Joachim Frank

Columbia University

Primary Section: 29, Biophysics and Computational Biology
Secondary Section: 22, Cellular and Developmental Biology
Membership Type: Member (elected 2006)

Research Interests

Originally trained as a physicist, I developed an interest in methods to investigate biological structures with the transmission electron microscope. Using the novel technique of cryo-EM single-particle reconstruction which my group pioneered, I'm studying the mechanism of protein synthesis in bacteria and eukaryotes in collaborations with leading groups in ribosome biochemistry. In appropriate buffer, ribosomes complexed in vitro with mRNA, tRNAs and protein factors are functionally active, and can be stalled in defined states by the use of antibiotics or nonhydrolyzable GTP analogs. Electron micrographs of such complexes embedded in vitreous ice, taken with low dose, are processed to obtain three-dimensional density maps at a resolution ranging between 8 and 12 angstroms. In this way, the binding positions of initiation, elongation, and release factors on the ribosome have been revealed. Fitting of X-ray structures into these maps shows evidence of conformational changes during translation, indicating that the interaction between the ribosome and its ligands is highly dynamic. Important processes that cryo-EM has helped to elucidate include the way viral RNA (IRES) enters the ribosome, and the mechanism of protein export.

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