Genome Research

Structural Biology at the Advanced Light Source

With the completion of the sequencing of the human genome, biotechnology has developed extremely rapidly to take advantage in the explosion of information available. However, it is generally accepted that many advances can only occur when the massive volume of genomic information is complemented by advances in our understanding of the functions of genes and gene products at a molecular level. Determination of the structures of proteins and macromolecular complexes provides crucial input to aid our understanding of molecular function, and is a key component in extending this functional understanding into rational structure-based drug design. The Physical Biosciences Division's research in protein crystallography and related technologies is centered at the Berkeley Center for Structural Biology (BCSB). This program is located at the Advanced Light Source (ALS); a national user facility funded by the U.S. Department of Energy's Office of Basic Energy Sciences. The ALS generates intense light for scientific and technological research and is the world's brightest source of ultraviolet and soft x-ray beams. The Berkeley Center for Structural Biology (BCSB) currently administers six protein crystallography beamlines at the ALS and is building two more. Researchers in this center support beamline operations to enable an international community of researchers to successfully collect data and therefore solve protein structures. Within the center, there are individual research programs in the areas of Wnt receptor pathway, 70S ribosome studies, eukaryotic transcription complexes and amelogenin protein studies.

Structural Biology at the Berkeley Structural Genomics Center

The Berkeley Structural Genomics Center (BSGC) is one of nine national pilot centers funded by the Protein Structure Initiative (PSI). The PSI project (which is administered by the National Institutes of Health) is designed to organize a cooperative, large-scale effort in the emerging field of structural genomics. Structural genomics seeks to discover all or most of the protein folding repertoire in nature, and to understand the relationship between protein structure and function and gene sequence. With applications in the life sciences, biotechnology, and medicine, the protein structural data generated by the efforts of the BSGC (and the other centers) can serve as a basis for the development of medicines, vaccines, and diagnostics. The inaugural project of the center is designed to obtain a near-complete structural compliment of two small genomes, Mycoplasma genitalium and Mycoplasma pneumonia, notable for their minimal genomes and relevance to human disease.

Components:

Target Selection, Data Management led by Steven Brenner

Cloning, Expression led by Rosalind Kim

X-Ray Crystallography led by Sung-Hou Kim

NMR led by David Wemmer

Hardware Development led by Thomas Earnest

Software Development led by Paul Adams

Correlation to Cellular Function led by Clyde Hutchison

Expression system led by David McKay