(Georgia Institute of Technology, 2008-09-22)
Carragher, Bridget
Over the past decade, cryo-electron microscopy (cryoEM) has emerged as a powerful approach to the structural determination of large macromolecular complexes. Elucidating the structure and mechanism of action of these "molecular machines" is an emerging frontier in understanding how the information in the genome is transformed into cellular activities. In cryoEM the macro molecular specimen is preserved in a thin layer of vitreous (glassy) ice and imaged in the electron microscope using very low doses of electrons. The low signal to noise ratio of the resulting images means that averaging is required to recover the signal and reconstruct a three dimensional map of the structure. Our goal is to develop a pipeline to automate the processes involved in solving macromolecular structures using cryo-electron microscopy. One of the goals of the pipeline is to enable much higher data throughputs and improve the resolution of single particle reconstructions. We are also using the pipeline to help understand what currently limits resolution in these maps. The current status of these efforts will be illustrated using a variety of macromolecules as case studies.