Peter Rosenthal

Structural Biology of Cells and Viruses

Our group studies the architecture of large protein assemblies in order to understand basic molecular mechanisms that control protein and membrane traffic in the cell and in virus infection.

We apply electron cryomicroscopy and image analysis to study the structure of purified protein complexes in frozen solution, and electron cryotomography to directly image cells in a frozen-hydrated state providing high-resolution images of cell architecture as well as structural information on protein complexes in vivo.

A major focus of the lab is the ultrastructure of viruses. We are interested in understanding how lipid-enveloped viruses such as influenza and retroviruses enter cells by membrane fusion and how new particles are assembled and released by budding through host membranes.

Figure 1

Structural model for a Weibel-Palade body containing von Willebrand factor tubules. (Click to view larger image)

As part of our studies of organelle formation and transformation, we build structural models for Weibel-Palade bodies, which are storage granules for the adhesive blood glycoprotein von Willebrand factor.

We are working to improve experimental methods for high resolution imaging of proteins and to develop new computational procedures for image analysis. We are also interested in designing and imaging nanoscale assemblies with novel functions.

Selected publications

Wasilewski, S and Rosenthal, PB (2014) Web server for tilt-pair validation of single particle maps from electron cryomicroscopy. Journal of Structural Biology 186, 122-131

Sader, K; Stopps, M; Calder, LJ and Rosenthal, PB (2013) Cryomicroscopy of radiation sensitive specimens on unmodified graphene sheets: reduction of electron-optical effects of charging. Journal of Structural Biology 183, 531-536

Calder, LJ; Wasilewski, S; Berriman, JA and Rosenthal, PB (2010) Structural organization of a filamentous influenza A virus. Proceedings of the National Academy of Sciences of the United States of America 107, 10685-10690

Berriman JA, Li S, Hewlett LJ, Wasilewski S, Kiskin FN, Carter T, Hannah MJ, Rosenthal PB. (2009) Structural organization of Weibel-Palade bodies revealed by cryo-EM of vitrified endothelial cells. Proceedings of the National Academy of Sciences of the United States of America 106(41), 17407-17412

Figure 2

Image of influenza virus by electron cryomicroscopy. (Click to view larger image)