Check out two pre-publications available in bioRxiv, by lead-author Jacob Croft, from Kelly Lee's lab, at the University of Washington in collaboration with our Center’s Computational Biology Core scientists, Hung Do and S. Gnanakaran from Gnana's lab at Los Alamos National Laboratory. Croft et al. used cryo-electron tomography and sub-tomogram averaging of HIV-1 virus-like particles (VLPs), Hydrogen/Deuterium-Exchange Mass Spectrometry and Molecular Dynamics to capture the structural dynamics of HIV-1 Env proteins in the context of the cell membrane. They identified critical interactions and Env structural rearrangements providing insight to essential roles the membrane plays in presenting the Envs in its native conformation on the virion surface and dig deeper in a follow-up paper, revealing critical interactions inside the cell, between the Env cytoplasmic tail and matrix domain of Gag polyprotein, required for Env assembly, presentation, clustering, receptor binding and membrane fusion, all essential for viral propagation. These exciting results reveal the power of these synergistic approaches and the importance of studying Env structures in the context of a membrane. Inside the cell, Gag polyproteins ,recruited to the inner leaflet, help package and present the Env on the outside cell surface. The cell now poised to infect new cells while, simultaneously, exposing the Env to an unrelenting barrage of antibodies seeking to neutralize further infection. Paper #1 https://lnkd.in/eizZwbJF Follow-up Paper https://lnkd.in/exxQxax9
HIV-1 Env protein dynamics in cell membrane studied by Croft et al.
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Spatial biology is moving beyond counting transcripts - toward understanding function, diversity, and cellular identity in context. Over the past two years, we’ve developed Direct-Seq, a spatial transcriptomics approach built on the #G4X platform that enables in situ sequencing of highly variable immune receptor regions at single-cell resolution in intact tissue. This unlocks spatial mapping of IgH and TCRβ clonotypes in both fresh-frozen and FFPE samples - fully compatible with multiplex protein staining - bringing immune repertoire profiling directly into tissue microenvironments. To further expand performance in FFPE tissues, we developed a Direct-Seq v2 chemistry that significantly improves sensitivity across larger RNA regions, achieving the detection sensitivity closer to direct transcript counting. Our team will be presenting this work at #AGBT2026 and sharing how spatial immune repertoire sequencing may help expand multiomic insights in tissue biology.
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Decoding RNA microenvironments at subcompartmental resolution In our new NAR Nucleic Acids Research paper, spearheaded by fantastic PhD student Anja Trupej, we introduce HCR-Proxy, a modular proximity labeling approach for profiling the local proteome composition around RNA at nanoscale, subcompartmental resolution. Using it, we resolved nested nucleolar layers and uncovered the molecular grammar governing spatial protein partitioning within RNA-rich condensates. Link to the paper: https://lnkd.in/dhjUaPTa
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Excited to share our latest research, "Deciphering hydration patterns across RNA conformations: Insights into recognition mechanisms," where we explore a fundamental yet often overlooked aspect of structural biology, the role of hydration in RNA adaptability. We utilized all-atom molecular dynamics simulations to map how water molecules interact with different RNA conformations, showing that hydration landscapes actively dictate recognition pathways. You can read the full paper here: https://lnkd.in/erSSms8A #ComputationalChemistry #StructuralBiology #RNA
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LCGC International A spatially resolved proteomics workflow was established by combining nanosecond mid-infrared laser layer-by-layer ablation of human corneal tissue with liquid chromatography–tandem mass spectrometry (LC–MS/MS). The approach provided insights into metabolic activity, immune function, and wound-healing processes within individual corneal layers, demonstrating the power of LC–MS/MS-based chromatography for elucidating corneal biology, disease mechanisms, and potential pharmacological targets. https://lnkd.in/ezAay8DV
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I will be presenting our recent work on the interplay between disordered regions, folded domains, and RNA at the Biophysical Society Annual Meeting in San Francisco. If you are around, you are welcome to stop by. Together with Ayush Gupta and Karim Malekzadeh, we investigated how specific interactions could promote structural stability and help avoid aggregation. You can find me below: 1️⃣ Modulation of FUS RRM Folding by the Neighboring Disordered Region 📅 Monday, February 23 | 1:45–3:45 PM | Exhibit Halls ABC | Board B106 Poster Session: Intrinsically Disordered Proteins II 2️⃣ Synergistic Role of RGG2 in Modulating FUS RRM Structure and RNA Binding Revealed by Enhanced Sampling Simulations 📅 February 25 | 10:30 AM–12:30 PM | Exhibit Halls ABC | Board B104 Poster Session: Protein–Nucleic Acid Interaction II Additional presentations: • SRAA Poster Competition — Sunday, February 22 | 6:00–9:00 PM | Exhibit Hall ABC | Board S61 • Just-B Poster Session — Monday, February 23 | 4:00–5:00 PM | Exhibit Hall ABC | Board B39 #GHZlab #BiophysicalSociety #ComputationalBiology #MolecularDynamics #EnhancedSampling
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Antiphospholipid syndrome is different for every patient, so why isn't treatment individualized to a patient's underlying biology? Using RNA sequencing and machine learning, U-M Health's Ray Zuo, M.D., M.S., and team have identified four distinct clusters in APS patients that can begin the process of tailoring care based on patient biology. Read more about these distinct clusters and the next steps at individualizing treatment using the link from the Health Lab Blog. https://michmed.org/rwqzd
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See the latest research from Dr. Ray Zuo, assistant professor in the Division of Rheumatology, and his U-M colleagues, which uses unsupervised machine learning to uncover why antiphospholipid syndrome (APS) presents differently from one patient to another. Read more using the link below ⬇️
Antiphospholipid syndrome is different for every patient, so why isn't treatment individualized to a patient's underlying biology? Using RNA sequencing and machine learning, U-M Health's Ray Zuo, M.D., M.S., and team have identified four distinct clusters in APS patients that can begin the process of tailoring care based on patient biology. Read more about these distinct clusters and the next steps at individualizing treatment using the link from the Health Lab Blog. https://michmed.org/rwqzd
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How does cholera colonize the gut? 🦠 Researchers from IRB Barcelona, IBMB, EMBL Heidelberg and the University of Detroit Mercy have used cryo-electron microscopy to provide an answer. “Understanding this interaction at the molecular level gives us a new way to think about how bacterial virulence is controlled,” commented lead author Miquel Coll. >>> https://lnkd.in/esVwcNnC
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Happy to share our recently published paper in Plasmonics (Springer Nature)! 🎉 *📄 Photonic Crystal Fiber Plasmonic Biosensor for SARS-CoV-2 Particle Quantification and Detection* As the third author, I contributed to the methodology, simulations, and data analysis. This work presents a compact PCF-based plasmonic biosensor with high sensitivity for detecting SARS-CoV-2 RNA, spike proteins, and antibodies, highlighting its potential for point-of-care diagnostics. Grateful to collaborate with a great team on this research! *🔗 Paper link:*https://lnkd.in/gRyDGCub *#Research #Photonics #Plasmonics #Biosensors #COVID19 #AcademicResearch #SpringerNature*
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A clinical trial deadline was approaching. The patient stratification strategy wasn't ready. 🔊 "We'd been stitching imaging and omics together quite manually for months. Sonrai helped streamline the whole process, and we had stratification-ready insights in just a few days. It changed how we planned the trial." 🔊 "The ability to integrate and analyze complex molecular profiles from different sample sources was invaluable - particularly combining transcriptomics and proteomics for comprehensive insights." This is what patient stratification should look like. Not months of manual data wrangling before a trial. Clear biological understanding of your patient population, before you commit. 👉Read the case study: https://lnkd.in/eWY4V5SA
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