Electron microscopy only captures the two dimensional image of a sample in a fixed position, so in order to create a three dimensional reconstruction of an isolate macromolecule, a large amount of images taken from different angles are needed.  Subsequently, an even larger data set of asymmetric units will be needed to produce the three dimensional image out of the information gathered in the numerous two dimensional images.  For example, a data set of approximately 100,000 asymmetric unit can produce a three dimensional reconstruction at 8 -12Å resolution, which is sufficient to insert atomic-resolution models of component macromolecules, whose structure would have been determined previously by other methods (such as X-ray or electron crystallography, or NMR spectroscopy). Even larger data sets (at least one million asymmetric units) are needed to achieve resolutions better than 5Å, and ultimately to obtain 3-D reconstructions at about 3.5Å, the resolution needed for de novo determination of an atomic structure.

The size of the data obviously poses a problem.  It is too large and therefore would take an unfeasible amount of time to calculate with currently available software on a single workstation, which often require, to a certain degree, manual operations.  This rate limiting factor is what keeps electron microscopy from becoming the ideal technology involved in structural biology. 

This is where the Computational Technology for High-Throughput Cryo-Electron Microscopy program project comes into the picture.  This program project was proposed in response to the National Institute of Health's program announcement "Technology Development for High Resolution Electron Microscopy" (PA-00-084) and might provide a possible solution to the above mentioned problem. It is funded by the NIH and granted $7,536,250 for a duration of five years (December 1, 2001~November 30, 2006).  The main organizations involved in the program project are: Lawrence Berkeley National Laboratory, Baylor College of Medicine, Houston Medical School of the University of Texas, and Wadsworth Center of NYS Department of Health.

The program project is named thus because it is divided into several individual research projects which would all benefit the common cause and contribute to the final result of the program project.  It involves scientists from mainly the fields of structural biology and scientific computing. The principal investigator of the overall project management is Robert M. Glaeser of LBL. Other project directors include Joachim Frank of Wadsworth Center in New York (project A), Steven Ludtke of Baylor College of Medicine and Paul D.  Adams of LBL (project B), Esmond Ng of LBL (project C), Ravi Malladi of LBL (project D),  Pawel A Penczek of Houston Medical School (project E), Wah Chiu of Baylor (core F, along with Dr. Glaeser), and associated principal investigators from various research groups (project G)

To read more about our key personnels and individual projects, go to Directors and  Research Projects