Marco Hein

Systems Biology & Viruses

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The Question

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.

The Approach

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.

Biography

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 short tenure as a Fellow at the Chan Zuckerberg Biohub, Marco established his lab in Vienna in November 2022.

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Spotlights

Global organelle profiling reveals subcellular localization and remodeling at proteome scale

With Manu Leonetti's group at the Chan Zuckerberg Biohub, we used immunoprecipitation of intact organelles to map the subcellular localization of the majority of proteins in human cells, and the dynamics of the subcellular proteome upon viral infection with HCoV-OC43.

Browse the resource at organelles.czbiohub.org and read our paper (Hein et al., Cell, 2025)

The Vienna Science and Technology Fund (WWTF) funded our proposal "Deconstructing and Reconstructing Anelloviruses".
Our lab, together with the group of Irene Görzer at the MedUni Center for Virology, will receive 900,000 Euros for four years.
Anelloviruses are ubiquitous viruses that infect virtuall all humans, apparently without causing disease. We're eager to shed light on the almost entirely unknown cell biology of these viruses. 

Read more about the proposal and the other projects funded as part of the "Life Sciences 2024 - Synthetic Biology" call.

Systematic characterization of SARS-CoV-2 host factors

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.

Functional single-cell genomics of HCMV infection

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.

OpenCell: Cartography of human cellular organization

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)

    Team

    Marco Hein
    Group Leader
       +43 1 4277 61710
    Room: 2.116

    Julius Kühn
    Master Student
       +43 1 4277 61710
    Room: 2.110

    Sebastian Platzer
    PhD Student
       +43 1 4277 61809
    Room: 2.110

    Leon Schmidt
    Master Student
       +43 1 4277 61810
    Room: 2.110

    Kavya Shetty
    PhD Student
       +43 1 4277 61809
    Room: 2.110

    Selected Publications

    Functional single-cell genomics of human cytomegalovirus infection.

    2022 Nature biotechnology(3)
    PMID:  34697476

    Hein Marco Y, Weissman Jonathan S

    OpenCell: Endogenous tagging for the cartography of human cellular organization.

    2022 Science (New York, N.Y.)(6585)
    PMID:  35271311

    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.

    2022 Cell(4)
    PMID:  35108499

    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

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