Prof. Robert M. Glaeser
Professor of Biochemistry & Molecular Biology
Research Interests
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We are interested in the high-resolution molecular structure of cell membrane proteins, and we seek to understand the biochemical function of these systems at the level of molecular biophysics. Our primary research methods include high-resolution electron microscopy of single-molecule specimens, electron diffraction of two-dimensional crystals, X-ray diffraction of three dimensional crystals, and spectroscopic techniques.
Current Projects
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We are currently conducting basic studies on the mechanism of crystallization of membrane proteins, using various lipidic bilayer gels as the host-matrix. This direction of work has evolved from previous work, cited below, which was conducted over the past several years. In this previous work, wt bacteriorhodopsin (bR) and a number of mutants of bR were crystallized from the three-dimensionally connected gels of lipid bilayers that are formed by hydrated monoglycerides. The work with mutants of bR made us aware, however, that at least some membrane proteins are actually less stable in the monoglyceride gels than they are when solubilized in detergent. Alerted by this unexpected finding, we have found a solution to the problem of stability of the more labile mutants after reconstitution into the hydrated lipid gels. Numerous avenues are now being explored that could transform the technology such that membrane proteins would finally be included as part of the structural genomics initiative that is already well under way for soluble proteins.
Single-particle electron cryo-microscopy represents a potential alternative for high-throughput structure analysis, particularly for large macromolecular assemblies. The frontier of this technology is directed toward extending the capabilities to record and process data, which currently involves only tens of thousands of single particles. We are developing tools for automation of data collection in the electron microscope, with the goal of increasing the size of data sets to include hundreds of thousands, or even a few million particles. At the same time we are also developing highly parallelized and automated software tools to carry out the processing and merging of these data. The aim is to achieve atomic-resolution structures of detergent-solubilized membrane proteins without requiring crystallization of the sample.
Research Description/Selected Publications: http://mcb.berkeley.edu/faculty/BMB/glaeserr.html
Mailing address:
Glaeser Lab
University of California, Berkeley
Department of Molecular & Cell Biology
237 Hildebrand Hall #3206
Berkeley, CA 94720-3206
E-mail: rmglaeser@lbl.gov
Office: 363B Donner Lab
Phone: (510) 642-2905
Fax: (510) 486-6488