Review
Pharmacology & Pharmacy
Melissa S. Love, Case W. McNamara
Summary: Recent advancements in drug discovery efforts for cryptosporidiosis have been inspired by the challenges posed by the unique biology of Cryptosporidium. Phenotypic-based screens and repositioning of hits from other pathogens have created a pipeline of potential therapeutics for this disease. Improved methodologies in phenotypic assays are facilitating the development of new compounds for clinical testing.
EXPERT OPINION ON DRUG DISCOVERY
(2021)
Article
Chemistry, Physical
Matthew Bain, Jose L. Godinez Castellanos, Stephen E. Bradforth
Summary: High-repetition-rate lasers have the potential to revolutionize ultrafast spectroscopy by enabling routine analysis for machine learning models in the design of photochemical syntheses. In this study, we combine innovations in line scan cameras and micro-electro-mechanical grating modulators with high-pressure liquid chromatography pumps to develop a transient absorption spectrometer that can characterize photoreactions in minutes. Additionally, we demonstrate the utility of this technique in exploring the effects of conformational modification on excited-state processes.
JOURNAL OF PHYSICAL CHEMISTRY LETTERS
(2023)
Article
Chemistry, Medicinal
Yiwei Zhang, Jiabei Guo, Jiongjia Cheng, Zhenghua Zhang, Fenghua Kang, Xiaoxing Wu, Qian Chu
Summary: Therapeutic peptides have revolutionized treatment for many human diseases. In recent decades, stapled helical peptides have made rapid progress in drug discovery. Compared to unstabilized linear peptides, stapled helical peptides have shown superior binding affinity, selectivity, membrane permeability, and metabolic stability, offering exciting potential for targeting challenging protein-protein interfaces. This Perspective summarizes the recent use of high-throughput screening technologies for identifying potent stapled helical peptides with optimized binding properties, aiming to accelerate the development of stapled helical peptides as the next generation of therapeutic peptides for various human diseases.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Multidisciplinary Sciences
Zhenzhen Wang, Jiangjiexing Wu, Jia-Jia Zheng, Xiaomei Shen, Liang Yan, Hui Wei, Xingfa Gao, Yuliang Zhao
Summary: The study uses density functional theory calculations to investigate the principles behind the SOD-like catalytic activity of nanomaterials, proposing energy level and adsorption energy principles for quantitatively describing the activity. These principles were validated through experiments on metal-organic frameworks and can be easily implemented in computer programs for screening NMs with intrinsic SOD-like activity. A general predicting theory for superoxide-dismutase mimicking nanomaterials is currently lacking.
NATURE COMMUNICATIONS
(2021)
Article
Virology
Kang Ning, Anuradha Roy, Fang Cheng, Peng Xu, Steve Kleiboeker, Carlos R. Escalante, Jingxin Wang, Jianming Qiu
Summary: This study developed a high-throughput screening assay for identifying antivirals against B19V replication and discovered a purine derivative that exhibited significant antiviral activity against B19V infection.
JOURNAL OF VIROLOGY
(2022)
Article
Pharmacology & Pharmacy
Yayoi Honda, Jun Li, Aya Hino, Shinji Tsujimoto, Jong-Kook Lee
Summary: Evaluation of drug-induced arrhythmia is crucial for drug discovery, and new evaluation systems based on human iPS cell-derived cardiomyocytes have been established. With the increasing incidence of atrial arrhythmias and the lack of established experimental methods, a high-throughput drug evaluation system using atrial-like cardiomyocytes has been developed to detect potential risks for drug-induced atrial arrhythmias.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Medicine, Research & Experimental
Pallavi Bhatta, Kevin D. Whale, Amy K. Sawtell, Clare L. Thompson, Stephen E. Rapecki, David A. Cook, Breda M. Twomey, Milena Mennecozzi, Laura E. Starkie, Emily M. C. Barry, Shirley J. Peters, Ahmad M. Kamal, Helene M. Finney
Summary: This study presents a high-throughput, combinatorial, phenotypic screening approach for bispecific antibody target discovery, allowing screening of hundreds of target combinations. The research identified a potent bispecific antibody inhibiting human B cell activation and another one inhibiting human cell matrix accumulation.
Review
Developmental Biology
Zoe C. Johnston, Franz S. Gruber, Sean G. Brown, Neil R. Norcross, Jason Swedlow, Ian H. Gilbert, Christopher L. R. Barratt
Summary: Despite recent advances, there is still incomplete understanding of male infertility and male non-hormonal contraceptives. Direct observation of compounds' effects on sperm function can increase knowledge and advance the field.
Review
Chemistry, Multidisciplinary
Xabier Rodriguez-Martinez, Enrique Pascual-San-Jose, Mariano Campoy-Quiles
Summary: The discovery of novel high-performing materials in organic solar cells has rapidly increased efficiency, but traditional experimentation methods are unable to evaluate the vast catalog of materials efficiently. High-throughput experimental and computational methods are being utilized to accelerate the discovery of new materials, with machine-learning algorithms playing a key role in retrieving quantitative structure-activity relationships.
ENERGY & ENVIRONMENTAL SCIENCE
(2021)
Review
Biochemistry & Molecular Biology
Agni F. M. Gavriilidou, Kleitos Sokratous, Hsin-Yung Yen, Luigi De Colibus
Summary: Studying protein-ligand interactions can greatly assist in the design of new therapeutic molecules. Various techniques used in drug discovery, such as isothermal titration calorimetry and nuclear magnetic resonance spectroscopy, rely on protein crystallography and cryo-electron microscopy. Native mass spectrometry is a versatile method for studying proteins and their interactions, providing valuable insights into protein structure and thermodynamics.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2022)
Article
Chemistry, Medicinal
Alexander Neumann, Isaac Attah, Haneen Al-Hroub, Vigneshwaran Namasivayam, Christa E. Mueller
Summary: The human ATP- and UTP-activated P2Y2 receptor plays a role in various pathological conditions. However, the current P2Y2 receptor antagonists have limitations. In this study, researchers utilized virtual screening and molecular docking to discover novel antagonist scaffolds for the P2Y2 receptor. The identified compounds showed similar binding modes with a known potent orthosteric antagonist. This study provides a basis for the development of future drug candidates for the P2Y2 receptor.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2022)
Article
Chemistry, Physical
Byung Chul Yeo, Hyunji Nam, Hyobin Nam, Min-Cheol Kim, Hong Woo Lee, Sung-Chul Kim, Sung Ok Won, Donghun Kim, Kwan-Young Lee, Seung Yong Lee, Sang Soo Han
Summary: The study introduces a high-throughput screening protocol for discovering alternative catalysts to palladium, identifying a previously unreported bimetallic catalyst with enhanced performance and productivity.
NPJ COMPUTATIONAL MATERIALS
(2021)
Review
Chemistry, Multidisciplinary
Shulin Luo, Tianshu Li, Xinjiang Wang, Muhammad Faizan, Lijun Zhang
Summary: Optoelectronic semiconductors have attracted significant research attention for large-scale applications, and high-throughput computational screening has emerged as a useful tool to accelerate materials discovery, leading to the construction of diverse material databases.
WILEY INTERDISCIPLINARY REVIEWS-COMPUTATIONAL MOLECULAR SCIENCE
(2021)
Review
Pharmacology & Pharmacy
Fabio Stossi, Pankaj K. Singh, Kazem Safari, Michela Marini, Demetrio Labate, Michael A. Mancini
Summary: Measuring single cell responses to chemicals is crucial for human health, and high throughput, microscopy-based assays coupled with multi-dimensional single cell analysis methods are being used to address this problem. This article summarizes efforts in this field, focusing on environmental toxicology and drug screening, and discusses the advantages and limitations of high throughput assays.
BIOCHEMICAL PHARMACOLOGY
(2023)
Article
Chemistry, Multidisciplinary
Yifeng Tang, Jeremiah Y. Kim, Carman K. M. Ip, Azadeh Bahmani, Qing Chen, Matthew G. Rosenberger, Aaron P. Esser-Kahn, Andrew L. Ferguson
Summary: A machine learning-enabled active learning pipeline was developed to guide the screening and discovery of small molecule immunomodulators that can improve immune responses. By using high throughput screening and data-driven predictive models, novel small molecules with enhanced or suppressed innate immune signaling capacity were discovered, and chemical design rules were extracted.
Article
Cell & Tissue Engineering
Kee-Pyo Kim, Cui Li, Daria Bunina, Hyun-Woo Jeong, Julia Ghelman, Juyong Yoon, Borami Shin, Hongryeol Park, Dong Wook Han, Judith B. Zaugg, Johnny Kim, Tanja Kuhlmann, Ralf H. Adams, Kyung-Min Noh, Steven A. Goldman, Hans R. Schoeler
Summary: By transducing an optimized transcription factor combination into a permissive donor phenotype, pericyte-derived iOPCs (PC-iOPCs) can overcome the limitations of inefficient generation and limited expansion and differentiation competence. PC-iOPCs are stably expandable and functionally myelinogenic with high differentiation competence.
Article
Biochemistry & Molecular Biology
Daisylyn Senna Tan, Yanpu Chen, Ya Gao, Anastasia Bednarz, Yuanjie Wei, Vikas Malik, Derek Hoi-Hang Ho, Mingxi Weng, Sik Yin Ho, Yogesh Srivastava, Sergiy Velychko, Xiaoxiao Yang, Ligang Fan, Johnny Kim, Johannes Graumann, Gary D. Stormo, Thomas Braun, Jian Yan, Hans R. Schoeler, Ralf Jauch
Summary: Transcription factor-driven cell fate engineering requires efficiency, speed, and maturity for clinical translation. Directed evolution led to the discovery of an artificially evolved POU factor (ePOU) that surpasses Oct4 in reprogramming efficacy. ePOU can induce pluripotency with or without Sox2, has altered DNA binding preferences, and accelerates pluripotency network establishment.
MOLECULAR BIOLOGY AND EVOLUTION
(2021)
Article
Cell & Tissue Engineering
Konstantina Chanoumidou, Benjamin Hernandez-Rodriguez, Farina Windener, Christian Thomas, Martin Stehling, Sabah Mozafari, Stefanie Albrecht, Linda Ottoboni, Jack Antel, Kee-Pyo Kim, Sergiy Velychko, Qiao Ling Cui, Yu Kang T. Xu, Gianvito Martino, Jurgen Winkler, Hans R. Scholer, Anne Baron-Van Evercooren, Odile Boespflug-Tanguy, Juan M. Vaquerizas, Marc Ehrlich, Tanja Kuhlmann
Summary: Limited access to human oligodendrocytes hinders the understanding of oligodendrocyte pathology in myelin diseases. A method to convert human fibroblasts into oligodendrocyte-like cells has been developed, allowing for evaluation of remyelination-promoting compounds and disease modeling. This technology represents a reproducible approach that could contribute to personalized medicine in the field of myelin diseases.
Article
Multidisciplinary Sciences
Eva M. Mall, Aaron Lecanda, Hannes C. A. Drexler, Erez Raz, Hans R. Scholer, Stefan Schlatt
Summary: DND1 plays crucial roles in the survival and development of germ cells in zebrafish and mice, but its specific role in human pluripotency and germline development remains unclear. Using CRISPR/Cas knockout, it was found that DND1 does not affect pluripotency but reduces PGCLC differentiation, with altered gene expression patterns in mutated PGCLCs.
Article
Multidisciplinary Sciences
Dong Han, Guangming Wu, Rui Chen, Hannes C. A. Drexler, Caitlin M. MacCarthy, Kee-Pyo Kim, Kenjiro Adachi, Daniela Gerovska, Lampros Mavrommatis, Ivan Bedzhov, Marcos J. Arauzo-Bravo, Hans R. Schoeler
Summary: This study reveals the importance of Oct4 linker interface-mediated interactions in maintaining pluripotency. Mutations in the linker disrupt the balanced Oct4 interactome, leading to impaired epigenetic state and self-renewal ability of embryonic stem cells. Restoring the expression levels of related factors can rescue the pluripotency of linker mutant ESCs.
Article
Multidisciplinary Sciences
Farsam Eliat, Rebecca Sohn, Henrik Renner, Theresa Kagermeier, Stefan Volkery, Heike Brinkmann, Nils Kirschnick, Friedemann Kiefer, Martha Grabos, Katharina Becker, Ivan Bedzhov, Hans R. Schoeler, Jan M. Bruder
Summary: In recent years, 3D cell culture has become increasingly popular in various fields of biology. Tissue clearing techniques allow for optical analysis of intact 3D samples by making them transparent. However, the common clearing solutions used in this process can alter the emission spectra of fluorophores and fluorescent dyes. This poses a challenge in quantitative multiband excitation experiments as it increases the risk of unexpected channel crosstalk. Therefore, researchers should crosscheck the fluorescent signals after tissue clearing to select the appropriate filter sets and fluorophores for analysis.
SCIENTIFIC REPORTS
(2022)
Article
Biology
Le Xiong, Erik A. Tolen, Jinmi Choi, Sergiy Velychko, Livia Caizzi, Taras Velychko, Kenjiro Adachi, Caitlin M. MacCarthy, Michael Lidschreiber, Patrick Cramer, Hans R. Schoeler
Summary: The transcription factor Oct4 is essential for stem cell pluripotency, and this study investigates its functions by depleting and recovering it in embryonic stem cells. Oct4 depletion results in loss of binding to enhancers and decreased mRNA synthesis of target genes involved in maintaining pluripotency. Partial recovery of Oct4 expression increases chromatin accessibility but does not fully restore enhancer transcription. These findings suggest that Oct4 has concentration-dependent activities.
Article
Cell & Tissue Engineering
Yotam Menuchin-Lasowski, Andre Schreiber, Aaron Lecanda, Angeles Mecate-Zambrano, Linda Brunotte, Olympia E. Psathaki, Stephan Ludwig, Thomas Rauen, Hans R. Schoeler
Summary: Several studies have shown that SARS-CoV-2 can infect and replicate in retinal cells, inducing inflammatory responses and relying on ACE2 for infection. Therefore, it is important to monitor the potential effects of COVID-19 on the retina.
Article
Cell Biology
Rene Guenther, Arun Pal, Chloe Williams, Vitaly L. Zimyanin, Maria Liehr, Clare von Neubeck, Mechthild Krause, Mrudula G. Parab, Susanne Petri, Norman Kalmbach, Stefan L. Marklund, Jared Sterneckert, Peter Munch Andersen, Florian Wegner, Jonathan D. Gilthorpe, Andreas Hermann
Summary: Little is known about the early pathogenic events of mutant SOD1 in ALS. Using a human iPSC model, this study reveals that mitochondrial dysfunction is one of the crucial early steps in the pathogenic cascade of SOD1-ALS.
Article
Biochemistry & Molecular Biology
Caitlin M. MacCarthy, Jan Huertas, Claudia Ortmeier, Hermann vom Bruch, Daisylyn Senna Tana, Deike Reinke, Astrid Sander, Tim Bergbrede, Ralf Jauch, Hans R. Schoeler, Vlad Cojocaru
Summary: Through experiments and molecular simulations, this study reveals how the pioneer factor Oct4 interprets and enhances nucleosome structural flexibility. Oct4 uses its DNA binding domains to propagate and stabilize open nucleosome conformations, providing a structural basis for the versatility of transcription factors' interaction with nucleosomes.
NUCLEIC ACIDS RESEARCH
(2022)
Article
Cell Biology
Vitaly L. Zimyanin, Anna-Maria Pielka, Hannes Glass, Julia Japtok, Dajana Grossmann, Melanie Martin, Andreas Deussen, Barbara Szewczyk, Chris Deppmann, Eli Zunder, Peter M. Andersen, Tobias M. Boeckers, Jared Sterneckert, Stefanie Redemann, Alexander Storch, Andreas Hermann
Article
Cell Biology
Bita Massih, Alexander Veh, Maren Schenke, Simon Mungwa, Bettina Seeger, Bhuvaneish T. Selvaraj, Siddharthan Chandran, Peter Reinhardt, Jared Sterneckert, Andreas Hermann, Michael Sendtner, Patrick Lueningschroer
Summary: This article introduces a human neuromuscular co-culture system that enables the formation of neuromuscular junctions by differentiating induced pluripotent stem cells into motor neurons and 3D skeletal muscle tissue. The system is suitable for modeling the pathophysiology of motor neuron diseases and has been used to study the synaptic coupling and muscle contraction in Amyotrophic Lateral Sclerosis (ALS). This in vitro model recapitulates aspects of human physiology and is of great importance for studying human motor neurons in health and disease.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2023)
Article
Cell Biology
Cristina Marisol Castillo Bautista, Kristin Eismann, Marc Gentzel, Silvia Pelucchi, Jerome Mertens, Hannah E. Walters, Maximina H. Yun, Jared Sterneckert
Summary: Aging disrupts protein homeostasis and contributes to various diseases, including ALS. Repressing autophagy is a strategy to restore protein homeostasis and protect neurons. A study found that obatoclax, a small molecule BH3 mimetic, can disrupt the interaction between BECN1 and BCL2, reducing FUS levels and improving protein homeostasis to rescue neurons. Obatoclax has potential as a therapeutic for ALS and other age-related disorders linked to protein homeostasis defects.
Article
Cell Biology
Francesco Antoniani, Marco Cimino, Laura Mediani, Jonathan Vinet, Enza M. Verde, Valentina Secco, Alfred Yamoah, Priyanka Tripathi, Eleonora Aronica, Maria E. Cicardi, Davide Trotti, Jared Sterneckert, Anand Goswami, Serena Carra
Summary: Amyotrophic Lateral Sclerosis (ALS) and Frontotemporal Dementia (FTD) are neurodegenerative disorders linked by genetic causes, with TARDBP, FUS, and C9orf72 genes playing critical roles. The proteins produced by these genes accumulate in the cytoplasm, leading to pathological inclusions. This study explores the connection between the cytoplasmic and nuclear protein quality control (PQC) systems, highlighting the impairment of PML nuclear bodies (PML-NBs) and cytoplasmic stress granules (SGs) in ALS-FTD cases, which contribute to protein aggregation.
CELL DEATH DISCOVERY
(2023)
Article
Chemistry, Multidisciplinary
Jann Harberts, Katja Bours, Malte Siegmund, Carina Hedrich, Michael Glatza, Hans R. Scholer, Undine Haferkamp, Ole Pless, Robert Zierold, Robert H. Blick
Summary: Culturing human induced pluripotent stem cell-derived neural progenitor cells on nanowire arrays showed reduced proliferation on arrays with the smallest array pitch and long nanowires. Cell numbers on larger pitches depended on nanowire lengths, with heavy deformations of the cell membrane observed. Despite massive deformation, cell viability was maintained at about 85%.
