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What happens to a cell when it gets infected with a virus?
Viruses are intracellular parasites that remodel host cells into virus factories, exploiting cellular metabolism and repurposing signaling pathways. At the same time, viruses must constantly evade the host's immune system.
Through the power of evolutionary pressure, viruses have turned into the ideal cell biologists. Studying virus-host systems offers us a unique perspective to understanding the fundamental principles of the organization of life at the molecular level.
In the long term, a better understanding of the principles of virus-host interactions will also help in the development of drugs to combat viral replication, as well as the prevention of an overactive immune response.
Two aspects of virus-host biology are particularly informative for a comprehensive understanding of the processes within an infected cell: (1) The repurposing and/or counteracting of host pathways by the virus. (2) the physical reorganization of the host cell upon infection. We study those complementary aspects using cutting-edge technology.
We use CRISPR-based genetic perturbations combined with a single-cell transcriptomics readout to functionally connect host pathways with the stages of the viral life cycle where they play a role. Moreover, we develop proteomics methods to map subcellular architecture and its dynamics upon infection.
Our overall goal is to design systems-level experiments that yield systems-level insight, going beyond what one can see by studying one gene or protein at a time.
Marco obtained his PhD working with Matthias Mann at the Max Planck Institute of Biochemistry, where he used proteomics to map the human protein interactome. As an EMBO postdoc with Jonathan Weissman at the University of California, San Francisco, he studied virus-host interactions using single-cell functional genomics. After a stint as a Fellow at the Chan Zuckerberg Biohub, Marco established his lab in Vienna in November 2022.
We used Perturb-seq to map the phenotypic landscapes of host factors of SARS-CoV-2, characterizing what happens to the course of infection when host factors are inactivated. Two classes of factors stood out: factors involved in entry or early events, and those mediating the interferon response (Sunshine et al., Nature Communications, 2023)
Interview with Marco Hein about the excitement of discovering something new and what can be learned from viruses about cells and from viral pandemics about science.
We studied the infection of cytomegalovirus in human cells by a novel, functional single-cell genomics approach (Hein & Weissman, Nature Biotechnology, 2021). Our results reveal a dichotomy between the roles of host and viral factors: viral factors define the trajectory of infection and host factors create the environment permitting the execution of that program.
Proud to be part of team OpenCell! Combining endogenous protein tagging, live-cell microscopy and interaction proteomics, we studied the physical and functional organization of the human proteome. Browse the resource at opencell.czbiohub.org and read the paper (Cho et al., Science, 2022)
Functional single-cell genomics of human cytomegalovirus infection.
Hein, Marco Y; Weissman, Jonathan S
OpenCell: Endogenous tagging for the cartography of human cellular organization.
Cho, Nathan H; Cheveralls, Keith C; Brunner, Andreas-David; Kim, Kibeom; Michaelis, André C; Raghavan, Preethi; Kobayashi, Hirofumi; Savy, Laura; Li, Jason Y; Canaj, Hera; Kim, James Y S; Stewart, Edna M; Gnann, Christian; McCarthy, Frank; Cabrera, Joana P; Brunetti, Rachel M; Chhun, Bryant B; Dingle, Greg; Hein, Marco Y; Huang, Bo; Mehta, Shalin B; Weissman, Jonathan S; Gómez-Sjöberg, Rafael; Itzhak, Daniel N; Royer, Loïc A; Mann, Matthias; Leonetti, Manuel D
Mapping transcriptomic vector fields of single cells.
Qiu, Xiaojie; Zhang, Yan; Martin-Rufino, Jorge D; Weng, Chen; Hosseinzadeh, Shayan; Yang, Dian; Pogson, Angela N; Hein, Marco Y; Hoi Joseph Min, Kyung; Wang, Li; Grody, Emanuelle I; Shurtleff, Matthew J; Yuan, Ruoshi; Xu, Song; Ma, Yian; Replogle, Joseph M; Lander, Eric S; Darmanis, Spyros; Bahar, Ivet; Sankaran, Vijay G; Xing, Jianhua; Weissman, Jonathan S