Xiaojie Zhang: 'Expect the unexpected in cellular cryo-electron tomography: the story of our...'

Xiaojie Zhang (EMBL Heidelberg) will present "Expect the unexpected in cellular cryo-electron tomography: the story of our discovery of stress-induced mumps virus reactivation."

Abstract: In contrast to conventional membrane-bound cellular organelles, biomolecular condensates are cellular compartments assembled via phase separation and are involved in many cellular processes, ranging from cell signaling to transcriptional regulation in diverse cell types. However, the structural basis for the organization and dynamics of such cellular condensates remains largely unknown. In the past years, our lab developed an efficient cellular cryo-electron tomography (ET) pipeline involving cryo-focused ion beam sample preparation, which allows visualization of cellular compartments at sub-nanometer resolution. In particular, a correlative cryo-fluorescence light and electron microscopy approach faithfully allows targeting of cellular condensates which don’t have membrane boundaries that serve as prior knowledge about their structural features. Cellular cryo-ET on such preparations then bridges spatial resolutions for understanding organelle-organelle interactions to unraveling functional states of macromolecular machineries in their unperturbed cellular context. I will present our unexpected discovery of persistent mumps virus infection in a HeLa cell model, enabled by cellular cryo-ET in combination with quantitative mass spectrometry. We identified stress-induced reactivation of mumps virus and revealed the corresponding cellular, molecular, and structural changes within the viral replication factories which are one type of biomolecular condensates. Our case study shows the power of cellular cryo-ET for structural characterization of novel intricate molecular events in their native cellular environment.

The Optical Interest Group (OIG) seminar series is coordinated by Ulrike Boehm and Chen Wang.