The overall goal of the proposed research is to significantly enhance our present understanding of the properties of rickettsiae, a group of obligately intracellular, arthropod transmitted, bacteria which cause at least eleven human diseases in different parts of the world. Orientia tsutsugamushi, Rickettsia akari, R. canada, and R. bellii will be studied. The complete genome sequences of these organisms will be determined to 99.99% accuracy and analyzed by computer to identify the putative RNA, protein encoding genes, pseudogenes, repeat elements, 'selfish DNA', and regulatory elements present in each organism. This information will be provided in publicly accessible databases. Unique and conserved genetic elements found in each rickettsia will be compared to help understand the mechanisms underlying evolution of their pathogenic adaptations. This initial in silico analysis requires biochemical confirmation as it depends upon the similarity of rickettsial gene sequences to well-characterized genetic elements found in other bacteria. Less than 15 of the 1000-2000 genes expected to be present in each of these species have been studied previously. Because of the intracellular lifestyle of rickettsiae and the lack of genetic systems, conventional approaches to characterization of the functional properties of these genes in rickettsiae are limited. Bacterial artificial chromosome (BAC) libraries and DNA arrays containing each gene will be constructed for each rickettsial genome. The BACs and DNA arrays will be used to characterize the expression and regulation of rickettsial genes. Selected rickettsial proteins that may be useful in vaccine development and as potential therapeutic targets will be cloned and expressed to facilitate their characterization. ? ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
1R01AI053264-01
Application #
6559545
Study Section
Special Emphasis Panel (ZRG1-EVR (01))
Program Officer
Perdue, Samuel S
Project Start
2003-01-15
Project End
2003-07-31
Budget Start
2003-01-15
Budget End
2003-07-31
Support Year
1
Fiscal Year
2003
Total Cost
$456,923
Indirect Cost
Name
Institute for Systems Biology
Department
Type
DUNS #
135646524
City
Seattle
State
WA
Country
United States
Zip Code
98109
Philibert, Robert A; Crowe, Raymond; Ryu, Gi-Yung et al. (2007) Transcriptional profiling of lymphoblast lines from subjects with panic disorder. Am J Med Genet B Neuropsychiatr Genet 144B:674-82
Philibert, Robert; Madan, Anup; Andersen, Allan et al. (2007) Serotonin transporter mRNA levels are associated with the methylation of an upstream CpG island. Am J Med Genet B Neuropsychiatr Genet 144B:101-5
Philibert, Robert A; Ryu, Gi-Yung; Yoon, Jae-Geun et al. (2007) Transcriptional profiling of subjects from the Iowa adoption studies. Am J Med Genet B Neuropsychiatr Genet 144B:683-90
Philibert, Robert A; Madan, Anup (2007) Role of MED12 in transcription and human behavior. Pharmacogenomics 8:909-16