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Journal: Cell

Abbreviation

Cell

Publisher

Cell Press

Journal Volumes

ISSN

0092-8674
1097-4172

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Publications 1 - 10 of 158
  • The Schizosaccharomyces pombe EB1 homolog Mal3p binds and stabilizes the microtubule lattice seam
    Item type: Journal Article
    Sandblad, Linda; Busch, Karl Emanuel; Tittmann, Peter; et al. (2006)
    Cell
  • Deficiency of FANCD2-Associated Nuclease KIAA1018/FAN1 Sensitizes Cells to Interstrand Crosslinking Agents
    Item type: Journal Article
    Kratz, Katja; Schöpf, Barbara; Kaden, Svenja; et al. (2010)
    Cell
  • A generative deep learning approach to de novo antibiotic design
    Item type: Journal Article
    Krishnan, Aarti; Anahtar, Melis N.; Valeri, Jacqueline A.; et al. (2025)
    Cell
    The antimicrobial resistance crisis necessitates structurally distinct antibiotics. While deep learning approaches can identify antibacterial compounds from existing libraries, structural novelty remains limited. Here, we developed a generative artificial intelligence framework for designing de novo antibiotics through two approaches: a fragment-based method to comprehensively screen >107 chemical fragments in silico against Neisseria gonorrhoeae or Staphylococcus aureus, subsequently expanding promising fragments, and an unconstrained de novo compound generation, each using genetic algorithms and variational autoencoders. Of 24 synthesized compounds, seven demonstrated selective antibacterial activity. Two lead compounds exhibited bactericidal efficacy against multidrug-resistant isolates with distinct mechanisms of action and reduced bacterial burden in vivo in mouse models of N. gonorrhoeae vaginal infection and methicillin-resistant S. aureus skin infection. We further validated structural analogs for both compound classes as antibacterial. Our approach enables the generative deep-learning-guided design of de novo antibiotics, providing a platform for mapping uncharted regions of chemical space.
  • HLA-DR15 Molecules Jointly Shape an Autoreactive T Cell Repertoire in Multiple Sclerosis
    Item type: Journal Article
    Wang, Jian; Jelcic, Ivan; Mühlenbruch, Lena; et al. (2020)
    Cell
    The HLA-DR15 haplotype is the strongest genetic risk factor for multiple sclerosis (MS), but our understanding of how it contributes to MS is limited. Because autoreactive CD4+ T cells and B cells as antigen-presenting cells are involved in MS pathogenesis, we characterized the immunopeptidomes of the two HLA-DR15 allomorphs DR2a and DR2b of human primary B cells and monocytes, thymus, and MS brain tissue. Self-peptides from HLA-DR molecules, particularly from DR2a and DR2b themselves, are abundant on B cells and thymic antigen-presenting cells. Furthermore, we identified autoreactive CD4+ T cell clones that can cross-react with HLA-DR-derived self-peptides (HLA-DR-SPs), peptides from MS-associated foreign agents (Epstein-Barr virus and Akkermansia muciniphila), and autoantigens presented by DR2a and DR2b. Thus, both HLA-DR15 allomorphs jointly shape an autoreactive T cell repertoire by serving as antigen-presenting structures and epitope sources and by presenting the same foreign peptides and autoantigens to autoreactive CD4+ T cells in MS.
  • An Unbiased Screen for Human Cytomegalovirus Identifies Neuropilin-2 as a Central Viral Receptor
    Item type: Journal Article
    Martinez-Martin, Nadia; Marcandalli, Jessica; Huang, Christine S.; et al. (2018)
    Cell
  • Thermotolerance requires refolding of aggregated proteins by substrate translocation through the central pore of ClpB
    Item type: Journal Article
    Weibezahn, Jimena; Tessarz, Peter; Schlieker, Christian; et al. (2004)
    Cell
  • Structure and Function Analysis of an Antibody Recognizing All Influenza A Subtypes
    Item type: Journal Article
    Kallewaard, Nicole L.; Corti, Davide; Collins, Patrick J.; et al. (2016)
    Cell
    Influenza virus remains a threat because of its ability to evade vaccine-induced immune responses due to antigenic drift. Here, we describe the isolation, evolution, and structure of a broad-spectrum human monoclonal antibody (mAb), MEDI8852, effectively reacting with all influenza A hemagglutinin (HA) subtypes. MEDI8852 uses the heavy-chain VH6-1 gene and has higher potency and breadth when compared to other anti-stem antibodies. MEDI8852 is effective in mice and ferrets with a therapeutic window superior to that of oseltamivir. Crystallographic analysis of Fab alone or in complex with H5 or H7 HA proteins reveals that MEDI8852 binds through a coordinated movement of CDRs to a highly conserved epitope encompassing a hydrophobic groove in the fusion domain and a large portion of the fusion peptide, distinguishing it from other structurally characterized cross-reactive antibodies. The unprecedented breadth and potency of neutralization by MEDI8852 support its development as immunotherapy for influenza virus-infected humans.
  • SnapShot: The Nuclear Envelope II
    Item type: Other Journal Item
    Rothballer, Andrea; Kutay, Ulrike (2012)
    Cell
  • Gene Expression Changes and Community Turnover Differentially Shape the Global Ocean Metatranscriptome
    Item type: Journal Article
    Salazar Guiral, Guillem; Paoli, Lucas Pierre Antoine; Alberti, Adriana; et al. (2019)
    Cell
    Ocean microbial communities strongly influence the biogeochemistry, food webs, and climate of our planet. Despite recent advances in understanding their taxonomic and genomic compositions, little is known about how their transcriptomes vary globally. Here, we present a dataset of 187 metatranscriptomes and 370 metagenomes from 126 globally distributed sampling stations and establish a resource of 47 million genes to study community-level transcriptomes across depth layers from pole-to-pole. We examine gene expression changes and community turnover as the underlying mechanisms shaping community transcriptomes along these axes of environmental variation and show how their individual contributions differ for multiple biogeochemically relevant processes. Furthermore, we find the relative contribution of gene expression changes to be significantly lower in polar than in non-polar waters and hypothesize that in polar regions, alterations in community activity in response to ocean warming will be driven more strongly by changes in organismal composition than by gene regulatory mechanisms.
  • L-Arginine Modulates T Cell Metabolism and Enhances Survival and Anti-tumor Activity
    Item type: Journal Article
    Geiger, Roger; Rieckmann, Jan C.; Wolf, Tobias; et al. (2016)
    Cell
    Metabolic activity is intimately linked to T cell fate and function. Using high-resolution mass spectrometry, we generated dynamic metabolome and proteome profiles of human primary naive T cells following activation. We discovered critical changes in the arginine metabolism that led to a drop in intracellular L-arginine concentration. Elevating L-arginine levels induced global metabolic changes including a shift from glycolysis to oxidative phosphorylation in activated T cells and promoted the generation of central memory-like cells endowed with higher survival capacity and, in a mouse model, anti-tumor activity. Proteome-wide probing of structural alterations, validated by the analysis of knockout T cell clones, identified three transcriptional regulators (BAZ1B, PSIP1, and TSN) that sensed L-arginine levels and promoted T cell survival. Thus, intracellular L-arginine concentrations directly impact the metabolic fitness and survival capacity of T cells that are crucial for anti-tumor responses.
Publications 1 - 10 of 158