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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.
With Manu Leonetti's group at the Chan Zuckerberg Biohub, we developed an approach to map the subcellular locations of virtually all the proteins in human cells. Browse the resource at organelle.czbiohub.org and read our Preprint to find out more about how we mapped protein relocalization upon infecting the cells with the coronavirus hCoV-OC43.
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
VBC Industry Insights x BioNTech RandD Austria
Profiling and programming in vitro human neuronal diversity at single-cell resolution
18th Microsymposium on RNA Biology
The „Microsymposium on RNA Biology“ is an international conference that brings together young scientists, junior and senior group leaders, and company representatives from all over the world to present and discuss their latest findings in the exciting field of small RNAs and beyond. The Microsymposium was founded in 2005 and has established itself as the major small RNA meeting in Europe. It is organized by the four research institutions IMBA, IMP, GMI and the Max Perutz Labs as well as by the RNA community of the Vienna BioCenter.
Transformation Reactions of Organic Contaminants and Oxygen: From Field Sites to Reaction Mechanisms
Title to be announced
Multiscale plant bioimaging using advanced microscopy
Parthenogenesis, cryptobiosis, and the survival in extreme environmental conditions
Evading ageing: Mitochondrial and proteostatic adaptations in oocytes
Genomes in Rhodnius prolixus symbiotic system
Stem cells, immune evasion and metastasis in colorectal cancer
Ubiquitin & Friends Symposium 2024
The Ubiquitin & Friends Symposium is an annual international meeting taking place in the beautiful capital of Austria, aiming to bring together scholars from various fields studying ubiquitin/Ubl biology and protein degradation in a personal, family-like atmosphere, as suggested by the name.
The evolution and development of mollusc shells
Unraveling the Complexity of Crossover Regulation in C. elegans
Dynamics of 3D Genome Structure and Function
How superworms can help to solve our plastic waste crisis
New players in an old pathway: biology of methanogens of the TACK superphylum
Shaping morphogen gradients: from molecules to tissues and back
Studying stressed cells by in situ structural biology
Exploring Microbial Resilience: Unravelling Escherichia coliand#x27;s Stress Response at the Level of Protein Synthesis
Arbuscular mycorrhiza development and function
Deep homology and deep diversity: Evolving genetic toolkits for making and sensing light
The evolution of cell type identity and tissue microecology at the fetal-maternal interface
The unanticipated roles of PICIs and phages in bacterial evolution
Chemical targeting of subcellular protein localization
Origin and diversification of gut-derived organs in chordates
Job's Dilemma for the Genome: Why Bad Things Happen to Good Chromosomes
Connections between carbon and nitrogen cycling in the ocean
Understanding how the DNA-loop-extruding protein complex Condensin folds a chromatinized genome into mitotic chromosomes
From Roads to Rivers? Occurrence and environmental fate of tire and road wear particles and of tire-related chemicals
FENS 2024 Satellite event: Home cage behavior monitoring at the interface of animal welfare and neuroscience
Striking physiology and cell biology of (marine) environmental microorganisms
Mechanisms controlling maintenance of cohesin dependent loops
Title to be announced