SLAC's SSRL synchrotron aids in discovery of new antibiotic

To advance the fight against antibiotic resistance, a team led by James Fraser, professor at UCSF School of Pharmacy and #BioMBIB faculty scientist, has developed a compound that could help restore the effectiveness of a class of antibiotics known as streptogramins. They were able to see how this compound inhibited the pivotal protein that reduced the power of streptogramins through structures solved with data collected at beamline 8.3.1 at Berkeley Lab's Advanced Light Source, run by James Holton, #BioMBIB faculty scientist, and the Stanford Synchrotron Radiation Lightsource. Optimizing this compound could lead to a therapeutic option in cases where these and other classes of antibiotics were previously ineffective.

𝗔 𝗙𝗼𝘂𝗻𝗱𝗮𝘁𝗶𝗼𝗻𝗮𝗹 𝗕𝗿𝗲𝗮𝗸𝘁𝗵𝗿𝗼𝘂𝗴𝗵 𝗚𝘂𝗶𝗱𝗶𝗻𝗴 𝗩𝗶𝗮𝗰𝘂𝗿𝗲‘s 𝗠𝗶𝘀𝘀𝗶𝗼𝗻! 🚀 🔬 A landmark study published in Nature by our CSO, Dr. Heiko Lickert, unveiled the critical role of 𝗶𝗻𝗰𝗲𝗽𝘁𝗼𝗿, a novel inhibitor of insulin signaling in pancreatic β-cells. The study showed that in vivo genetic ablation of inceptor function significantly increases β-cell insulin sensitivity, proliferation, survival, and function, leading to improved glucose tolerance. This wasn't just a discovery; it was the identification and validation of a completely novel drug target for β-cell protection and regeneration for a causal therapy of diabetes. At 𝗩𝗶𝗮𝗰𝘂𝗿𝗲, we are building directly upon this breakthrough discovery. We are actively leveraging on deep mechanistic understanding of β-cell biology to develop innovative treatments aimed at sensitizing β-cells to insulin, offering a new drug intervention point to prevent β-cell failure and revolutionize diabetes care. 👉 If you want to delve deeper into this groundbreaking research, read the original paper here: https://lnkd.in/e54cRgw

Researchers developed CloneSeq-SV, a novel approach to study drug resistance in HGSOC. Analyzing 18 patients over a multi-year period, they found that: - Drug resistance arises from selective expansion of a single or small subset of clones present at diagnosis - Drug-resistant clones exhibit distinctive genomic features, such as chromothripsis and oncogene amplifications - Pre-existing transcriptional states, like epithelial-to-mesenchymal transition, are linked to drug resistance These findings suggest that drug-resistant states pre-exist at diagnosis, leading to reduced clonal complexity at relapse. This research motivates investigation of evolution-informed adaptive treatment regimens to combat drug resistance in HGSOC. https://lnkd.in/ezRtay7h

🧬 𝗡𝗼𝘃𝗲𝗹 𝗯𝗮𝗰𝘁𝗲𝗿𝗶𝗮𝗹 “𝗽𝗶𝗴𝗴𝘆𝗯𝗮𝗰𝗸” 𝗽𝗹𝗮𝘁𝗳𝗼𝗿𝗺 𝗳𝗼𝗿 𝗮𝗻𝘁𝗶𝗯𝗼𝗱𝘆 𝗽𝗿𝗼𝗱𝘂𝗰𝘁𝗶𝗼𝗻 A recent study from Imperial College London presents citrOgen, a synthesis-free platform that produces and presents bacterial polysaccharide and protein antigens naturally using 𝘊𝘪𝘵𝘳𝘰𝘣𝘢𝘤𝘵𝘦𝘳 𝘳𝘰𝘥𝘦𝘯𝘵𝘪𝘶𝘮. The researchers expressed antigens from two WHO critical priority pathogens and generated specific IgG antibodies which proved functional in protection studies, capsular serotyping, and biofilm inhibition. Full paper: https://lnkd.in/eSxmft2M #Biointron #AntibodyDiscovery #DrugDiscovery #Immunotherapy Study by Joshua L C Wong, Julia Sánchez-Garrido, Jaie Rattle, Jonathan Bradshaw, Vishwas Mishra, PhD & Gad Frankel

I’m excited to share that our review article, “Tellurium nanoparticles as antimicrobial agents for multi-drug-resistant infections” (RSC Advances, 2025) is now published and open access! 🎉 🔗 Read it here; https://lnkd.in/eYZgq-Bf In this work, we explore the potential of tellurium nanoparticles (TeNPs) to combat the rising global challenge of antimicrobial resistance. Some highlights: TeNPs employ multiple mechanisms, from membrane disruption to ROS generation, DNA/RNA damage, and enzyme inhibition, making it harder for pathogens to develop resistance. They show promise in disrupting biofilms, a major barrier in chronic infections. We also discuss the synergy between TeNPs and conventional antibiotics, which may enable lower drug doses and mitigate side effects. Critical challenges remain around biocompatibility, scalability, and safety, which we address in the roadmap toward clinical translation. I’m thankful for the collaboration of a multidisciplinary team that made this possible. I hope this article contributes meaningfully to the search for novel antimicrobial strategies. If you work in antimicrobial research, nanomedicine, or related fields: I’d love to hear your thoughts, whether on applications, challenges, or future directions. Let’s connect. #AntimicrobialResistance #Nanotechnology #TelluriumNanoparticles #BiomedicalResearch #OpenAccess #Nanomedicine

📈 PKpredict: A Computational Tool to Predict Tuberculosis Drug Penetration At CIBB 2025, Roberto Visintainer presented PKpredict, a framework developed with the Gates Medical Research Institute. The tool combines machine learning with pharmacokinetic modeling to predict how anti-TB drugs penetrate lung lesions and caseum — a key factor for treatment success. By training on data from 30 compounds in rabbit models, PKpredict supports faster drug discovery and the prioritization of more effective therapies. 👉 Learn more about COSBI's projects: https://lnkd.in/d-HWYY94

🧬 GPCRs are a hot topic and one of the most targeted protein families in drug discovery, but unlocking their structural secrets is a real challenge.   At Novalix, in collaboration with LSMBO, we’ve just published a breakthrough study in Scientific Reports on GPBAR1, a GPCR involved in metabolic regulation and inflammation. Using cryo-EM (2.5 Å), HDX-MS (>75% sequence coverage), and mass photometry, we revealed the molecular dynamics of GPBAR1–Gs protein interactions, a key step toward targeting metabolic disorders.   🔬 This HDX-MS study is one of the few performed on a fully active full-size GPCR.   👉 Read the full article here: https://lnkd.in/eBrKjdVN   Because understanding how these proteins behave at the molecular level opens the door to better guided drug design, especially for GPCRs.   💬 If you are working on membrane protein and you are facing these challenges, let’s talk.   #CryoEM #GPCRs #DrugDiscovery #MS #Biophysics

First-authored research article no 5. A new finding in adjuvant technology. Adjuvants have been used for seven decades, having several side effects, especially inflammation. Instead, we offer the use of free metal ions to improve the efficacy of vaccine modalities. We proved that trace amounts of cobalt (5 μM) can significantly increase the enhancement of immune potentials of two vaccine types, inactivated and subunit vaccine candidates. The concentration we used here is far below the acute toxic threshold and safe from risk-benefit analysis. For further details, you may have a look at our newly published research article. https://lnkd.in/g6xdP8UQ

The Progress of Research on Oligonucleotide Conjugates Oligonucleotides, such as antisense oligonucleotides, small interfering RNA (siRNA), aptamers, etc., can achieve the purpose of treating diseases by targeting pathogenic RNA or proteins and inhibiting their activity. However, many types of oligonucleotides have shortcomings such as poor active targeting, instability in vivo, and poor transmembrane ability. Therefore, researchers usually improve the functions and properties of nucleic acid molecules based on traditional oligonucleotides by covalent conjugation with other functional molecules, such as cell uptake, tissue delivery efficiency, bioavailability, catalytic effect, etc., to enhance the therapeutic effect of nucleic acids. https://lnkd.in/gaf-CYzd

Single-Cell Mitochondrial DNA Analysis of Recombinant Chinese Hamster Ovary Cells Reveals Widespread Heteroplasmy Recent bulk analysis of Chinese hamster ovary (CHO) cell mitochondrial DNA revealed widespread heteroplasmy across cell lines and even within clones of the same parental host. To address this, we applied our previously developed single-cell mtDNA sequencing (scmtDNAseq) method to 84 single CHO cells. We identified widespread intercellular heteroplasmy across the CHO cell population and predicted possible phenotypic impacts. 3/11 (27%) of the most variable mutations were only identified by scmtDNAseq, indicating greater resolution when compared to bulk cell analysis. Single-cell RNAseq (scRNAseq) was also performed at the same time point and compared to scmtDNAseq, significant differences in intercellular heteroplasmy were observed. Using an inducible mAb expression system demonstrated that short-term additional biosynthetic burden of exogenous protein production had little impact on intercellular heteroplasmy. https://lnkd.in/g2AeeXrn #aspenalert #biotech #bioprocess