: This R21 proposal builds upon the observations made in the RO1 (A1032947-11) which indicates that the expression of TROSPA, a tick receptor for OspA, is up regulated upon infection by Borrelia burgdorferi (B. burgdorferi), the causative agent of Lyme disease. This presumably facilitates Borrelia colonization of the tick midgut. B. burgdorferi likely modulates the tick transcriptome to ensure its survival and transmission. ? ? This aspect of Lyme disease has not been investigated and could open novel venues to vector and disease control. The proposed project aims to broaden the scope of the RO1 and shift the focus beyond TROSPA and OspA. Using cDNA arrays the global changes that occur in the tick salivary gland transcriptome during the infection and transmission of B. burgdorferi will be defined. The functional significance of these gene products in enabling B. burgdorferi invasion of tick salivary glands and its subsequent transmission will be evaluated by specifically silencing the selected tick genes in vivo, using the RNA interference technology. The results of this project will provide insights into tick-Borrelia interactions and enable identification of novel tick -based targets for blocking transmission of Lyme disease. This study will also serve to develop the infrastructure and genetic tools essential for making rapid progress in the field of tick functional genomics. This investigation may therefore serve to pave the way for elucidation of mechanisms underlying transmission of other tick-borne pathogens. ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Exploratory/Developmental Grants (R21)
Project #
1R21AI057940-01
Application #
6712064
Study Section
Special Emphasis Panel (ZRG1-TMP (99))
Program Officer
Baker, Phillip J
Project Start
2004-04-01
Project End
2006-03-31
Budget Start
2004-04-01
Budget End
2005-03-31
Support Year
1
Fiscal Year
2004
Total Cost
$238,900
Indirect Cost
Name
Yale University
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
043207562
City
New Haven
State
CT
Country
United States
Zip Code
06520
Guo, Xiuyang; Booth, Carmen J; Paley, Michael A et al. (2009) Inhibition of neutrophil function by two tick salivary proteins. Infect Immun 77:2320-9
Pedra, Joao H F; Narasimhan, Sukanya; Deponte, Kathleen et al. (2006) Disruption of the salivary protein 14 in Ixodes scapularis nymphs and impact on pathogen acquisition. Am J Trop Med Hyg 75:677-82