Centers and Institutes   |
As a protein chemist at LLNL since 1993, Dr. Michael Thelen has investigated the cellular response to environmental agents causing DNA damage, focusing on several novel proteins and protein complexes central to DNA repair and recombination. More recently his research has turned towards natural ecosystems to identify proteins important for survival in unusually harsh conditions. Michael spent the year of 2004 as a visiting scholar in Jill Banfield’s geobiology group at the University of California, Berkeley, characterizing proteins from the unique microbial communities of an extremely acidic environment. In July 2006 he was a guest research scientist on the Atlantis cruise along the California/Oregon coast, to collect and study organisms from deep methane seep ecosystems. The research in his group is funded by the Department of Energy’s Genomics: Genomes to Life Program.
Michael Thelen’s laboratory group is interested in the molecular mechanisms of microbial adaptation and interaction with extreme environments, such as acidic and metal-rich mine waters. Proteins specialized for such conditions are important in processes that are essential to the organism and community, including energy acquisition (e.g., iron and sulfide oxidation), biofilm formation (extracellular polymer synthesis and metabolism), DNA repair (oxygen radical damage), and strain/species evolution (genetic recombination). The current challenges are to isolate these atypical proteins directly from the environment, identify them using proteogenomics, and elucidate protein functions using biochemistry, molecular biology, and computational structure prediction.
Peptide mapping: evidence of recombination
Lo, I., V. J. Denef, N. C. VerBerkmoes, M. B. Shah, D. Goltsman, G. DiBartolo, G. W. Tyson, E. E. Allen, R. J. Ram, J. C. Detter, P. Richardson, M. P. Thelen, R. L. Hettich, and J. F. Banfield, "Strain-Resolved Community Proteomics Reveals Recombining Genomes of Acidophilic Bacteria," Nature 446, 537-41 (2007).
Ram, R. J., N. C. VerBerkmoes, M. P. Thelen, G. W. Tyson,
B. J. Baker, R. C. Blake II, M. Shah, R. L. Hettich, and J. F. Banfield, "Community
Proteomics of a Natural Microbial Biofilm," Science
308, 1915-20 (2005).
|Model of BRCT domain complex|
Beernink, P. T., M. Hwang, M. Ramirez, M. B. Murphy, S. A. Doyle, and M.
of Protein Interactions Mediated by BRCT Domains,"
J Biol Chem 280, 30206-13 (2005).
|Structure determination of a BRCT domain|
Krishnan, V. V., K. H. Thornton, M. P. Thelen, and M. Cosman, "Solution
Structure and Backbone
Dynamics of the Human DNA Ligase III α BRCT Domain," Biochemistry 40, 13158-66 (2001).
Venclovas, Č., M. Colvin, and M. P. Thelen, "Molecular Modeling-Based Analysis of Interactions in the RFC-Dependent Clamp-Loading Process," Protein Science 11, 2403-16 (2002).
Venclovas, Č., and M. P. Thelen, "Structure-Based Predictions of Rad1, Rad9, Hus1 and Rad17 Participation in Sliding Clamp and Clamp Loading Complexes," Nucleic Acids Research 28, 2481-93 (2000). Cover Article.
Thelen, M. P., Č. Venclovas, and K. Fidelis, "A Sliding Clamp Model for the Rad1 Family of Cell Cycle Checkpoint Proteins," Cell 96, 769-70 (1999).