EMAN is a software suite for two and three dimensional image processing of transmission electron microscopy data. Its original design was specifically to perform the compuations required for a technique known as single particle reconstruction. This technique allows the structure of molecules and molecular assemblies in the 10 to 1,000 nanometer range to be fully determined in three dimensions. The molecules and assemblies studied cover the full range of cellular processes. Systems studied using this technique are far too diverse to adequately describe, but some examples include: GroEL, a molecular chaperone, the ribosome, one of the most fundamental assemblies found in all living cells and Ca++ release channel, a critical component in muscle function. This technique has also been crucial in the determination of virus structures, which aid in understanding their function and hence design of new treatments and diagnoses for viral diseases. The computation required to perform these reconstructions is considerable, generally requiring tens to hundreds of thousands of CPU-hours on modern PC clusters to complete. EMAN was designed to automate the reconstruction process to the greatest extent possible to allow higher resolution structures to be obtained, and for the processing to occur more quickly and accurately than previously possible. Since its initial release, the core library has also been used in projects relating to x-ray crystallograpy, electron tomography, structure analysis tools, and molecular visualization. It has also begun to find some use in other high resolution microscopies, such as AFM and image processing of non-biological TEM images. In this proposal we request support to continue to develop and support this package for the benefit of its many hundreds of users worldwide. This will include redeisgn of the core library to make it easier to use by basic scientists through use of an improved Python interface, improvements to documentation and user support, and better cross-platform support. The work this software supports is generally considered basic science, with public health benefits coming from a better understanding of the fundamental processes within the cell. More direct applications of this technique also exist. As one example, for bioterror defence, this technique has been proposed for rapid determination of the structure of an unknown pathogen, allowing rapid identification and distribution of the correct countermeasures. ? ?
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