Article
Chemistry, Multidisciplinary
Maximilian Fottner, Johannes Heimgartner, Maximilian Gantz, Rahel Muehlhofer, Timon Nast-Kolb, Kathrin Lang
Summary: Asparaginyl endopeptidases (AEPs) are important tools for peptide and protein modification, with wide applications in therapeutic and diagnostic fields. Using genetic code expansion, we achieved site-specific modification of target proteins, providing a simple and flexible labeling approach for creating diverse conjugates.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2022)
Article
Chemistry, Multidisciplinary
Rambabu N. Reddi, Adi Rogel, Efrat Resnick, Ronen Gabizon, Pragati Kishore Prasad, Neta Gurwicz, Haim Barr, Ziv Shulman, Nir London
Summary: Chemical modifications of proteins can impact various aspects of protein function, but there are limited methods for site-specific labeling in cells. The CoLDR strategy presented in this study allows for the installation of functional tags on target proteins while preserving their activity, enabling a wide range of applications. This approach, which includes labeling various proteins and assessing protein activity in a native environment, contributes to the tools available in chemical biology.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2021)
Article
Neurosciences
Laurentius (Renzo) Huber, Benedikt A. Poser, Amanda L. Kaas, Elizabeth J. Fear, Sebastian Dresbach, Jason Berwick, Rainer Goebel, Robert Turner, Aneurin J. Kennerley
Summary: The study validates the signal source of layer-dependent VASO fMRI using a rat model, showing high reliability in estimating layer-specific CBV changes. This validation study increases the neuronal interpretability of human layer-dependent VASO fMRI in neuroscience application studies.
Review
Genetics & Heredity
Rasa Elmentaite, Cecilia Dominguez Conde, Lu Yang, Sarah A. Teichmann
Summary: The development of single-cell and spatial transcriptomics methods has enabled the conception of the Human Cell Atlas initiative, aiming to generate an integrated map of all cells in the human body. By studying human tissues using single-cell gene expression data, we are gaining insights into the commonalities and tissue-specific features of major and supportive cell types within human organs.
NATURE REVIEWS GENETICS
(2022)
Article
Biochemistry & Molecular Biology
Ming-an Sun, Gernot Wolf, Yejun Wang, Anna D. Senft, Sherry Ralls, Jinpu Jin, Caitlin E. Dunn-Fletcher, Louis J. Muglia, Todd S. Macfarlan
Summary: The study identified numerous lineage-specific gene expression in different mammalian placentae, shedding light on the evolutionary process of placenta. The overlap between specific families of endogenous retroviruses and lineage-specific placental enhancers likely facilitates the lineage-specific evolution of the mammalian placenta.
MOLECULAR BIOLOGY AND EVOLUTION
(2021)
Article
Multidisciplinary Sciences
Daniel D. Sprockett, Jeffrey D. Price, Anthony F. Juritsch, Robert J. Schmaltz, Madalena V. F. Real, Samantha L. Goldman, Michael Sheehan, Amanda E. Ramer-Tait, Andrew H. Moeller
Summary: Mammalian species have distinct gut microbial communities, but the mechanisms maintaining symbionts specificity to hosts are unclear. This study shows that natural selection in house mice drives deterministic assembly of their gut microbiota. Native bacteria outcompeted non-native bacteria in both wild-type and immunodeficient mice, suggesting a home-site advantage for native microbiota independent of host adaptive immunity.
Article
Plant Sciences
Alexander Watson-Lazowski, Emma Raven, Doreen Feike, Lionel Hill, J. Elaine Barclay, Alison M. Smith, David Seung
Summary: Loss of PTST2 protein has variable effects on carbohydrate metabolism, physiology, and granule morphology in different grass species. Loss of PTST2 results in fewer and larger starch granules in wheat, fewer granules and lower starch content in barley, and almost complete loss of starch in Brachypodium. The loss of starch in Brachypodium leaves is accompanied by high levels of ADP-glucose and detrimental effects on growth and physiology. Loss of PTST2 also leads to abnormal granule formation in Brachypodium seeds.
JOURNAL OF EXPERIMENTAL BOTANY
(2022)
Article
Biochemical Research Methods
Yichen Xiang, Dhruva Katrekar, Prashant Mali
Summary: In this chapter, two strategies for achieving site-specific A-to-I RNA editing are presented: recruitment of endogenous ADARs and recruitment of exogenous ADARs. The use of circular adRNAs and a split-ADAR2 system enable robust and specific editing in various RNA editing applications.
Article
Chemistry, Multidisciplinary
Daniel Richter, Edgars Lakis, Jorn Piel
Summary: The tetrazine ligation is a versatile and fast reaction commonly used for bioorthogonal modifications. However, the incorporation of dienophiles in biomolecules has been limited by the need for externally added reagents. This study introduces a novel strategy, called TyrEx cycloaddition, which enables autonomous dienophile generation in bacteria. This technique has been successfully applied for the labeling of proteins and holds potential for various applications.
Article
Oncology
Margaret C. Steiner, Jez L. Marston, Luis P. Iniguez, Matthew L. Bendall, Katherine B. Chiappinelli, Douglas F. Nixon, Keith A. Crandall
Summary: Research implicates that HERVs are involved in various cancers, with differential expression identified in prostate, breast, and colon cancers. The study highlights potential biomarkers and therapeutic targets in these cancers, providing insights into the role of HERVs in cancer pathogenesis.
Article
Cell Biology
Zhen Lu, Noreen McBrearty, Jinyun Chen, Vivek S. Tomar, Hongru Zhang, Gianluca De Rosa, Aiwen Tan, Aalim M. Weljie, Daniel P. Beiting, Zhen Miao, Subin S. George, Allison Berger, Gurpanna Saggu, J. Alan Diehl, Constantinos Koumenis, Serge Y. Fuchs
Summary: The factors derived from tumors affect the activity and viability of tumor-specific cytotoxic T lymphocytes (CTLs), but the underlying mechanism is not well understood. These tumor-derived factors alter the lipid composition of cells and regulate the effector trogocytosis between cells. This process is controlled by the ATF3-CH25H axis, which affects tumor immunity, tumor growth, and the efficacy of CAR cell therapy.
Article
Chemistry, Analytical
Yang Li, Mingwei Sun, Yechen Hu, Yichu Shan, Zhen Liang, Lihua Zhang, Yukui Zhang
Summary: The study introduces an antibody-free strategy to simultaneously enrich and profile endogenous SUMO1/2/3-modified peptides, allowing for a comprehensive mapping of various endogenous SUMOylation sites.
ANALYTICA CHIMICA ACTA
(2021)
Article
Chemistry, Analytical
Bastiaan L. Duivelshof, Alain Beck, Davy Guillarme, Valentina D'Atri
Summary: Bispecific antibodies are an important class of biopharmaceutical drugs, with chain-association being a critical challenge in their development and production. This study developed an analytical workflow using various chromatographic modes combined with high resolution mass spectrometry, and successfully applied it to Hemlibra (emicizumab).
Article
Biochemistry & Molecular Biology
Westley Pawloski, Teppei Komiyama, Christos Kougentakis, Ananya Majumdar, David Fushman
Summary: The physiological consequences of varying in vivo CO2 levels point to a general mechanism for CO2 to influence cellular homeostasis beyond regulating pH. Little is known about the physiological responses induced by transitory and ubiquitous carbamylation events, but this study shows that carbamylation of ubiquitin at specific sites can negatively regulate ubiquitin-mediated signaling. The study also found that half of the ubiquitin amines have a relatively low pKa, making them more susceptible to carbamylation under physiological conditions. These findings suggest a mechanism for CO2 levels to affect specific polyubiquitin-mediated signaling pathways.
Article
Genetics & Heredity
Randi Istrup Juul, Morten Muhlig Nielsen, Malene Juul, Lars Feuerbach, Jakob Skou Pedersen
Summary: This study utilized large sets of whole cancer genomes to study mutation hotspots, categorize site-specific hotspots, and provide a resource of annotated hotspots genome-wide. The research found an excess of hotspots in protein-coding and gene regulatory regions, as well as identified hotspots associated with cancer genes. Additionally, some hotspots showed clear signs of positive selection.
NPJ GENOMIC MEDICINE
(2021)
Article
Biochemistry & Molecular Biology
Bernhard Luscher, Ivan Ahel, Matthias Altmeyer, Alan Ashworth, Peter Bai, Paul Chang, Michael Cohen, Daniela Corda, Francoise Dantzer, Matthew D. Daugherty, Ted M. Dawson, Valina L. Dawson, Sebastian Deindl, Anthony R. Fehr, Karla L. H. Feijs, Dmitri V. Filippov, Jean-Philippe Gagne, Giovanna Grimaldi, Sebastian Guettler, Nicolas C. Hoch, Michael O. Hottiger, Patricia Korn, W. Lee Kraus, Andreas Ladurner, Lari Lehtio, Anthony K. L. Leung, Christopher J. Lord, Aswin Mangerich, Ivan Matic, Jason Matthews, George-Lucian Moldovan, Joel Moss, Gioacchino Natoli, Michael L. Nielsen, Mario Niepel, Friedrich Nolte, John Pascal, Bryce M. Paschal, Krzysztof Pawlowski, Guy G. Poirier, Susan Smith, Gyula Timinszky, Zhao-Qi Wang, Jose Yelamos, Xiaochun Yu, Roko Zaja, Mathias Ziegler
Summary: ADP-ribosylation, a post-translational modification of proteins, nucleic acids, and metabolites, plays diverse roles in cellular processes such as stress responses, signaling, and transcriptional regulation. Recent advances in research have identified a wide range of cellular pathways regulated by ADP-ribosylation, highlighting the importance of understanding this mechanism in cell biology.
Article
Biochemistry & Molecular Biology
Lisa Schubert, Ivo A. Hendriks, Emil P. T. Hertz, Wei Wu, Selene Selles-Baiget, Saskia Hoffmann, Keerthana Stine Viswalingam, Irene Gallina, Satyakrishna Pentakota, Bente Benedict, Joachim Johansen, Katja Apelt, Martijn S. Luijsterburg, Simon Rasmussen, Michael Lisby, Ying Liu, Michael L. Nielsen, Niels Mailand, Julien P. Duxin
Summary: This study reveals an essential role of SCAI in ensuring error-free ICL repair upon activation of the FA pathway. SCAI forms a complex with Pol zeta and localizes to ICLs during DNA replication. In the absence of SCAI, HR-mediated ICL repair is defective, resulting in deletions and radial chromosomes.
Article
Biotechnology & Applied Microbiology
Alberto Santos, Ana R. Colaco, Annelaura B. Nielsen, Lili Niu, Maximilian Strauss, Philipp E. Geyer, Fabian Coscia, Nicolai J. Wewer Albrechtsen, Filip Mundt, Lars Juhl Jensen, Matthias Mann
Summary: A knowledge graph platform integrates proteomics with other omics data and biomedical databases, providing support for precision medicine. The Clinical Knowledge Graph (CKG) is a flexible data model that can accommodate a large number of nodes and relationships, accelerating the analysis and interpretation of proteomics data. By incorporating CKG, clinical decision-making can be informed and proteomics data can be enriched.
NATURE BIOTECHNOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Xu Zhao, Ivo A. Hendriks, Stephanie Le Gras, Tao Ye, Lucia Ramos-Alonso, Aurelie Nguea P, Guro Flor Lien, Fatemeh Ghasemi, Arne Klungland, Bernard Jost, Jorrit M. Enserink, Michael L. Nielsen, Pierre Chymkowitch
Summary: Sumoylation pathway plays a crucial role in adipocyte differentiation, supporting both the establishment of mature adipocyte transcriptional program and rewiring of transcriptional networks.
NUCLEIC ACIDS RESEARCH
(2022)
Article
Microbiology
Haris Zafeiropoulos, Savvas Paragkamian, Stelios Ninidakis, Georgios A. Pavlopoulos, Lars Juhl Jensen, Evangelos Pafilis
Summary: PREGO is a comprehensive knowledge base that provides associations between what, where, and who through text mining and data integration techniques, assisting researchers in designing and interpreting experiments and their results.
Article
Neurosciences
Maria Hvidberg Petersen, Cecilie Wennemoes Willert, Jens Velde Andersen, Mette Madsen, Helle Sonderby Waagepetersen, Niels Henning Skotte, Anne Norremolle
Summary: This study reveals that synaptic mitochondria in the striatum are more severely affected by Huntington's disease pathology than those in the cortex, leading to increased oxygen consumption and mitochondrial proton leak of striatal synaptosomes.
JOURNAL OF HUNTINGTONS DISEASE
(2022)
Article
Multidisciplinary Sciences
Pietro Fontana, Sara C. Buch-Larsen, Osamu Suyari, Rebecca Smith, Marcin J. Suskiewicz, Kira Schutzenhofer, Antonio Ariza, Johannes Gregor Matthias Rack, Michael L. Nielsen, Ivan Ahel
Summary: ADP-ribosylation signalling plays a crucial role in the DNA damage response of mammals, and its mechanism in fruit flies has been established using a multidisciplinary approach. Ser-ADPr is the major form of ADP-ribosylation in the DNA damage response of Drosophila melanogaster, and its formation depends on the dParp1:dHpf1 complex. The findings suggest that fruit flies are valuable model organisms to study the physiological role of Ser-ADPr signalling.
NATURE COMMUNICATIONS
(2023)
Article
Biochemistry & Molecular Biology
Emil P. T. Hertz, Ignacio Alonso-de Vega, Thomas Kruse, Yiqing Wang, Ivo A. Hendriks, Anna H. Bizard, Ania Eugui-Anta, Ronald T. Hay, Michael L. Nielsen, Jakob Nilsson, Ian D. Hickson, Niels Mailand
Summary: Hertz et al. use CRISPR screening to identify genetic vulnerabilities to inhibition of SUMOylation in human cells. They show that SUMO exerts its essential role in cell proliferation via NIP45- and BTRR-PICH-mediated DNA catenane resolution pathways. NIP45 mediates a TOP2-independent DNA catenane resolution process through its SUMO-like domains, promoting SUMOylation of specific factors including the SLX4 multi-nuclease complex, which contributes to catenane conversion into DSBs. Their findings establish the importance of SUMOylation in enabling resolution of toxic DNA catenanes via non-epistatic NIP45- and BTRR-PICH-dependent pathways to prevent mitotic failure.
NATURE STRUCTURAL & MOLECULAR BIOLOGY
(2023)
Review
Biology
A. S. Rebak, I. A. Hendriks, M. L. Nielsen
Summary: Citrullination is an important post-translational modification of arginine, with roles in autoimmune disorders, innate immunity response, and stem cell potency maintenance. However, our understanding of citrullination is not as comprehensive as other post-translational modifications. High-resolution mass spectrometry provides an unbiased approach to study citrullination and has already provided valuable insights. There is still untapped potential for proteome-wide investigations of citrullination using mass spectrometry approaches.
PHILOSOPHICAL TRANSACTIONS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES
(2023)
Article
Multidisciplinary Sciences
Meeli Mullari, Nicolas Fossat, Niels H. Skotte, Andrea Asenjo-Martinez, David T. Humphreys, Jens Bukh, Agnete Kirkeby, Troels K. H. Scheel, Michael L. Nielsen
Summary: The authors present the Brain-pCLAP methodology, identify the RBP atlas of the mouse brain, and demonstrate the differential binding of the splicing factor RBM5 to Huntington's disease relevant transcripts in R6/2 mice. Overall, they provide insights into the role of RBPs in RNA processing and their association with neurodegeneration. Rating: 8 points.
NATURE COMMUNICATIONS
(2023)
Article
Multidisciplinary Sciences
Frederick Richards, Marta J. Llorca-Cardenosa, Jamie Langton, Sara C. Buch-Larsen, Noor F. Shamkhi, Abhishek Bharadwaj Sharma, Michael L. Nielsen, Nicholas D. Lakin
Summary: The authors identify that PARP1 maintains genome integrity by regulating replication fork recovery through break-induced replication. Mechanistically, this is achieved through MRE11-dependent PARP1 activation and site-specific ADP-ribosylation of PolD3. PARP1 and PARP2 also have a novel role in regulating Rad52-dependent replication fork repair, suppressing replication-associated DNA damage, and maintaining genome stability.
NATURE COMMUNICATIONS
(2023)