Review
Immunology
Ryley D. McClelland, Tyce N. Culp, David J. Marchant
Summary: Viruses use host factors to enter cells and cause disease, and imaging techniques are crucial for studying virus entry and replication processes, providing insights into viral infection mechanisms. Quantifying viral images and using cryo-electron microscopy to gather structural information of viruses can help identify novel targets for antiviral therapeutics and vaccines.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2021)
Article
Optics
Jakob G. P. Lingg, Thomas S. Bischof, Bernardo A. Arus, Emily D. Cosco, Ellen M. Sletten, Christopher J. Rowlands, Oliver T. Bruns, Andriy Chmyrov
Summary: The development of fluorophores with photoemission beyond 1000 nm provides the opportunity to develop novel fluorescence microscopes sensitive to those wavelengths. Imaging at wavelengths beyond the visible spectrum enables imaging depths of hundreds of microns in intact tissue, making this attractive for volumetric imaging applications.
LASER & PHOTONICS REVIEWS
(2023)
Article
Multidisciplinary Sciences
Lisa Schindler, Katrin Wohlfahrt, Lara Gluhacevic von Kruechten, Olaf Prante, Max Keller, Simone Maschauer
Summary: This study demonstrates that modifying Arg(8) or Arg(9) by N-omega-carbamoylation and subsequent fluoroglycosylation provides a suitable approach for the development of NT(8-13) analogs as PET imaging agents for NTS1-expressing tumors.
SCIENTIFIC REPORTS
(2022)
Article
Medicine, Research & Experimental
Seth Winfree, Andrew T. McNutt, Suraj Khochare, Tyler J. Borgard, Daria Barwinska, Angela R. Sabo, Michael J. Ferkowicz, James C. Williams Jr, James E. Lingeman, Connor J. Gulbronson, Katherine J. Kelly, Timothy A. Sutton, Pierre C. Dagher, Michael T. Eadon, Kenneth W. Dunn, Tarek M. El-Achkar
Summary: The human kidney is a complex organ with various cell types. This study introduces new imaging modalities for studying the cellular makeup and spatial organization of the kidney. The VTEA software tool is developed for analyzing these complex imaging data sets and decoding the cellular and spatial complexity of the human kidney.
LABORATORY INVESTIGATION
(2023)
Article
Chemistry, Multidisciplinary
Guankui Wang, Markella Zannikou, Laren Lofchy, Yue Li, Hanmant Gaikwad, Irina Balyasnikova, Dmitri Simberg
Summary: The type of fluorescent label on liposomes significantly impacts their extravasation and accumulation in tumors. In animal experiments, indocarbocyanine lipids (ICLs) were found to spread and accumulate in tumor tissue more easily compared to fluorescent phospholipids (FPLs).
Article
Chemistry, Multidisciplinary
Tom Baladi, Jesper R. Nilsson, Audrey Gallud, Emanuele Celauro, Cecile Gasse, Fabienne Levi-Acobas, Ivo Sarac, Marcel R. Hollenstein, Anders Dahlen, Elin K. Esbjorner, L. Marcus Wilhelmsson
Summary: The study introduces a stealth labeling strategy to efficiently generate RNA transcripts and translate them into correct proteins, providing an important tool for biological research and RNA delivery studies.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2021)
Article
Chemistry, Multidisciplinary
Jun-Fang Wang, Chun-Miao Zhao, Jian-Xing Yang, Xu He, Xiao-Liu Li, Jin-Mei Li, Ke-Rang Wang
Summary: A mannose-modified perylene monoimide derivative PMI-Man has been developed, which exhibits highly selective binding to double-stranded DNA molecules, potent live/dead cell imaging, and histological imaging via both confocal and light microscopies. This approach may be utilized to create a universal colorful staining method for human tissues suitable for both confocal and light microscopies.
CHEMICAL COMMUNICATIONS
(2021)
Review
Virology
Soumajit Mukherjee, Emmanuel Boutant, Eleonore Real, Yves Mely, Halina Anton
Summary: Progress in bioimaging and fluorescent labeling strategies have enabled direct visualization of the early phase of the HIV-1 life cycle in infected cells. Imaging techniques provide detailed data on individual viruses and have shed light on viral entry into host cells, cytoplasmic transport, nuclear import, and integration site selection. Multi-color imaging studies have also contributed to understanding the role of host cell factors in the HIV-1 viral cycle progression.
Article
Biochemistry & Molecular Biology
Neus Gacias-Amengual, Lena Wohlschlager, Florian Csarman, Roland Ludwig
Summary: In this study, lignocellulosic enzymes from the white rot fungus Phanerochaete chrysosporium were localized on model substrates and poplar wood using confocal laser scanning microscopy. Two detection approaches were investigated, revealing the innermost secondary cell wall layer as the preferential attack point for cellulose-degrading enzymes. The methods presented are suitable for visualizing enzymes during catalytic biomass degradation and can be further utilized for interaction studies in biorefineries.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Immunology
Anika Gruneboom, Oliver Aust, Zuelal Cibir, Flora Weber, Dirk M. Hermann, Matthias Gunzer
Summary: Innate immune cells play a crucial role in defense against infections and sterile inflammation, with recent advances in microscopy providing insights into their biology. Neutrophils and macrophages have protective roles during tumor growth and ischemia-reperfusion damage, but can also exacerbate diseases. Future directions include enhancing knowledge about innate immune cells and their potential applications in disease diagnostics.
IMMUNOLOGICAL REVIEWS
(2022)
Article
Chemistry, Applied
Diego Navarro-Barreda, Begona Bedrina, Cesar A. A. Angulo-Pachon, Juan F. F. Miravet, Dolores Perez-Sala, Francisco Galindo
Summary: Four new BODIPY derivatives were synthesized and characterized, with a focus on their effects on cellular uptake, intracellular location, and fluorescence imaging abilities. The results showed that one of the new molecules displayed superior lysosomal location compared to the others.
Article
Cell Biology
Simone Pelicci, Laura Furia, Pier Giuseppe Pelicci, Mario Faretta
Summary: The modern fluorescence microscope combines different technologies with varying performance levels. However, the best results are achieved by maximizing one parameter while compromising others, which limits the adoption of new optical microscopy tools in research labs.
Article
Chemistry, Physical
Cecilia Zaza, German Chiarelli, Ludovit P. Zweifel, Mauricio Pilo-Pais, Evangelos Sisamakis, Fabio Barachati, Fernando D. Stefani, Guillermo P. Acuna
Summary: Fluorescence Resonance Energy Transfer (FRET)-based approaches are unique tools for sensing the immediate surroundings and interactions of (bio)molecules. FRET imaging and Fluorescence Lifetime Imaging Microscopy (FLIM) enable the visualization of the spatial distribution of molecular interactions and functional states. However, conventional FLIM and FRET imaging provide average information over an ensemble of molecules within a diffraction-limited volume, which limits the spatial information, accuracy, and dynamic range of the observed signals. Here, an approach to obtain super-resolved FRET imaging based on single-molecule localization microscopy using an early prototype of a commercial time-resolved confocal microscope is demonstrated. DNA Points Accumulation for Imaging in Nanoscale Topography with fluorogenic probes provides a suitable combination of background reduction and binding kinetics compatible with the scanning speed of usual confocal microscopes. A single laser is used to excite the donor, a broad detection band is employed to retrieve both donor and acceptor emission, and FRET events are detected from lifetime information.
Article
Optics
Gwinky G. K. Yip, Michelle C. K. Lo, Wenwei Yan, Kelvin C. M. Lee, Queenie T. K. Lai, Kenneth K. Y. Wong, Kevin K. Tsia
Summary: The new high-speed quantitative phase imaging (QPI) technique presented in this study combines time-interleaved phase-gradient FACED image detection, enabling fast imaging and cell analysis. Integration with microfluidic technology allows for high-speed, high-resolution imaging of cell phenotypes.
Article
Biochemical Research Methods
Zhi Lu, Yu Liu, Manchang Jin, Xin Luo, Huanjing Yue, Zian Wang, Siqing Zuo, Yunmin Zeng, Jiaqi Fan, Yanwei Pang, Jiamin Wu, Jingyu Yang, Qionghai Dai
Summary: Virtual-scanning light-field microscopy (VsLFM) uses a physics-based deep learning model to improve the quality and speed of LFM, reducing motion artifacts and enabling challenging demonstrations such as fast 3D voltage imaging in Drosophila. By constructing a 40 GB high-resolution scanning LFM dataset across different species, VsLFM exploits physical priors and bypasses hardware scanning to achieve ultrafast 3D imaging in various processes such as the beating heart in embryonic zebrafish and neutrophil migration in the mouse liver.
Article
Cell Biology
Xinyu Xu, Jonas Kaindl, Mary J. Clark, Harald Hubner, Kunio Hirata, Roger K. Sunahara, Peter Gmeiner, Brian K. Kobilka, Xiangyu Liu
Summary: Beta adrenergic receptors mediate physiological responses to catecholamines epinephrine and norepinephrine, and norepinephrine shows higher affinity for beta(1)AR. Crystal structure analysis revealed identical catecholamine-binding pockets but differences in extracellular vestibules between beta(1)AR and beta(2)AR, influencing norepinephrine binding path and affinity.
Article
Biochemistry & Molecular Biology
Tamara Ullmann, Marie Gienger, Julian Budzinski, Jan Hellmann, Harald Huebner, Peter Gmeiner, Dorothee Weikert
Summary: The study synthesized homobivalent ligands that promote D2R homodimerization and reduce interactions between D2R and NTSR1. These newly developed bivalent ligands are useful tools for understanding the pharmacological consequences of D2R homo- and heterodimerization.
ACS CHEMICAL BIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
James I. Mitchell-White, Thomas Stockner, Nicholas Holliday, Stephen J. Briddon, Ian D. Kerr
Summary: Members of the mammalian G subfamily of ATP-binding cassette transporters exhibit significant differences in substrate specificity, with ABCG2 playing a crucial role in multidrug resistance due to its wide substrate specificity. Analysis of conservation differences between members in a multiple sequence alignment of ABCG sequences from mammals reveals possible explanations for functional differences. Mapping sets of residues onto the 3D structure of ABCG2 illustrates a network of residues that may confer additional conformational flexibility, allowing for transport of a wider array of substrates.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Vanessa Boritzki, Harald Hubner, Anni Allikalt, Peter Gmeiner, Birgitta M. Wohrl
Summary: The study focused on expressing human dopamine receptors D-2S and D-3 in Escherichia coli using different fusion proteins and mutations to optimize expression and evaluate ligand binding. Results showed that the presence of a C-terminal fusion protein, but not the type, is important for receptor expression. Improved receptor variants with high affinity ligand binding can be selected using FACS analysis and error-prone PCR.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Chemistry, Medicinal
Katharina Tropmann, Merlin Bresinsky, Lisa Forster, Denise Moennich, Armin Buschauer, Hans-Joachim Wittmann, Harald Huebner, Peter Gmeiner, Steffen Pockes, Andrea Strasser
Summary: Novel carbamoylguanidine-type ligands were designed, synthesized, and tested for their selectivity as H2R agonists, revealing promising candidates and providing a basis for further exploration of H2R functions in the brain.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Multidisciplinary Sciences
Marc Bathe-Peters, Philipp Gmach, Horst-Holger Boltz, Jurgen Einsiedel, Michael Gotthardt, Harald Huebner, Peter Gmeiner, Martin J. Lohse, Paolo Annibale
Summary: Two beta-adrenergic receptor subtypes, beta(1) and beta(2), show different localizations and diffusions in cardiomyocytes, with the segregation depending on the development of the T-tubular network, leading to distinct signaling and functional effects.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Biology
Julian Budzinski, Simone Maschauer, Hiroyuki Kobayashi, Pierre Couvineau, Hannah Vogt, Peter Gmeiner, Anna Roggenhofer, Olaf Prante, Michel Bouvier, Dorothee Weikert
Summary: The study demonstrates specific interactions between dopamine D3 receptor and neurotensin receptor 1 using bivalent ligands, showing potential role of dimerization in vivo. The bivalent ligands enhance and stabilize the receptor-receptor interaction, resulting in specific receptor trafficking and signaling.
COMMUNICATIONS BIOLOGY
(2021)
Article
Multidisciplinary Sciences
Geng Chen, Jun Xu, Asuka Inoue, Maximilian F. Schmidt, Chen Bai, Qiuyuan Lu, Peter Gmeiner, Zheng Liu, Yang Du
Summary: This study reports two structures of the human GPR88-Gi complex, revealing an allosteric ligand involved in the interaction between the receptor and G-protein, and a potential endogenous ligand of GPR88.
NATURE COMMUNICATIONS
(2022)
Article
Biochemistry & Molecular Biology
James P. Farmer, Shailesh N. Mistry, Charles A. Laughton, Nicholas D. Holliday
Summary: This study developed fluorescent-labeled peptides as novel binding and activation biosensors for the GPCR-IAM site, allowing the assessment of the affinity of unlabeled ligands for the receptor and providing a new method for screening IAMs. Moreover, this method can be used to investigate the efficacy of orthosteric agonists and the dynamics of receptor activation.
Article
Chemistry, Medicinal
Johannes Koeckenberger, Oliver Fischer, Andreas Konopa, Sebastian Bergwinkl, Susanne Muehlich, Peter Gmeiner, Roger Jan Kutta, Harald Huebner, Max Keller, Markus R. Heinrich
Summary: Two novel tool compounds, OFH5503 and OFH611, have been developed by linking fluorescent dyes and muscarinergic M-3 receptor ligands. These conjugates can be useful tools for determining binding affinities and studying receptor expression.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Multidisciplinary Sciences
Jun Xu, Qinggong Wang, Harald Huebner, Yunfei Hu, Xiaogang Niu, Haoqing Wang, Shoji Maeda, Asuka Inoue, Yuyong Tao, Peter Gmeiner, Yang Du, Changwen Jin, Brian K. Kobilka
Summary: In this study, the authors used cryo-EM and NMR to investigate the mechanisms underlying the signaling versatility of M2R. They found that acetylcholine stabilizes a more heterogeneous M2R-G-protein complex than iperoxo, and LY2119620 modulates agonist efficacy in G-protein and beta-arrestin pathways differently. These findings highlight the importance of conformational dynamics in the complex signaling behavior of GPCRs.
NATURE COMMUNICATIONS
(2023)
Article
Chemistry, Medicinal
Lukas Waterloo, Harald Hubner, Fabrizio Fierro, Tara Pfeiffer, Regine Brox, Stefan Loeber, Dorothee Weikert, Masha Y. Niv, Peter Gmeiner
Summary: The TAS2R14 receptor, found in the tongue, human airway smooth muscle, and other tissues, is a potential target for asthma and chronic obstructive pulmonary disease treatment. By modifying the structure of flufenamic acid, we developed a set of promising TAS2R14 agonists, particularly ligand 28.1, which showed higher potency and selectivity compared to flufenamic acid and other taste receptors.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Medicinal
Fabian Grassl, Leonard Bock, Alvaro Huete-Huerta Gonzalez, Martin Schiller, Peter Gmeiner, Joerg Koenig, Martin F. Fromm, Harald Huebner, Markus R. Heinrich
Summary: Based on APH199, two novel groups of D-4 subtype selective ligands were designed and evaluated, showing bias toward G(i) signaling pathway over β-arrestin recruitment compared to quinpirole. These compounds exhibited different bias profiles in terms of efficacy, potency, and GRK2 dependency, ranging from 1 to over 300 bias factors and activation from 15% to over 98% compared to quinpirole. Docking studies provided insights into the role of ECL2 and EPB in bias emergence, utilizing the diversity of functionally selective D-4 agonists.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Medicinal
Bianca Maria Casella, James P. P. Farmer, Desislava N. N. Nesheva, Huw E. L. Williams, Steven J. J. Charlton, Nicholas D. D. Holliday, Charles A. A. Laughton, Shailesh N. N. Mistry
Summary: Inhibition of CXCR2 is a potential strategy for the treatment of pulmonary diseases and cancers. This study reports the design and synthesis of fluorescent NAMs that selectively bind to CXCR2, enabling the measurement and evaluation of their pharmacological properties. These NAMs can be used as alternative compounds for targeting these receptors.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Medicinal
Lukas Waterloo, Harald Huebner, Fabrizio Fierro, Tara Pfeiffer, Regine Brox, Stefan Loeber, Dorothee Weikert, Masha Y. Niv, Peter Gmeiner
Summary: TAS2R14 is a bitter taste receptor found in multiple locations, including the tongue and human airway smooth muscle. Activation of TAS2R14 can lead to bronchodilation, making it a potential target for treating asthma or chronic obstructive pulmonary disease. By modifying the structure of flufenamic acid, a study identified a group of effective and potent TAS2R14 agonists called 2-aminopyridines with a tetrazole unit. The most potent ligand, 28.1, showed a six-fold higher potency than flufenamic acid and demonstrated selectivity over other human taste receptors.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)