Bacterial culture collections are essential resources for exploring the diversity of microorganisms and their interactions with each other and their hosts. Here, we report on the sequencing of the first 129 bacterial isolates, representing 34 genera, from a culture collection of more than 600 bacterial strains originally isolated from leaves of a naturalised Arabidopsis thaliana […]
Widespread Epistasis between Cancer Driver Mutations and Allele-Specific Copy Number Variations
Cancer driver mutations alone are often insufficient to fully explain tumorigenesis. We demonstrate that these mutations cooperate with somatic copy number variations (CNVs) in a tissue-specific pattern of genomic epistasis. Analyzing 93,462 tumors, we identified 54 gene-cancer type pairs with significant co-occurrence of somatic mutations and CNVs. Our new Binoculars algorithm, which resolved phased DNA/RNA […]
Identification of first-in-class small molecule potential inhibitor of GDF15
Background Growth Differentiation Factor 15 (GDF15), a mitokine implicated in stress response, has been associated with numerous diseases, particularly cancer cachexia. Many approaches, including monoclonal antibodies and peptide antagonists, have been implemented to inhibit GDF15 activity. It is currently unknown whether it is possible to inhibit GDF15 using small organic molecules (SOMs). Methods A structure-based […]
Are frameworks independent from CDRs in antibodies? Exploring CDR-framework correlation networks of antibodies
The growing success of monoclonal antibodies (mAbs) in therapies highlights the importance of the humanization process in antibody design. This key step involves grafting selected complementarity-determining regions (CDRs) onto human frameworks (FWs) to reduce immunogenicity. However, the effect of this process on the antibody’s structure and dynamics is underexplored. This study uses molecular dynamics simulations […]
Ribosomal Epistatic Interactions Drive the Emergence of High-Level Streptomycin Resistance in Escherichia coli
The widespread use of antibiotics has raised serious concerns about the emergence and dissemination of antibiotic resistance in the environment. Studies reveal that environmental exposures to antibiotics and other non-antibiotic pollutants can promote the development of high-level antibiotic resistance via de novo mutations. However, specific genotypes conferring strong resistance in resistant mutants, particularly the roles […]
PD-L2 Regulates Natural Antibody and IL-10 Secretion by B-1 cells
B-1 cells are innate-like lymphocytes that play a critical role in homeostasis by secreting natural antibodies, typically IgM, and immunosuppressive molecules such as IL-10. However, the regulation of these processes in B-1 cells remains poorly understood. Here, we demonstrate that PD-L2, a surface receptor expressed by all B-1 cells, regulates B-1 cell effector functions. We […]
evo3D: a generalised framework for structure-informed evolutionary analysis, implemented in R
Selection pressures often act at the level of protein structure, yet most evolutionary analyses remain confined to linear sequences. Early structure-informed approaches improved interpretation by mapping single-site metrics onto protein structures, and later methods introduced 3D sliding windows to capture spatial neighbourhoods missed by linear analyses. These frameworks, however, are restricted to predefined statistics and […]
Regioisomer-controlled red-shifted DNA probes for imaging of living tissues
Fluorescence imaging of chromatin DNA with high resolution and specificity is key to understanding cellular processes and enabling molecular diagnostics. However, choosing the best DNA probe for in vivo imaging is often a challenging task, as systematic studies investigating the biocompatibility of these molecules are lacking. Red-shifted fluorescent probes are particularly advantageous for imaging thick […]
Uncovering the link between ATP synthase and the TCA cycle by crosslinking mass spectrometry
Mitochondrial oxidative phosphorylation (OXPHOS) comprises a series of multi-subunit protein complexes that operate in coordination with the tricarboxylic acid (TCA) cycle to generate ATP. Although these systems are metabolically interconnected, complex II is generally regarded as the only direct structural link between the OXPHOS and TCA cycle. Here, we combine in-solution crosslinking mass-spectrometry (XL-MS), quantitative […]
Environment and physiology shape antiphage system expression
Bacteria and archaea encode on average ten antiphage systems. Quorum sensing, cellular, or transcription factors can regulate specific systems (CRISPR-Cas, CBASS). Yet, a systematic assessment of antiphage systems expression patterns is lacking. Here, we combine publicly available RNA-seq data from 14 different species with an original RNA-seq dataset of 15 Escherichia coli strains across six […]