TowardPi’s Post

Scientists at Sanford Burnham Prebys have found that small extracellular vesicles (sEVs) traveling between Christine S. Liu the brain carry more complete instructions for altering cellular function than previously thought. Main Takeaways: 🪩 Neural sEVs contain full-length poly-adenylated mRNAs with diverse and novel isoforms. 🪩 Neural sEV mRNA composition is distinct from bulk brain and includes L1Hs sequences. 🪩 Neural sEVs are selectively packaged by Alzheimer’s disease state and cell type. 🪩 Neural sEV-enriched mRNAs contain RNA-binding protein motifs Congratulations to Linnea Ransom, Christine S. Liu, Emily Dunsmore, Carter Palmer, Juliet Nicodemus, Derya Degirmenci Ziomek, Nyssa Williams, and Jerold Chun! Their work can be accessed here: https://lnkd.in/e5Q3GBVb #nanoparticles #exosomes #vesicles #mRNA #RNA #innovation #research #education #pharma #science #biology #molecularbiology

✨ Excited to share our latest publication in Nature Communications! This is my second coauthored paper in Nature Communications! 🎉 The study, "Vasculogenic skin reprogramming requires TET-mediated gene demethylation in fibroblasts for rescuing impaired perfusion in diabetes," investigates innovative strategies for improving vascular repair in diabetes. You can read the full article here: https://lnkd.in/gRH6wdeq. A special congratulations to the first authors, Dr. Sujit K. Mohanty and Dr. Kanhaiya Singh, and to Dr. Chandan K. Sen, the PI and mentor leading this work, for their outstanding vision and dedication. I’m proud to have contributed, among others, to this work by conducting single-cell RNA sequencing experiments for 7 samples using the 10x Chromium device, including GEM production, cDNA synthesis, DNA cleaning, library construction, and cDNA/library quality checks, in the Indiana University ICRME (Indiana Center for Regenerative Medicine and Engineering), which is part of the Department of Surgery, where I started my single-cell RNA sequencing adventure. 🔬 Transitioning from hands-on single-cell experiments to 💻 bioinformatics codes, functions, and algorithms, I’ve learned how to connect the 🧬 cells I see under a microscope to the numbers and patterns revealed through data analysis. This dual perspective has allowed me to understand and approach problems from both sides, bridging experimental and computational biology. #NatureCommunications #SingleCellRNAseq #10xGenomics #Bioinformatics #DiabetesResearch #RegenerativeMedicine #Collaboration #CellChat #UMAP #DotPlot #VlnPlot

https://lnkd.in/eD59nwt8 I'm excited to share the main chapter of my PhD dissertation, now published in Genes!  For the first time, we investigated how transfer RNA levels are fine-tuned during brain development in fruit fly ( Drosophila) - neurobiology's favorite model organism. Key finding: Neural stem cells and neurons maintain different tRNA expression profiles to optimize the production of cell-type specific proteins. Using transcriptome-wide "omics" approaches - hydro-tRNAseq, (m)RNAseq, cell-type specific mRNA decay measurements - our model supports that differential tRNA abundance during Drosophila neurogenesis likely serves to shift optimal translation from proliferation toward a subset of differentiation associated transcripts (especially RNA-binding proteins and kinases). Intriguingly, we didn't observe any widespread 'anticodon buffering' in the Drosophila nervous system as compared to previous reports in the mammalian CNS - where changes in individual tRNA genes don't affect the overall anticodon pool. We think this difference reflects the shorter timescale of invertebrate neurogenesis compared to mammals, creating selection pressure to evolve quick-acting post-transcriptional regulatory mechanisms such as unbuffered tRNA changes to modulate translation of existing mRNAs. Grateful to my PhD advisors Michael Cleary and David Ardell. Special thanks to my former Cleary Lab mate Josephine Sami, PhD for generating the mRNA decay data.

Organoids offer potential for applications such as developmental biology research, drug screening, and companion diagnostics. However, capturing high-resolution images of living organoids without pre-treatment, like staining or fixation, has been a challenge. We recently published a paper showcasing high-resolution, label-free imaging and analysis of live intestinal organoids using holotomography. This work was made possible through a collaboration between the IBS team led by Director Koo Bon-kyung, organoid culturing expertise, TOMOCUBE, INC.’s the 2nd generation holotomography HT-X1 and software development, and measurement and analysis by Dr. Manjae Lee's Biomedical Optics Lab at KAIST. You can read more in the paper here: https://lnkd.in/g36-BNU4 While we’ve made progress, new challenges have emerged. For organoids thicker than 150 µm, blurring caused by multiple scattering becomes an issue. Overcoming this will allow us to apply holotomography to larger organoids. Additionally, the ability to analyze cell types and states directly from holotomography images would be a new research direction. Exciting times ahead for organoid research! #Organoids #Holotomography #BiomedicalInnovation #DrugScreening #LifeScience #Tomocube #KAIST #IBS

🌟 Exciting Advances in Sonogenetics and Sonopharmacology! 🌟 It started in 2021 with the first publication in #NatureChemistry and since then a lot has happened around the fields of #Sonopharmacology and #Sonogenetics at DWI... In their recent publication in the journal #AdvancedAdvanced Materials, Aman Ishaqat, Johannes Hahmann, Cheng Lin, Xiaofeng Zhang, Chuanjiang He, Wolfgang H. Rath, Pardes Habib, Sabri E. M. Sahnoun, Khosrow Rahimi, Rostislav Vinokur, Felix M. Mottaghy, Robert Göstl, Matthias Bartneck, and Andreas Herrmann transferred the conceptual framework of polymer mechanochemistry to in vivo applications, specifically immunostimulation, using medically approved imaging ultrasound. They also validated the sonogenetic function of their system by achieving gene knockdown in mammalian cell cultures. This proof of concept paves the way for broad therapeutic applications across various diseases. If you would like to find out more, you can find the publication (open access) here: https://lnkd.in/eEgyXhQr We also recommend the current review by Johannes Hahmann, Aman Ishaqat, @Twan Lammers and Andreas Herrmann in #AngewandteChemieInternationalEdition. The authors highlight the potential of sonogenetics – a cutting-edge technique that uses ultrasound to control and monitor cellular functions. Combining genetic engineering with ultrasound, this approach offers non-invasive and precise manipulation of cells. From imaging to therapy, sonogenetics surpasses the limitations of optogenetics and magnetogenetics, offering deep tissue penetration and high spatiotemporal control. The review can be found here (open access): https://lnkd.in/eS4df6rg We are curious to see what else is coming... This research work is funded and supported by Deutsche Forschungsgemeinschaft (DFG) - German Research Foundation, Werner Siemens-Stiftung, and Max Planck School Matter to Life, among others.

Nanobodies are emerging as state-of-the-art molecular tools for protein science. Their small size and high specificity make them versatile instruments in both structural and functional studies of proteins. The recent development of anti-Arc nanobodies has allowed us to test their potential at Petri Kursula's research group. Arc, or activity-regulated cytoskeleton-associated protein, is a complex regulator of synaptic plasticity in glutamatergic neurons. By regulating the long-term potentiation and depression of synapses, Arc coordinates the reorganization of synaptic circuits during memory and learning. Despite its relevance, its mechanisms of action are only partially understood! To validate new molecular tools to study Arc, we have collaborated with Clive Bramham to explore the practicality of anti-Arc nanobodies. We are happy to report very interesting findings! Two nanobodies, E5 and H11, can bind the peptide-binding pocket of human Arc (an important mediator of Arc function). They can also displace a high-affinity endogenous ligand of Arc, showing their potential as competitive inhibitors of Arc. In addition, both nanobodies are great crystallization chaperones. They have promoted the crystallization of the Arc N-lobe, providing us with high-resolution X-ray crystallography data! Could we use both nanobodies to modulate the function of Arc in cell studies? Could these nanobodies promote the crystallization of other recombinant constructs of Arc? The potential of anti-Arc nanobodies has just begun to be explored, and we cannot wait to find out what will be discovered next. Thank you so much to everybody who has collaborated on this study! 😊 Lasse Neset Sigurbjörn Markússon Sarah W. Oda Krokengen Aleksi Sutinen Eleni Christakou Andrea J. Lopez Clive Bramham Petri Kursula

📣 Call for Papers 📣 Deadline extended to 10/15/2024! You are invited to submit papers on Voltage-Gated Sodium Channels to be published throughout the year and highlighted in a special issue 📙 ➡️ https://hubs.la/Q02LVgKY0 Journal of General Physiology (JGP) welcomes submissions that focus on increasing our understanding of the role of voltage-gated sodium channels in the broad physiological and pathophysiological context. Topics of interest include but are not limited to, atomistic modelling, biophysics of gating, structural and biochemical investigations, computer simulations, cellular excitability, subcellular expression and regulation, sodium channels in diseases (cardiac, muscle, pain, epilepsy and any other) and mechanistic investigations of sodium channelopathies using new model systems, such as stem cell-derived cells. We also welcome studies involving patients suffering from sodium channel-related diseases. Submit your research here ➡️ https://hubs.la/Q02LVgKY0

🌟 Exciting Research Update! 🌟 Our latest study on Alzheimer’s disease (AD), a devastating neurodegenerative disorder affecting millions worldwide, has been published in Nature’s Scientific Reports. 🧠✨ In this research, we explored how static and oscillating electric fields can disrupt the harmful Aβ fibrils associated with AD. Using molecular dynamics simulations, we specifically examined a polymorphic fibrillar complex of the Aβ1–40 peptide with the Osaka mutation (E22Δ), which is known for its toxicity and stable structure. Our findings reveal that applying a 0.3–0.4 V/nm electric field at a 0.20 GHz frequency can effectively disrupt these toxic fibrils, potentially offering a novel therapeutic approach to combating AD pathology. This is a promising step forward in understanding and addressing Alzheimer’s disease. 🔬⚡ A huge thank you to Dr. Artyom Baev, Dr. Erkin Kurganov, and my dedicated MSc student Mukhriddin Makhkamov for their valuable contributions to this work. Read the full paper here: https://lnkd.in/ddSvPmmS #AlzheimersResearch #NeurodegenerativeDisorders #MolecularDynamics #Therapeutics #ScientificReports #ElectricFields #ResearchInnovation #ADPathology

🚨 Exciting Breakthrough in Cellular Biology! 🚨 A team of Czech researchers, including scientists from Institute of Molecular Genetics of the Czech Academy of Sciences, Institute of Biotechnology of the Czech Academy of Sciences, Ústav organické chemie a biochemie AV ČR, Charles University, BIOCEV - Biotechnology and Biomedicine Centre of the Academy of Sciences and Charles University, and CEITEC - Central European Institute of Technology, has uncovered the molecular mechanisms behind the protein MICAL1 - a key regulator of the cytoskeleton. Using advanced cryo-electron microscopy, they revealed how MICAL1 remains inactive until needed, preventing cellular damage. This discovery sheds light on how cells maintain their shape and flexibility, with implications for treating diseases like epilepsy linked to MICAL1 dysfunction. 🔬 Published in Nature Communications, this research is a significant step toward understanding cellular structure and developing targeted therapies. 🍾 Congratulations: Daniel Rozbesky and Matej Horvath More info: https://lnkd.in/gPy6BA4W Link to the study: Horvath, M., Schrofel, A., Kowalska, K. et al. Structural basis of MICAL autoinhibition. Nat Commun 15, 9810 (2024). https://lnkd.in/g-Anydrt

I am incredibly proud to have published my first article in the International Journal of Molecular Sciences! This achievement would not have been possible without the amazing support and collaboration of my team: Benilde JImenez Cuenca, Bárbara Acosta-Iborra, and Ana Isabel Gil Acero. Benilde and Bárbara were my mentors throughout this process, guiding and supporting me every step of the way. Together, we have explored how the transcription factor Bhlhe40 regulates proliferation and angiogenesis in mouse embryoid bodies under hypoxia. This work is crucial for understanding key adaptive responses to unbalanced oxygen tension, which is central to tissue homeostasis and disease. Our study reveals the pivotal role of Bhlhe40 as a negative regulator of blood vessel formation, opening new avenues for future research in biomedicine. I am deeply grateful for the opportunity to work with this exceptional team and to contribute to the advancement of scientific knowledge. You can read the article here: https://lnkd.in/eH-9ccgv #Science #Research #Hypoxia #Biomedicine #Publication