activities using chromatographic and electrophoretic techniques, microsequencing of the peptides and proteins, and final identification of the total primary sequence by molecular biology methods. Confirmation of the clones are found by expression in bacterial, yeast, or eukaryotic cell lines. We have initiated a reverse approach where salivary cDNA libraries from blood-feeding insects and ticks are being mass sequenced, providing new insights in the discovery of novel compounds.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Intramural Research (Z01)
Project #
1Z01AI000810-04
Application #
6431690
Study Section
(LPD)
Project Start
Project End
Budget Start
Budget End
Support Year
4
Fiscal Year
2000
Total Cost
Indirect Cost
Name
Niaid Extramural Activities
Department
Type
DUNS #
City
State
Country
United States
Zip Code
Santiago, Paula Beatriz; de Araújo, Carla Nunes; Charneau, Sébastien et al. (2018) Exploring the molecular complexity of Triatoma dimidiata sialome. J Proteomics 174:47-60
Fernández-Medina, R D; Granzotto, A; Ribeiro, J M et al. (2016) Transposition burst of mariner-like elements in the sequenced genome of Rhodnius prolixus. Insect Biochem Mol Biol 69:14-24
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Guo, Yongjian; Ribeiro, Jose M C; Anderson, Jennifer M et al. (2009) dCAS: a desktop application for cDNA sequence annotation. Bioinformatics 25:1195-6
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