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Cell Systems
This journal offers authors two options (open access or subscription) to publish research

Mar 17, 2021

Volume 12Issue 3p205-288
Open Archive
On the cover: In this issue, Xiang et al. (220–234) report a strategy to systematically investigate camelid nanobody repertories. The authors map and analyse the epitopes of >100,000 antigen-nanobody complexes from immunised llamas using high-throughput structural modeling, cross-linking mass spectrometry, mutagenesis and deep learning, and provide insights into the mechanisms of antigen-nanobody binding. Image credit: Cavan Images and Getty....
On the cover: In this issue, Xiang et al. (220–234) report a strategy to systematically investigate camelid nanobody repertories. The authors map and analyse the epitopes of >100,000 antigen-nanobody complexes from immunised llamas using high-throughput structural modeling, cross-linking mass spectrometry, mutagenesis and deep learning, and provide insights into the mechanisms of antigen-nanobody binding. Image credit: Cavan Images and Getty.

Peer Review

Voices

  • How are methodological developments enabling insights into cell behavior in cellular communities?

    I think it is a cocktail of methodologies that, together, has changed the landscape of how we investigate cell behavior within cellular communities. At the top among those, in my opinion, is the broad range of genetic manipulations that are possible in vivo. Today, genome editing, transgenic, and neighbor labeling technologies allow us to visualize and independently follow multiple cell types in vivo while at the same time, silencing, mutating, or overexpressing genes with fine spatiotemporal control.

Articles

  • Quantitative measurements of early alphaviral replication dynamics in single cells reveals the basis for superinfection exclusion

    • Zakary S. Singer,
    • Pradeep M. Ambrose,
    • Tal Danino,
    • Charles M. Rice
    Singer et al. utilize quantitative single-cell and single-molecule methods to investigate the earliest events of alphaviral replication biology. Through measurements of viral kinetics at the RNA and protein levels, they reveal the trajectory of viral replication. Applying this approach in the context of viral competition reveals that the rapid kinetics of viral replication with a limited cellular carrying capacity are able to explain the long-observed phenomenon of alphaviral superinfection exclusion.
  • Integrative proteomics identifies thousands of distinct, multi-epitope, and high-affinity nanobodies

    • Yufei Xiang,
    • Zhe Sang,
    • Lirane Bitton,
    • Jianquan Xu,
    • Yang Liu,
    • Dina Schneidman-Duhovny,
    • Yi Shi
    Xiang et al. developed a strategy to systematically investigate the repertories of camelid nanobodies for antigen binding. Thousands of diverse and high-affinity Nb families have been identified and affinity-classified. The authors employed hybrid structural proteomics to map epitopes of >100,000 antigen-nanobody complexes to understand the mechanisms underlying mammalian humoral immunity.
  • A platform for experimental precision medicine: The extended BXD mouse family

    • David G. Ashbrook,
    • Danny Arends,
    • Pjotr Prins,
    • Megan K. Mulligan,
    • Suheeta Roy,
    • Evan G. Williams,
    • Cathleen M. Lutz,
    • Alicia Valenzuela,
    • Casey J. Bohl,
    • Jesse F. Ingels,
    • Melinda S. McCarty,
    • Arthur G. Centeno,
    • Reinmar Hager,
    • Johan Auwerx,
    • Lu Lu,
    • Robert W. Williams
    Ashbrook et al., have expanded the BXD family to 140 strains, providing a new tool for translational precision and predictive biology, and extended the usefulness of the deep phenome of >100 omics datasets and >7,500 classical phenotypes already available. They show increased precision and power by using new genotypes, updated models, and more strains.
  • TAMEP are brain tumor parenchymal cells controlling neoplastic angiogenesis and progression

    • Roland E. Kälin,
    • Linzhi Cai,
    • Yuping Li,
    • Dongxu Zhao,
    • Huabin Zhang,
    • Jiying Cheng,
    • Wenlong Zhang,
    • Yingxi Wu,
    • Katharina Eisenhut,
    • Philipp Janssen,
    • Lukas Schmitt,
    • Wolfgang Enard,
    • Friederike Michels,
    • Charlotte Flüh,
    • Mengzhuo Hou,
    • Sabrina V. Kirchleitner,
    • Sebastian Siller,
    • Matthias Schiemann,
    • Immanuel Andrä,
    • Eloi Montanez,
    • Claudio Giachino,
    • Verdon Taylor,
    • Michael Synowitz,
    • Jörg-Christian Tonn,
    • Louisa von Baumgarten,
    • Christian Schulz,
    • Ines Hellmann,
    • Rainer Glass
    The rapid expansion of aggressive brain tumors is supported by the tumor parenchyma including blood vessels and myeloid cells (CNS- or bone-marrow-derived macrophages). Our study reveals TAMEP as a cell subset in the brain tumor microenvironment, which is generated by progenitor cells in the CNS. TAMEP have a myeloid appearance but do not originate from CNS or peripheral macrophages. TAMEP strongly support pathological angiogenesis and promote brain tumor growth.
  • Circumventing neural damage in a C. elegans chemosensory circuit using genetically engineered synapses

    • Ithai Rabinowitch,
    • Bishal Upadhyaya,
    • Aaradhya Pant,
    • Dolev Galski,
    • Lena Kreines,
    • Jihong Bai
    Neuronal loss due to injury or disease could lead to considerable impairments. We asked whether such conditions could be alleviated by genetically inserting new synaptic connections into the damaged neural circuit, providing alternative pathways for information flow. We focused on the relatively simple and extensively studied olfactory circuit of the tiny nematode worm, C. elegans. Loss of a single pair of interneurons in this circuit diminished chemosensory performance. We designed a synaptic bypass, implemented by genetically inserting an electrical synapse into the circuit, which restored behavioral performance. We further found that the impact of the synthetic connection was also due to the amplification of weakened sensory signals in the damaged circuit, enabled by the formation of new lateral left-right electrical connections. Our findings demonstrate the power of engineered electrical synapses as a tool for analyzing neural circuit structure-function relations and as a potential strategy for the repair of damaged neural circuits.
  • Ultrasensitive molecular controllers for quasi-integral feedback

    • Christian Cuba Samaniego,
    • Elisa Franco
    Molecular feedback loops enable adaptive and dynamic behaviors in biology. Through computations and theory, we show that ultrasensitive motifs with a tunable threshold can operate as robust feedback controllers, and we suggest specific routes for practical implementation.
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