Creating Biomedical Technologies to Improve Health

2017 BESIP Project

Biophysics Section and Electron Microscopy Core, Laboratory of Cell Biology
Mentor Name: 
Sriram Subramaniam
Mentor Email: 
Mentor Telephone: 
301-594-2062

Laboratory and Project Description

Recent breakthroughs in the field of cryo-electron microcopy (cryo-EM) provide new prospects for determination of the structures of a variety of medically important macromolecular assemblies. The prospect that the determination of protein structures at atomic resolution will no longer be limited by size, or by the need for crystallization represents a significant and exciting horizon in structural biology. Projects in the lab over the summer will include topics in development of cryo-EM methods for the analysis of structures of medically relevant multi-protein complexes and viruses, with a focus on how these advances can be applied to the development of improved therapeutic agents.
 
Selected recent publications:
  • Merk A., Bartesaghi A, Banerjee S, Falconieri V, Rao P, Davis M, Pragani R, Boxer M, Earl LA, Milne JLS, Subramaniam S (2016) Breaking cryo-EM resolution barriers to facilitate drug discovery. Cell, 165 1698-1707.
  • Matthies D, Dalmas, O, Borgnia, MJ, Dominik, PK, Merk, A, Rao, P, Reddy, BG, Islam, S., Bartesaghi, A, Perozo, E, Subramaniam, S (2016) Cryo-EM Structures of the Magnesium Channel CorA Reveal Symmetry Break Upon Gating. Cell, 164, 747-756.
  • Banerjee, S, Bartesaghi, A, Merk, A, Rao, P. Bulfer, SL, Yan, Y, Green, N, Mroczkowski, B, Neitz, RJ, Wipf, P, Falconieri, V, Deshaies, RJ, Milne, JLS, Huryn D, Arkin, M, Subramaniam S (2016) 2.3 Å resolution cryo-EM structure of human p97 and mechanism of allosteric inhibition. Science, 351,871-875.
  • Meyerson JR, Chittori S, Merk A, Rao P, Han TH, Serpe, M, Mayer ML, Subramaniam S (2016) Structural basis of kainate subtype glutamate receptor desensitization. Nature 537:567-571.
  • Bartesaghi A, Merk A, Banerjee S, Matthies D, Wu X, Milne JLS, Subramaniam S (2015) 2.2 Å resolution cryo-EM structure of b-galactosidase in complex with a cell-permeant inhibitor. Science 348:1147-1151.