Numerous members of the third kingdom, Archaea, are extreme hyperthermophiles. Such organisms pose many interesting fundamental questions in molecular biology, since all of their life processes occur at elevated temperatures. For instance, how do regulatory proteins recognize and bind to operators at temperatures above 100 degrees C? How can the DNA replicate with high fidelity, and how do these organisms avoid excessive mutation due to heat-induced DNA lesions, and what repair strategies do they employ? We propose to develop a functional genomic analysis of one of the high temperature archaea, Pyrobaculum aerophilum, that can grow up to 104 degrees C, with an optimal growth temperature of 100 degrees C. We have sequenced and fully annotated the 2.2 mega base genome of Pyrobaculum aerophilum, and are completing the construction of microarrays containing every ORF, in collaboration with Todd Lowe at Stanford/U.C. Santa Cruz. We will carry out experiments on genome-wide gene expression in different environments, and use the data to identify coregulated genes. Through extended analyses, we hope to use the data to set up experiments to identify regulatory pathways and regulatory proteins. We will extend the development of a genetic system with the aim of being able to carry out reverse genetics in this organism. We have begun an indepth investigation of the repair systems in this organism, and we will continue to characterize DNA repair strategies and proteins.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM057917-07
Application #
6784738
Study Section
Genome Study Section (GNM)
Program Officer
Anderson, James J
Project Start
1998-08-01
Project End
2006-07-31
Budget Start
2004-08-01
Budget End
2005-07-31
Support Year
7
Fiscal Year
2004
Total Cost
$305,000
Indirect Cost
Name
University of California Los Angeles
Department
Microbiology/Immun/Virology
Type
Schools of Medicine
DUNS #
092530369
City
Los Angeles
State
CA
Country
United States
Zip Code
90095
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