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Start Over Author "Balazs, P." Journal nature communications
32 results on '"Balazs, P."'

2. Enhancing antibody responses by multivalent antigen display on thymus-independent DNA origami scaffolds

Author

Eike-Christian Wamhoff, Larance Ronsard, Jared Feldman, Grant A. Knappe, Blake M. Hauser, Anna Romanov, James Brett Case, Shilpa Sanapala, Evan C. Lam, Kerri J. St. Denis, Julie Boucau, Amy K. Barczak, Alejandro B. Balazs, Michael S. Diamond, Aaron G. Schmidt, Daniel Lingwood, and Mark Bathe

Subjects
Science
Abstract

Abstract Protein-based virus-like particles (P-VLPs) are commonly used to spatially organize antigens and enhance humoral immunity through multivalent antigen display. However, P-VLPs are thymus-dependent antigens that are themselves immunogenic and can induce B cell responses that may neutralize the platform. Here, we investigate thymus-independent DNA origami as an alternative material for multivalent antigen display using the receptor binding domain (RBD) of the SARS-CoV-2 spike protein, the primary target of neutralizing antibody responses. Sequential immunization of mice with DNA-based VLPs (DNA-VLPs) elicits protective neutralizing antibodies to SARS-CoV-2 in a manner that depends on the valency of the antigen displayed and on T cell help. Importantly, the immune sera do not contain boosted, class-switched antibodies against the DNA scaffold, in contrast to P-VLPs that elicit strong B cell memory against both the target antigen and the scaffold. Thus, DNA-VLPs enhance target antigen immunogenicity without generating scaffold-directed immunity and thereby offer an important alternative material for particulate vaccine design.

Published
2024
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3. Design and structural validation of peptide–drug conjugate ligands of the kappa-opioid receptor

Author

Edin Muratspahić, Kristine Deibler, Jianming Han, Nataša Tomašević, Kirtikumar B. Jadhav, Aina-Leonor Olivé-Marti, Nadine Hochrainer, Roland Hellinger, Johannes Koehbach, Jonathan F. Fay, Mohammad Homaidur Rahman, Lamees Hegazy, Timothy W. Craven, Balazs R. Varga, Gaurav Bhardwaj, Kevin Appourchaux, Susruta Majumdar, Markus Muttenthaler, Parisa Hosseinzadeh, David J. Craik, Mariana Spetea, Tao Che, David Baker, and Christian W. Gruber

Subjects
Science
Abstract

Abstract Despite the increasing number of GPCR structures and recent advances in peptide design, the development of efficient technologies allowing rational design of high-affinity peptide ligands for single GPCRs remains an unmet challenge. Here, we develop a computational approach for designing conjugates of lariat-shaped macrocyclized peptides and a small molecule opioid ligand. We demonstrate its feasibility by discovering chemical scaffolds for the kappa-opioid receptor (KOR) with desired pharmacological activities. The designed De Novo Cyclic Peptide (DNCP)-β-naloxamine (NalA) exhibit in vitro potent mixed KOR agonism/mu-opioid receptor (MOR) antagonism, nanomolar binding affinity, selectivity, and efficacy bias at KOR. Proof-of-concept in vivo efficacy studies demonstrate that DNCP-β-NalA(1) induces a potent KOR-mediated antinociception in male mice. The high-resolution cryo-EM structure (2.6 Å) of the DNCP-β-NalA–KOR–Gi1 complex and molecular dynamics simulations are harnessed to validate the computational design model. This reveals a network of residues in ECL2/3 and TM6/7 controlling the intrinsic efficacy of KOR. In general, our computational de novo platform overcomes extensive lead optimization encountered in ultra-large library docking and virtual small molecule screening campaigns and offers innovation for GPCR ligand discovery. This may drive the development of next-generation therapeutics for medical applications such as pain conditions.

Published
2023
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4. Design and structural validation of peptide–drug conjugate ligands of the kappa-opioid receptor

Author

Muratspahić, Edin, Deibler, Kristine, Han, Jianming, Tomašević, Nataša, Jadhav, Kirtikumar B., Olivé-Marti, Aina-Leonor, Hochrainer, Nadine, Hellinger, Roland, Koehbach, Johannes, Fay, Jonathan F., Rahman, Mohammad Homaidur, Hegazy, Lamees, Craven, Timothy W., Varga, Balazs R., Bhardwaj, Gaurav, Appourchaux, Kevin, Majumdar, Susruta, Muttenthaler, Markus, Hosseinzadeh, Parisa, Craik, David J., Spetea, Mariana, Che, Tao, Baker, David, and Gruber, Christian W.

Published
2023
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5. Candida expansion in the gut of lung cancer patients associates with an ecological signature that supports growth under dysbiotic conditions

Author

Seelbinder, Bastian, Lohinai, Zoltan, Vazquez-Uribe, Ruben, Brunke, Sascha, Chen, Xiuqiang, Mirhakkak, Mohammad, Lopez-Escalera, Silvia, Dome, Balazs, Megyesfalvi, Zsolt, Berta, Judit, Galffy, Gabriella, Dulka, Edit, Wellejus, Anja, Weiss, Glen J., Bauer, Michael, Hube, Bernhard, Sommer, Morten O. A., and Panagiotou, Gianni

Published
2023
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6. Candida expansion in the gut of lung cancer patients associates with an ecological signature that supports growth under dysbiotic conditions

Author

Bastian Seelbinder, Zoltan Lohinai, Ruben Vazquez-Uribe, Sascha Brunke, Xiuqiang Chen, Mohammad Mirhakkak, Silvia Lopez-Escalera, Balazs Dome, Zsolt Megyesfalvi, Judit Berta, Gabriella Galffy, Edit Dulka, Anja Wellejus, Glen J. Weiss, Michael Bauer, Bernhard Hube, Morten O. A. Sommer, and Gianni Panagiotou

Subjects
Science
Abstract

Abstract Candida species overgrowth in the human gut is considered a prerequisite for invasive candidiasis, but our understanding of gut bacteria promoting or restricting this overgrowth is still limited. By integrating cross-sectional mycobiome and shotgun metagenomics data from the stool of 75 male and female cancer patients at risk but without systemic candidiasis, bacterial communities in high Candida samples display higher metabolic flexibility yet lower contributional diversity than those in low Candida samples. We develop machine learning models that use only bacterial taxa or functional relative abundances to predict the levels of Candida genus and species in an external validation cohort with an AUC of 78.6–81.1%. We propose a mechanism for intestinal Candida overgrowth based on an increase in lactate-producing bacteria, which coincides with a decrease in bacteria that regulate short chain fatty acid and oxygen levels. Under these conditions, the ability of Candida to harness lactate as a nutrient source may enable Candida to outcompete other fungi in the gut.

Published
2023
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7. Maternal immune response and placental antibody transfer after COVID-19 vaccination across trimester and platforms

Author

Caroline G. Atyeo, Lydia L. Shook, Sara Brigida, Rose M. De Guzman, Stepan Demidkin, Cordelia Muir, Babatunde Akinwunmi, Arantxa Medina Baez, Maegan L. Sheehan, Erin McSweeney, Madeleine D. Burns, Ruhi Nayak, Maya K. Kumar, Chinmay D. Patel, Allison Fialkowski, Dana Cvrk, Ilona T. Goldfarb, Lael M. Yonker, Alessio Fasano, Alejandro B. Balazs, Michal A. Elovitz, Kathryn J. Gray, Galit Alter, and Andrea G. Edlow

Subjects
Science
Abstract

Pregnant individuals infected with SARS-CoV-2 are at high risk of morbidity and mortality, in addition to adverse pregnancy outcomes, yet little is known regarding trimester-specific immunity and maternal protection from COVID-19 vaccine platforms. Authors utilise a systems serology approach to characterise the material antibody response and the transplacental antibody transfer, dependent on vaccine platform and trimester of vaccination.

Published
2022
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8. Signal requirement for cortical potential of transplantable human neuroepithelial stem cells

Author

Balazs V. Varga, Maryam Faiz, Helena Pivonkova, Gabriel Khelifi, Huijuan Yang, Shangbang Gao, Emma Linderoth, Mei Zhen, Ragnhildur Thora Karadottir, Samer M. Hussein, and Andras Nagy

Subjects
Science
Abstract

The regulatory pathways that control the human neural progenitor cell pool are not well understood. Here, Varga et al. identify signals that control the division of human pluripotent stem cell derived neural stem cells and their ability to make cortical neurons and glia.

Published
2022
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9. Computer modeling reveals modalities to actuate mutable, active matter

Author

Abhrajit Laskar, Raj Kumar Manna, Oleg E. Shklyaev, and Anna C. Balazs

Subjects
Science
Abstract

Catalytic reactions on flexible sheets generate fluid flows that transform the shape of the sheet, which in turn modifies the flow. These complex interactions make computer models vital for designing and harnessing these feedback loops to create soft active matter that autonomously performs self-sustained mechanical work.

Published
2022
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11. Multi-modal profiling of human fetal liver hematopoietic stem cells reveals the molecular signature of engraftment

Author

Vanuytsel, Kim, Villacorta-Martin, Carlos, Lindstrom-Vautrin, Jonathan, Wang, Zhe, Garcia-Beltran, Wilfredo F., Vrbanac, Vladimir, Parsons, Dylan, Lam, Evan C., Matte, Taylor M., Dowrey, Todd W., Kumar, Sara S., Li, Mengze, Wang, Feiya, Yeung, Anthony K., Mostoslavsky, Gustavo, Dries, Ruben, Campbell, Joshua D., Belkina, Anna C., Balazs, Alejandro B., and Murphy, George J.

Published
2022
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12. Maternal immune response and placental antibody transfer after COVID-19 vaccination across trimester and platforms

Author

Atyeo, Caroline G., Shook, Lydia L., Brigida, Sara, De Guzman, Rose M., Demidkin, Stepan, Muir, Cordelia, Akinwunmi, Babatunde, Baez, Arantxa Medina, Sheehan, Maegan L., McSweeney, Erin, Burns, Madeleine D., Nayak, Ruhi, Kumar, Maya K., Patel, Chinmay D., Fialkowski, Allison, Cvrk, Dana, Goldfarb, Ilona T., Yonker, Lael M., Fasano, Alessio, Balazs, Alejandro B., Elovitz, Michal A., Gray, Kathryn J., Alter, Galit, and Edlow, Andrea G.

Published
2022
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13. A systems genomics approach to uncover patient-specific pathogenic pathways and proteins in ulcerative colitis

Author

Brooks-Warburton, Johanne, Modos, Dezso, Sudhakar, Padhmanand, Madgwick, Matthew, Thomas, John P., Bohar, Balazs, Fazekas, David, Zoufir, Azedine, Kapuy, Orsolya, Szalay-Beko, Mate, Verstockt, Bram, Hall, Lindsay J., Watson, Alastair, Tremelling, Mark, Parkes, Miles, Vermeire, Severine, Bender, Andreas, Carding, Simon R., and Korcsmaros, Tamas

Published
2022
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15. A systems genomics approach to uncover patient-specific pathogenic pathways and proteins in ulcerative colitis

Author

Johanne Brooks-Warburton, Dezso Modos, Padhmanand Sudhakar, Matthew Madgwick, John P. Thomas, Balazs Bohar, David Fazekas, Azedine Zoufir, Orsolya Kapuy, Mate Szalay-Beko, Bram Verstockt, Lindsay J. Hall, Alastair Watson, Mark Tremelling, Miles Parkes, Severine Vermeire, Andreas Bender, Simon R. Carding, and Tamas Korcsmaros

Subjects
Science
Abstract

Single Nucleotide Polymorphisms (SNPs) affect cellular regulatory networks, and SNP co-occurrences contribute to disease pathogenesis in ulcerative colitis (UC). Here the authors introduce iSNP, a precision medicine pipeline that combines genomics and network biology approaches to uncover patient specific pathways affected in complex diseases.

Published
2022
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16. Multi-modal profiling of human fetal liver hematopoietic stem cells reveals the molecular signature of engraftment

Author

Kim Vanuytsel, Carlos Villacorta-Martin, Jonathan Lindstrom-Vautrin, Zhe Wang, Wilfredo F. Garcia-Beltran, Vladimir Vrbanac, Dylan Parsons, Evan C. Lam, Taylor M. Matte, Todd W. Dowrey, Sara S. Kumar, Mengze Li, Feiya Wang, Anthony K. Yeung, Gustavo Mostoslavsky, Ruben Dries, Joshua D. Campbell, Anna C. Belkina, Alejandro B. Balazs, and George J. Murphy

Subjects
Science
Abstract

During human embryonic development, haematopoietic stem cells of the foetal liver undergo expansion, while retaining engraftment capacity. Here the authors apply CITE-seq to profile single cells from a human foetal liver, identifying a molecular signature of engraftment potential

Published
2022
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17. Unwinding of a DNA replication fork by a hexameric viral helicase

Author

Abid Javed, Balazs Major, Jonathan A. Stead, Cyril M. Sanders, and Elena V. Orlova

Subjects
Science
Abstract

Replicative hexameric helicases are fundamental components of replisomes. Here the authors resolve a cryo-EM structure of the E1 helicase from papillomavirus bound to a DNA replication fork, providing insights into the mechanism of DNA unwinding by these hexameric enzymes.

Published
2021
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18. Triggering typical nemaline myopathy with compound heterozygous nebulin mutations reveals myofilament structural changes as pathomechanism

Author

Johan Lindqvist, Weikang Ma, Frank Li, Yaeren Hernandez, Justin Kolb, Balazs Kiss, Paola Tonino, Robbert van der Pijl, Esmat Karimi, Henry Gong, Josh Strom, Zaynab Hourani, John E. Smith, Coen Ottenheijm, Thomas Irving, and Henk Granzier

Subjects
Science
Abstract

Nebulin-based nemaline myopathy is a heterogenous disease with unclear pathological mechanisms. Here, the authors generate a mouse model that mimics the most common genetic cause of the disease and demonstrate that muscle weakness in this model is associated with twisted actin filaments and altered tropomyosin and troponin behaviour.

Published
2020
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20. An open source automated tumor infiltrating lymphocyte algorithm for prognosis in melanoma

Author

Balazs Acs, Fahad Shabbir Ahmed, Swati Gupta, Pok Fai Wong, Robyn D. Gartrell, Jaya Sarin Pradhan, Emanuelle M. Rizk, Bonnie Gould Rothberg, Yvonne M. Saenger, and David L. Rimm

Subjects
Science
Abstract

Histology data exists for many cancer samples and the ability to automatically image this data may provide prognostic information. Here, the authors generated an algorithm to measure tumour infiltrating lymphocytes in melanoma histology specimens and show that the ratio of these immune cells to tumour cells has prognostic value.

Published
2019
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21. Context-dependent limb movement encoding in neuronal populations of motor cortex

Author

Wolfgang Omlor, Anna-Sophia Wahl, Pia Sipilä, Henry Lütcke, Balazs Laurenczy, I-Wen Chen, Lazar T. Sumanovski, Marcel van ’t Hoff, Philipp Bethge, Fabian F. Voigt, Martin E. Schwab, and Fritjof Helmchen

Subjects
Science
Abstract

Network activity in primary motor cortex (M1) controls dexterous limb movements. Here, the authors show that the M1 population code varies according to contextual motor demands that are conveyed via the secondary motor cortex (M2).

Published
2019
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22. Mechanism of copper-free Sonogashira reaction operates through palladium-palladium transmetallation

Author

Martin Gazvoda, Miha Virant, Balazs Pinter, and Janez Košmrlj

Subjects
Science
Abstract

Although the Sonogashira coupling of acetylenes and vinyl/aryl halides has been applied for decades, many mechanistic questions have remained unanswered. Here, the authors provide experimental and theoretical support for two interlinked palladium cycles operating in the debated Sonogashira coupling mechanism.

Published
2018
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23. Understanding 6th-century barbarian social organization and migration through paleogenomics

Author

Carlos Eduardo G. Amorim, Stefania Vai, Cosimo Posth, Alessandra Modi, István Koncz, Susanne Hakenbeck, Maria Cristina La Rocca, Balazs Mende, Dean Bobo, Walter Pohl, Luisella Pejrani Baricco, Elena Bedini, Paolo Francalacci, Caterina Giostra, Tivadar Vida, Daniel Winger, Uta von Freeden, Silvia Ghirotto, Martina Lari, Guido Barbujani, Johannes Krause, David Caramelli, Patrick J. Geary, and Krishna R. Veeramah

Subjects
Science
Abstract

The Longobards invaded and conquered much of Italy after the fall of the Western Roman Empire. Here, the authors sequence and analyze ancient genomic DNA from 63 samples from two cemeteries associated with the Longobards and identify kinship networks and two distinct genetic and cultural groups in each.

Published
2018
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24. Intelligent image-based in situ single-cell isolation

Author

Csilla Brasko, Kevin Smith, Csaba Molnar, Nora Farago, Lili Hegedus, Arpad Balind, Tamas Balassa, Abel Szkalisity, Farkas Sukosd, Katalin Kocsis, Balazs Balint, Lassi Paavolainen, Marton Z. Enyedi, Istvan Nagy, Laszlo G. Puskas, Lajos Haracska, Gabor Tamas, and Peter Horvath

Subjects
Science
Abstract

The isolation of single cells while retaining context is important for quantifying cellular heterogeneity but technically challenging. Here, the authors develop a high-throughput, scalable workflow for microscopy-based single cell isolation using machine-learning, high-throughput microscopy and laser capture microdissection.

Published
2018
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25. Binding to SMN2 pre-mRNA-protein complex elicits specificity for small molecule splicing modifiers

Author

Manaswini Sivaramakrishnan, Kathleen D. McCarthy, Sébastien Campagne, Sylwia Huber, Sonja Meier, Angélique Augustin, Tobias Heckel, Hélène Meistermann, Melanie N. Hug, Pascale Birrer, Ahmed Moursy, Sarah Khawaja, Roland Schmucki, Nikos Berntenis, Nicolas Giroud, Sabrina Golling, Manuel Tzouros, Balazs Banfai, Gonzalo Duran-Pacheco, Jens Lamerz, Ying Hsiu Liu, Thomas Luebbers, Hasane Ratni, Martin Ebeling, Antoine Cléry, Sergey Paushkin, Adrian R. Krainer, Frédéric H.-T. Allain, and Friedrich Metzger

Subjects
Science
Abstract

Small molecules correcting the splicing deficit of the survival of motor neuron 2 (SMN2) gene have been identified as having therapeutic potential. Here, the authors provide evidence that SMN2 mRNA forms a ribonucleoprotein complex that can be specifically targeted by these small molecules.

Published
2017
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28. The giant protein titin regulates the length of the striated muscle thick filament

Author

Paola Tonino, Balazs Kiss, Josh Strom, Mei Methawasin, John E. Smith, Justin Kolb, Siegfried Labeit, and Henk Granzier

Subjects
Science
Abstract

Thick filaments in skeletal muscle and heart are composed of myosin. The authors show that the length of thick filaments is defined by titin, and that alterations in titin length affect force generation and lead to dilated cardiomyopathy in mice.

Published
2017
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29. Harnessing catalytic pumps for directional delivery of microparticles in microchambers

Author

Sambeeta Das, Oleg E. Shklyaev, Alicia Altemose, Henry Shum, Isamar Ortiz-Rivera, Lyanne Valdez, Thomas E. Mallouk, Anna C. Balazs, and Ayusman Sen

Subjects
Science
Abstract

Targeted delivery of microparticles is desirable for rapid, sensitive biological assays or self-assembly process. Here Daset al. use catalytic reactions on the surface of microfluidic chambers to generate unidirectional flows that carry and deposit microparticles to selective regions of the chamber.

Published
2017
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32. Understanding 6th-century barbarian social organization and migration through paleogenomics

Author

Amorim, Carlos Eduardo G., Vai, Stefania, Posth, Cosimo, Modi, Alessandra, Koncz, István, Hakenbeck, Susanne, La Rocca, Maria Cristina, Mende, Balazs, Bobo, Dean, Pohl, Walter, Baricco, Luisella Pejrani, Bedini, Elena, Francalacci, Paolo, Giostra, Caterina, Vida, Tivadar, Winger, Daniel, von Freeden, Uta, Ghirotto, Silvia, Lari, Martina, Barbujani, Guido, Krause, Johannes, Caramelli, David, Geary, Patrick J., and Veeramah, Krishna R.

Published
2018
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