Bioscience Division, Mail Stop M888, Los Alamos National Laboratory, Los Alamos, NM 87545
Tel.: (505) 667-0072 Email: email@example.com
Structural biology research interests
Methods development for macromolecular crystallography
Our group and our colleagues have developed algorithms and software for analyzing X-ray diffraction data from macromolecules such as proteins and nucleic acids and determining their 3-dimensional structures. Our group is part of the collaborative PHENIX project, an effort led by Paul Adams at LBL that is producing a comprehensive software package for macromolecular structure determination. The PHENIX package includes my SOLVE/RESOLVE software as well as many additional powerful algorithms, including maximum-likelihood molecular replacement (Randy Read's Phaser software), full maximum-likelihood refinement (Paul Adams, Ralf Grosse-Kunstleve, and Pavel Afonine's phenix.refine), model improvement and validation (the Richardson laboratory's Molprobity software) and many other useful tools. The PHENIX software is available free for academic users.
Structural Biology of Bacterial Efflux Pumps
We are part of a multidisciplinary team focused on understanding how bacteria can pump antibiotics out of the cell and prevent the antibiotics from working. We hope that this understanding may help in developing new drugs that will restore the efficacy of existing antibiotics by blocking these pumps. Our role in this project is to determine structures of the bacterial efflux pumps and their components, focusing on pumps from the pathogenic bacteria Burkholderia pseudomallei but also including other related pumps. As a preliminary part of this work we recently determined the structure of an E. coli AcrB pump component bound to the antibiotic Linezolid (Hung et al., 2013).
Proteins are the molecular machines of life, and a knowledge of their three-dimensional structures is crucial for understanding how they work. A main focus of our laboratory is determining and analyzing the structures of proteins. Our group, along with structural biologists around the world, recognized in the late 1990s that a large-scale effort to determine structures of thousands of proteins could have a profound effect on the understanding of biology. The U.S. Department of Energy and later the National Institutes of Health (the NIH Protein Structure Initiative) have funded our Los Alamos structural genomics team and others around the US to develop and apply technologies for large-scale structure determination. Structural genomics was a major worldwide effort over the past 15 years, and in 2001 our group helped found the International Structural Genomics Organization (ISGO) in order to promote international cooperation in structural genomics.
The TB Structural Genomics Consortium (TB SGC)
The TB Structural Genomics Consortium is a worldwide consortium of scientists from around the world devoted to determining structures of proteins from the pathogenic organism M. tuberculosis. Our group founded and led the TB SGC for its first 5 years as part of phase 1 of the NIH Protein Structure Initiative. Now the TB SGC continues as an NIAID-funded project led by Jim Sacchettini at Texas A&M University, with Los Alamos as an active member. The TB Structural Genomics Consortium has solved over a hundred structures of M. tuberculosis proteins already. We hope that these structures will form a foundation for drug discovery that will lead to improved anti-TB therapy.
The Los Alamos Structural Genomics team
(see http://www.lanl.gov/source/projects/gfp/ for details about GFP reporter systems)
Cloning and Protein Production
X-ray Data Collection and Analysis (ALS; Lawrence Berkeley National Laboratory)