Article
Chemistry, Multidisciplinary
Leonie Schneider, Kersten S. Rabe, Carmen M. Dominguez, Christof M. Niemeyer
Summary: This study utilizes DNA nanostructures to create multivalent artificial antigens and investigates the spatial requirements and critical factors for mast cell activation. It reveals the importance of antigen-directed assembly of antibody-receptor complexes in triggering degranulation.
Article
Chemistry, Multidisciplinary
Leonie Schneider, Kersten S. Rabe, Carmen M. Dominguez, Christof M. Niemeyer
Summary: The immunological response of mast cells is regulated by the binding of antigens to IgE antibodies bound to the Fc epsilon RI receptor on the cell membrane surface. However, the organization and structural requirements of these antigen-antibody-receptor complexes at the nanometer scale are not fully understood. In this study, DNA nanostructures were used to generate multivalent artificial antigens, allowing for control over valency and nanoscale architecture. The results showed that the assembly of antibody-receptor complexes is critical for mast cell activation, and the affinity and nanoscale distance between the binding partners have less influence on the activation process.
Article
Multidisciplinary Sciences
Joseph R. R. Egan, Enas Abu-Shah, Omer Dushek, Tim Elliott, Ben D. D. MacArthur
Summary: The interaction between T cell receptors (TCRs) and peptide major histocompatibility complex (pMHC) ligands on T cells and antigen presenting cells (APCs) is often stochastic. This study reveals that the information imparted to T cells during this interaction, assessed by the entropy rate of TCR-pMHC binding dynamics, is more important than the strength of binding itself in eliciting an immune response. Optimizing the inherent stochasticity of TCR-pMHC binding dynamics may enhance effective T cell therapeutics.
JOURNAL OF THE ROYAL SOCIETY INTERFACE
(2022)
Article
Chemistry, Multidisciplinary
Joschka Hellmeier, Rene Platzer, Vanessa Muehlgrabner, Magdalena C. Schneider, Elke Kurz, Gerhard J. Schuetz, Johannes B. Huppa, Eva Sevcsik
Summary: DNA origami structures provide flexible scaffolds for organizing biomolecules with nanometer precision, but functionalizing them with proteins while maintaining stoichiometry and protein functionality remains challenging. This study systematically evaluated different strategies for site-specific decoration of DNA origami structures, with a focus on efficiency, stoichiometry, and protein functionality. The study found that using charge-neutral peptide nucleic acid emerged as the best strategy for achieving high yield and preserving protein functionality.
Article
Immunology
Xiang Zhao, Liang-Zhe Wu, Esther K. Y. Ng, Kerisa W. S. Leow, Qianru Wei, Nicholas R. J. Gascoigne, Joanna Brzostek
Summary: Co-agonist pMHC class I complexes recruit CD8-bound Lck to the immune synapse to modulate CD8(+) T cell signaling pathways, enhancing effector functions and proliferation. Furthermore, co-agonism can boost T cell proliferation through an extrinsic mechanism, priming neighboring CD8(+) T cells for enhanced Akt pathway activation and proliferation.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Lukas Susac, Mai T. Vuong, Christoph Thomas, Soren von Bulow, Caitlin O'Brien-Ball, Ana Mafalda Santos, Ricardo A. Fernandes, Gerhard Hummer, Robert Tampe, Simon J. Davis
Summary: This study reveals the structure of a tumor-reactive TCR complex bound to a melanoma-specific human class I pMHC, providing insights into the initiation of TCR signaling when the receptor binds to pMHC molecules.
Article
Biochemistry & Molecular Biology
Emma Silvester, Benjamin Vollmer, Vojtech Prazak, Daven Vasishtan, Emily A. Machala, Catheryne Whittle, Susan Black, Jonathan Bath, Andrew J. Turberfield, Kay Gruenewald, Lindsay A. Baker
Summary: Electron cryotomography (cryoET) has revolutionized our understanding of biological function by revealing molecular details of membranes, viruses, and cells. A new tagging strategy using DNA origami allows for precise identification of individual protein complexes in tomograms without relying on metal clusters, making it suitable for a wide range of biological surfaces in cryoET studies.
Article
Multidisciplinary Sciences
Rui Dong, Tural Aksel, Waipan Chan, Ronald N. Germain, Ronald D. Vale, Shawn M. Douglas
Summary: The spatial arrangement of receptors determines the ligand density threshold for triggering and encodes the temporal kinetics of signaling activities in triggering cellular activation. Cells measure spatial arrangements of ligands, translate that information into distinct signaling dynamics, providing insights into engineering immunotherapies.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Multidisciplinary Sciences
Muren Hu, Chang Feng, Qianqin Yuan, Chenbin Liu, Bujun Ge, Fenyong Sun, Xiaoli Zhu
Summary: mRNA delivery has shown great potential in the treatment of various diseases. Here, the authors develop a lantern-shaped flexible origami for the nanolization of single mRNA molecules and demonstrate efficient delivery of Smad4 mRNA, achieving the suppression of colorectal cancer tumor growth.
NATURE COMMUNICATIONS
(2023)
Article
Chemistry, Multidisciplinary
Xinpei Dai, Xiaoliang Chen, Xinxin Jing, Yinan Zhang, Muchen Pan, Mingqiang Li, Qian Li, Pi Liu, Chunhai Fan, Xiaoguo Liu
Summary: Integrating dissimilar materials at the nanoscale is crucial for modern electronics and optoelectronics. Researchers have developed a DNA origami-encoded strategy for integrating silica-metal heterostructures and revealed the underlying mechanisms. By programming the densities and lengths of protruding dsDNA strands on DNA origami, high site-addressability of material deposition was achieved.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Article
Chemistry, Analytical
Xiaotong Shen, Qingwen Ouyang, Hongwei Tan, Jin Ouyang, Na Na
Summary: Researchers designed stable single-stranded DNA (ssDNA) nanorobots by examining the dynamic folding of ssDNA in self-assemblies via molecular dynamics simulations. Two ssDNA strands were successfully assembled into nanorobots using two functional siRNAs, enabling multiple applications. The nanorobots were demonstrated to be stable, flexible, highly utilized, and low in folding errors. This study provides a computational pathway for constructing flexible and multifunctional ssDNA frameworks, expanding the biological application of nucleic acid nanostructures.
ANALYTICAL CHEMISTRY
(2023)
Review
Engineering, Biomedical
Lingyu Feng, Jiang Li, Jielin Sun, Lihua Wang, Chunhai Fan, Jianlei Shen
Summary: Materials capable of regulating the composition and structure of cell membranes to create engineered cells with specific functions are highly sought after. DNA, with its outstanding programmability and biocompatibility, stands out among other biomolecules for cell membrane engineering. The near-atomic precision of DNA nanostructures allows for the exploration of structure-property relationships on cell membranes. This review summarizes the latest developments in functional DNA nanostructures and their application in modifying cell membrane morphology, controlling ion transport, and synthesizing highly precise liposomes. Challenges and prospects of using DNA nanostructures for cell membrane engineering are also discussed.
ADVANCED HEALTHCARE MATERIALS
(2021)
Article
Chemistry, Multidisciplinary
Piyumi Wijesekara, Ying Liu, Weitao Wang, Elizabeth K. Johnston, Mara L. G. Sullivan, Rebecca E. Taylor, Xi Ren
Summary: This study demonstrated that DNA nanotiles can effectively predict cell-to-cell accessibility by anchoring on the glycocalyx, providing a functional measure of glycocalyx barrier integrity. Compared to PLB anchoring, the glycocalyx-anchoring mechanism enhanced cell-surface stability and cellular uptake of nanotiles.
Article
Chemistry, Multidisciplinary
Lele Sun, Fengyun Shen, Zijian Xiong, Yu Chao, Chunhai Fan, Zhuang Liu
Summary: Precisely organized antibody arrangements using DNA origami can enhance T cell activation and expand CD8+ T cells for tumor immunotherapy.
Article
Multidisciplinary Sciences
Yueyang Sun, Jiajia Sun, Mingshu Xiao, Wei Lai, Li Li, Chunhai Fan, Hao Pei
Summary: This study used DNA origami nanostructures as scaffolds to construct high-effective nanosized artificial antigen-presenting cells (aAPCs) for in vivo adoptive cell therapy. The quantitative analysis of ligand-receptor interactions in T cell activation was enabled by the DNA origami scaffold, leading to important insights into the rational design of molecular vaccines for cancer immunotherapy. The optimized DNA origami-based aAPCs showed effective tumor growth inhibiting capability in both in vitro and in vivo assays.
Article
Medicine, General & Internal
Anna-Margarita Schoetta, Theresa Stelzer, Gerold Stanek, Hannes Stockinger, Michiel Wijnveld
Summary: This study collected ticks in popular recreational areas in Vienna and found that the most prevalent pathogen was Borrelia burgdorferi sensu lato, which causes Lyme borreliosis in humans. Other pathogens such as Rickettsia, Babesia, Candidatus Neoehrlichia mikurensis (CNM), Anaplasma phagocytophilum, and Borrelia miyamotoi were also detected. This study identified hotspots for B. miyamotoi, which was detected in Vienna for the first time.
WIENER KLINISCHE WOCHENSCHRIFT
(2023)
Article
Biology
Astrid C. Erber, Angelika Wagner, Marianna Karachaliou, Maren Jeleff, Polyxeni Kalafatis, Manolis Kogevinas, Beata Peplonska, Isabel Santonja, Eva Schernhammer, Hannes Stockinger, Kurt Straif, Ursula Wiedermann, Thomas Waldhoer, Kyriaki Papantoniou
Summary: Data from a population-based study suggests that the time of day of COVID-19 vaccine administration has an impact on the level of antibodies produced. Morning vaccination was associated with the highest antibody levels, while midday vaccination was associated with the lowest levels. Further evaluation is needed to determine if this difference in antibody levels affects the level of protection against COVID-19.
JOURNAL OF BIOLOGICAL RHYTHMS
(2023)
Article
Chemistry, Multidisciplinary
Alexandra S. S. Eklund, Ralf Jungmann
Summary: Super-resolution microscopy has revolutionized sample characterization in the life sciences. DNA-PAINT is an easy-to-implement method that uses programmable binding of dye-labeled DNA to their respective docking strands. Peptide-PAINT, a new method, improves labeling by using short coiled-coil peptide sequences, but lacks multiplexing ability.
Article
Biology
Florian Schueder, Pierre Mangeol, Eunice HoYee Chan, Renate Rees, Juergen Schuenemann, Ralf Jungmann, Dirk Goerlich, Frank Schnorrer
Summary: Sarcomeres, the force-producing units of striated muscles, depend on the titin protein for their nanoarchitecture. This study used nanobodies and super-resolution microscopy to determine the location of two Drosophila titin homologs in flight muscles. The findings reveal the presence of these titin homologs and their role in muscle structure, providing insights into the organization of sarcomeres in non-vertebrates.
Article
Biology
Sebastian Strauss, Julia Acker, Guido Papa, Daniel Desiro, Florian Schueder, Alexander Borodavka, Ralf Jungmann
Summary: Rotaviruses form cytoplasmic protein-RNA granules called viroplasms during infection, which are important for segmented genome assembly and replication. Our study found that the distribution of viral RNA in viroplasms is different from the cytoplasmic RNA distribution, with the largest RNA being the most enriched. This suggests a selective RNA enrichment mechanism. The presence of 3' untranslated terminal regions and the localization of the viral polymerase VP1 in viroplasms are required for the accumulation of transcripts.
Article
Biophysics
Clara Bodner, Dominik Kiesenhofer, Gerhard J. Schuetz, Mario Brameshuber
Summary: The interplay and communication between cells rely on protein-protein interactions and the oligomerization of proteins. The TOCCSL approach combines photobleaching and single-molecule microscopy to detect the interactions of fluorescently labeled membrane proteins even at high surface densities. Extensive Monte Carlo simulations were used to provide a theoretical framework for quantitative interpretation of TOCCSL measurements.
BIOPHYSICAL JOURNAL
(2023)
Editorial Material
Biochemistry & Molecular Biology
Johannes B. Huppa, Gerhard J. Schuetz
Summary: T-cell antigen recognition is affected by tensile forces, which reduce the lifetime of stable stimulatory TCR-pMHC interactions more than less stable non-stimulatory TCR-pMHC interactions. The authors propose that forces hinder rather than enhance T-cell antigen discrimination, which is facilitated by force-shielding within the immunological synapse through cell adhesion via CD2/CD58 and LFA-1/ICAM-1.
Article
Multidisciplinary Sciences
Susanne C. M. Reinhardt, Luciano A. Masullo, Isabelle Baudrexel, Philipp R. Steen, Rafal Kowalewski, Alexandra S. Eklund, Sebastian Strauss, Eduard M. Unterauer, Thomas Schlichthaerle, Maximilian T. Strauss, Christian Klein, Ralf Jungmann
Summary: Fluorescence microscopy is a major characterization method in the life sciences, but current super-resolution techniques do not achieve Angstrom resolution. This study introduces a DNA-barcoding method that greatly improves the resolution of fluorescence microscopy, allowing for single-protein resolution in intact cells. The method also demonstrates Angstrom resolution for DNA origami.
Article
Multidisciplinary Sciences
Alexey Ferapontov, Marjan Omer, Isabelle Baudrexel, Jesper Sejrup Nielsen, Daniel Miotto Dupont, Kristian Juul-Madsen, Philipp Steen, Alexandra S. Eklund, Steffen Thiel, Thomas Vorup-Jensen, Ralf Jungmann, Jorgen Kjems, Soren Egedal Degn
Summary: The binding between B cell receptors (BCRs) and antigens triggers a response in B cells and eventually leads to antibody production. However, it is still unclear how BCRs are distributed on naive B cells and how antigen binding initiates the first step of BCR signaling. Using DNA-PAINT super-resolution microscopy, it has been discovered that most BCRs exist as monomers, dimers, or loosely associated clusters on resting B cells, with a nearest-neighbor inter-Fab distance of 20-30nm. By engineering monoclonal model antigens with precise control over affinity and valency, researchers found that the antigen can activate the BCR in an agonistic manner as affinity and avidity increase.
NATURE COMMUNICATIONS
(2023)
Article
Immunology
Peter A. Tauber, Bernhard Kratzer, Philipp Schatzlmaier, Ursula Smole, Cordula Koehler, Lisa Rausch, Jan Kranich, Doris Trapin, Alina Neunkirchner, Maja Zabel, Sabrina Jutz, Peter Steinberger, Gabriele Gadermaier, Thomas Brocker, Hannes Stockinger, Sophia Derdak, Winfried F. Pickl
Summary: This study used small molecule inhibitors to identify novel IL-2/Treg enhancing compounds. BX-795 was found to increase IL-2 production and inhibit Th2 cytokine secretion, inducing a Treg cell type similar to iTreg but lacking Foxp3 expression, and effectively treating allergic diseases by inhibiting Th2 inflammation.
FRONTIERS IN IMMUNOLOGY
(2023)
Review
Pharmacology & Pharmacy
Anna Ohradanova-Repic, Romana Prazenicova, Laura Gebetsberger, Tetiana Moskalets, Rostislav Skrabana, Ondrej Cehlar, Gabor Tajti, Hannes Stockinger, Vladimir Leksa
Summary: Lactoferrin is an iron-binding glycoprotein that is found in human exocrine fluids, especially breast milk. It has diverse roles in host defense, including modulating immune cell functions, sequestering iron, and binding to various surfaces. Lactoferrin can be cleaved to generate lactoferricin, which also has bioactive properties. This review discusses the structure, functions, and potential therapeutic uses of lactoferrin, lactoferricin, and other lactoferrin-derived peptides in treating infections and inflammatory conditions, with a focus on their potential use in treating COVID-19.
Article
Biochemistry & Molecular Biology
Rene Platzer, Joschka Hellmeier, Janett Gohring, Iago Doel Perez, Philipp Schatzlmaier, Clara Bodner, Margarete Focke-Tejkl, Gerhard J. Schuetz, Eva Sevcsik, Hannes Stockinger, Mario Brameshuber, Johannes B. Huppa
Summary: This study demonstrates that single freely diffusing agonist pMHC II can autonomously elicit a full T-cell response in a peptide-specific manner, while endogenous pMHC II has minimal impact on TCR engagement.
Article
Multidisciplinary Sciences
Christian Niederauer, Chikim Nguyen, Miles Wang-Henderson, Johannes Stein, Sebastian Strauss, Alexander Cumberworth, Florian Stehr, Ralf Jungmann, Petra Schwille, Kristina A. Ganzinger
Summary: DNA-PAINT-SPT technique overcomes the limitations of fluorophore photobleaching and significantly improves observation times in in vitro SPT experiments. It is now extended to enable simultaneous dual-colour detection, allowing the quantification of protein dimerization and live cell membrane protein tracking. The technique demonstrates improved performance compared to single-dye SPT.
NATURE COMMUNICATIONS
(2023)
Article
Medicine, General & Internal
Erika Garner-Spitzer, Angelika Wagner, Venugopal Gudipati, Anna-Margarita Schoetta, Maria Orola-Taus, Michael Kundi, Renate Kunert, Patrick Mayrhofer, Johannes B. Huppa, Hannes Stockinger, Rita Carsetti, Pia Gattinger, Rudolf Valenta, Bernhard Kratzer, Al Nasar Ahmed Sehgal, Winfried F. Pickl, Walter Reinisch, Gottfried Novacek, Ursula Wiedermann
Summary: Patients with inflammatory bowel disease (IBD) receiving anti-TNF-alpha treatment showed lower and faster waning antibody levels after SARS-CoV-2 vaccination, likely due to impaired formation and maintenance of S-specific B memory cells. In contrast, IBD patients receiving alpha 4 beta 7-integrin antagonists and controls had higher and more persistent antibody levels, which correlated with the increased levels of S-specific B memory cells.