Education
09/2009 - 07/2014 Ph.D., School of Life Science, Tsinghua University, Beijing, China
09/2005 - 07/2009 B.S., School of Life Science, Lanzhou University, Lanzhou, China
Professional Experience
08/2020- present, PI, School of Life Science, Peking University
08/2020 - present, PI, Peking-Tsinghua Center for Life Sciences
09/2014 – 07/2020, Postdoc, Wolfgang Baumeister’s Group, Max Planck Institute of Biochemistry, Martinstied, Germany
Honors and Awards
Bayer Investigator, 2021
Boya Young Investigator, 2021
Yifang Investigator, 2020
Humboldt Fellowship， 2016-2017
EMBO Long-term Fellowship，2015-2017
IUCr ( International Union of Crystallography ) First Prize Travel Fellowship，2012
Teaching
Life Sciences and Visual Communication
Cells rely on precisely organized macromolecules to carry out the complex processes of life. These molecular assemblies function like a finely tuned society—where spatial organization, interactions, and structural dynamics dictate cellular behavior. Understanding this "molecular sociology" is key to uncovering how biological systems function in health and fail in disease.
Our research centers on cryo-electron tomography (cryo-ET) and advanced in situ imaging technologies, which provide 3D visualization across nanometer to micrometer scales, bridging the gap between cellular and molecular biology. By combining these techniques with AI-based analysis and multi-omics, we map the architecture, organization, and interactions of molecular machines inside cells. This allows us to deconstruct functional modules and reveal the molecular blueprints of life at unprecedented detail.
Technological Innovations for Mesoscale Biology
To extend the frontiers of in situ imaging, we are developing a versatile, multi-modal framework for quantitative molecular landscape analysis at the mesoscale. Our innovations include:
(a) Topological analysis algorithms: Decoding how molecular organization controls function.
(b) Tissue-compatible in situ imaging workflows: Bringing high-resolution structural biology to complex systems.
(c) High-biocontainment EM facilities: Enabling safe imaging of infectious pathogens.
Biological Applications: From Mechanisms to Pathology
Using our in situ imaging toolkit, we explore how molecular architecture drives both physiology and disease processes. Our current focus areas include:
(a) Mechanisms of cellular motility: Assembly and regulation of molecular motors and motility machinery.
(b) Organelle Morphogenesis: Membrane remodeling and compartmentalization.
(c) Nanoscale Structural Pathology: Cryo-ET analysis of disease-associated ultrastructural changes
By combining cutting-edge in situ imaging with analytical approaches, we aim to decode the molecular logic of life—from fundamental mechanisms to therapeutic insights.
* co-first authors, # corresponding author
Wang, C.*, Jiang, W.*, Leitz, J.*, Yang, K., Esquivies, L., Wang, X., Shen, X., Held, R., Adams, D.J., Basta, T., Hampton, L., Jian, R., Jiang, L., Stowell, M.H.B., Baumeister, W., Guo, Q.#, Brunger, A.T.#, (2024). Structure and topography of the synaptic V-ATPase–synaptophysin complex. Nature.
Liu, J.*, Li, Z.*, Li, M.*, Du, W., Baumeister, W., Yang, J.#, and Guo, Q.# (2023). Vimentin regulates nuclear segmentation in neutrophils. Proceedings of the National Academy of Sciences 120, e2307389120.
Wu, Y.*, Qin, C.*, Du, W.*, Guo, Z., Chen, L., Guo, Q.# (2023). A practical multicellular sample preparation pipeline broadens the application of in situ cryo-electron tomography. Journal of Structural Biology, 107971.Cover Story.
Li, Z., Du, W., Yang, J., Lai, D.-H., Lun, Z.-R., Guo, Q.# (2023). Cryo-Electron Tomography of Toxoplasma gondii Indicates That the Conoid Fiber May Be Derived from Microtubules. Advanced Science 10, 2206595. Cover Story.
Saha, I., Yuste-Checa, P., Da Silva Padilha, M., Guo, Q., Körner, R., Holthusen, H., Trinkaus, V.A., Dudanova, I., Fernández-Busnadiego, R., Baumeister, W., Sanders, D.W., Gautam, S., Diamond, M.I., Hartl, F.U.#, Hipp, M.S.#, (2023). The AAA+ chaperone VCP disaggregates Tau fibrils and generates aggregate seeds in a cellular system. Nature Communications 14, 560.
Li, W.*, Lu, J.*, Xiao, K.*, Zhou, M.*, Li, Y., Zhang, X., Li, Z., Gu, L., Xu, X., Guo, Q.#, Xu, T.#, Ji, W.#, (2023). Integrated multimodality microscope for accurate and efficient target-guided cryo-lamellae preparation. Nature Methods 20, 268-275.
Jiang, W., Wagner, J., Du, W., Plitzko, J., Baumeister, W., Beck, F.#, and Guo, Q.# (2022). A transformation clustering algorithm and its application in polyribosomes structural profiling. Nucleic Acids Research 50, 9001-9011. Cover Story
Riemenschneider, H.*, Guo, Q.*, Bader, J., Frottin, F., Farny, D., Kleinberger, G., Haass, C., Mann, M., Hartl, F.U., Baumeister, W. et al. (2022) Gel-like inclusions of C-terminal fragments of TDP-43 sequester stalled proteasomes in neurons. EMBO Reports, 23, e53890
Peters, J.J., Leitz, J., Guo, Q., Beck, F., Baumeister, W. and Brunger, A.T. (2022) A feature-guided, focused 3D signal permutation method for subtomogram averaging. Journal of Structural Biology, 214, 107851
Huang, B.*, Guo, Q.*, Niedermeier, M.L., Cheng, J., Engler, T., Maurer, M., Pautsch, A., Baumeister, W., Stengel, F., Kochanek, S., et al. (2021). Pathological polyQ expansion does not alter the conformation of the Huntingtin-HAP40 complex. Structure 29, 804-809.e805.
Trinkaus, V.A., Riera-Tur, I., Martínez-Sánchez, A., Bäuerlein, F.J.B., Guo, Q., Arzberger, T., Baumeister, W., Dudanova, I., Hipp, M.S., Hartl, F.U., et al. (2021). In situ architecture of neuronal α-Synuclein inclusions. Nature Communication. 12, 2110.
Seefelder, M., Alva, V., Huang, B., Engler, T., Baumeister, W., Guo, Q., Fernandez-Busnadiego, R., Lupas, A.N., and Kochanek, S. (2020). The evolution of the huntingtin-associated protein 40 (HAP40) in conjunction with huntingtin. BMC Evolutionary Biology 20, 162
Yasuda, S., Tsuchiya, H., Kaiho, A., Guo, Q., Ikeuchi, K., Endo, A., Arai, N., Ohtake, F., Murata, S., Inada, T., et al. (2020). Stress- and ubiquitylation-dependent phase separation of the proteasome. Nature 578, 296–300.
Guo, Q.*, Bin, H.*, Cheng, J., Seefelder, M., Engler, T., Pfeifer, G., Oeckl, P., Otto, M., Moser, F., Maurer, M., Pautsch, A., Baumeister, W.#, Fernandez-Busnadiego, R.#, Kochanek, S.# (2018). The cryo-electron microscopy structure of huntingtin. Nature 555, 117–120.
Guo, Q., Lehmer, C., Martinez-Sanchez, A., Rudack, T., Beck, F., Hartmann, H., Hipp, M.S., Hartl, F.U., Edbauer, D.#, Baumeister, W.#, Fernandez-Busnadiego, R#. (2018) In Situ Structure of Neuronal C9orf72 Poly-GA Aggregates Reveals Proteasome Recruitment. Cell 172, 696-705.e612.
Zhao, Y., Zeng, X., Guo, Q., and Xu, M. (2018). An integration of fast alignment and maximum-likelihood methods for electron subtomogram averaging and classification. Bioinformatics 34, i227-i236.
Li, Z., Guo, Q., Zheng, L., Ji, Y., Xie, Y.T., Lai, D.H., Lun, Z.R., Suo, X., and Gao, N. (2017). Cryo-EM structures of the 80S ribosomes from human parasites Trichomonas vaginalis and Toxoplasma gondii. Cell Research 27, 1275-1288.
Mi, N., Chen, Y., Wang, S., Chen, M., Zhao, M., Yang, G., Ma, M., Su, Q., Luo, S., Shi, J., Xu, J., Guo, Q., et al. (2015). CapZ regulates autophagosomal membrane shaping by promoting actin assembly inside the isolation membrane. Nature Cell Biology 17, 1112-1123.
Feng, B., Mandava, CS., Guo, Q., Wang, J., Cao, W., et al. (2014) Structural and Functional Insights into the Mode of Action of a Universally Conserved Obg GTPase. PLoS Biology 12(5): e1001866.
Yang, Z.*, Guo, Q.*, Goto, S., Chen, Y., Li, N., Muto, A., Himeno, H., Deng, H., Lei, J.#, and Gao, N.# (2014). Characterization of the in vivo 30S ribosomal assembly intermediates reveals essential role of S5 and location of unprocessed ends of the 17S rRNA. Protein Cell 5, 394-407.
Li, N., Chen, Y., Guo, Q., Zhang, Y., Yuan, Y., Ma, C., Deng, H., Lei, J.#, and Gao, N.# (2013). Cryo-EM structures of the late-stage assembly intermediates of the bacterial 50S ribosomal subunit. Nucleic Acids Research 41, 7073-7083.
Guo, Q.*, Goto, S.*, Chen, Y.*, Feng, B., Xu, Y., Muto, A., Himeno, H., Deng, H., Lei, J., and Gao, N. (2013). Dissecting the in vivo assembly of the 30S ribosomal subunit reveals the role of RimM and general features of the assembly process. Nucleic Acids Research 41, 2609-2620.
Huang, W.*, Choi, W.*, Hu, W., Mi, N., Guo, Q., Ma, M., Liu, M., Tian, Y., Lu, P., Wang, F.L., et al. (2012). Crystal structure and biochemical analyses reveal Beclin 1 as a novel membrane binding protein. Cell Research 22, 473-489.
Guo, Q.*, Yuan, Y.*, Xu, Y., Feng, B., Liu, L., Chen, K., Sun, M., Yang, Z., Lei, J.#, and Gao, N.# (2011). Structural basis for the function of a small GTPase RsgA on the 30S ribosomal subunit maturation revealed by cryoelectron microscopy. PNAS 108, 13100-13105.
We are an in situ Structural Biology lab, we study Cellular Architecture—how
subcellular compartments build up a functional cell, and Macromolecule
Sociology—what’s the relationship between macromolecules and organelles.
Cryo-electron tomography (Cryo-ET) is a
cutting-edge technique that allows the study of protein function in their
physiological cellular context and, via subtomogram averaging technique, at
molecular resolution. The development of correlative cryo-light and electron
microscopy (CLEM) and focused ion beam (FIB) allows precise thinning of
vitrified cells to target the region of interest. Based on these state-of-the-art
techniques our research focus:
To capture molecular snapshots
of fundamental cellular processes in their physiological context.
To better understand the
structural mechanisms of human diseases, especially aging related degenerative
diseases.
To optimize a practical
workflow for high resolution in situ structural biology.
