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2. Metabolism-driven in vitro/in vivo disconnect of an oral ERɑ VHL-PROTAC

Author

Hayhow, Thomas G., Williamson, Beth, Lawson, Mandy, Cureton, Natalie, Braybrooke, Erin L., Campbell, Andrew, Carbajo, Rodrigo J., Cheraghchi-Bashi, Azadeh, Chiarparin, Elisabetta, Diène, Coura R., Fallan, Charlene, Fisher, David I., Goldberg, Frederick W., Hopcroft, Lorna, Hopcroft, Philip, Jackson, Anne, Kettle, Jason G., Klinowska, Teresa, Künzel, Ulrike, Lamont, Gillian, Lewis, Hilary J., Maglennon, Gareth, Martin, Scott, Gutierrez, Pablo Morentin, Morrow, Christopher J., Nikolaou, Myria, Nissink, J. Willem M., O’Shea, Patrick, Polanski, Radoslaw, Schade, Markus, Scott, James S., Smith, Aaron, Weber, Judith, Wilson, Joanne, Yang, Bin, and Crafter, Claire

Published
2024
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6. Data from Preclinical Characterization of AZD9574, a Blood–Brain Barrier Penetrant Inhibitor of PARP1

Author

Staniszewska, Anna D., primary, Pilger, Domenic, primary, Gill, Sonja J., primary, Jamal, Kunzah, primary, Bohin, Natacha, primary, Guzzetti, Sofia, primary, Gordon, Jacob, primary, Hamm, Gregory, primary, Mundin, Gill, primary, Illuzzi, Giuditta, primary, Pike, Andy, primary, McWilliams, Lisa, primary, Maglennon, Gareth, primary, Rose, Jonathan, primary, Hawthorne, Glen, primary, Cortes Gonzalez, Miguel, primary, Halldin, Christer, primary, Johnström, Peter, primary, Schou, Magnus, primary, Critchlow, Susan E., primary, Fawell, Stephen, primary, Johannes, Jeffrey W., primary, Leo, Elisabetta, primary, Davies, Barry R., primary, Cosulich, Sabina, primary, Sarkaria, Jann N., primary, O'Connor, Mark J., primary, and Hamerlik, Petra, primary

Published
2024
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7. Supplementary Data 1 from Preclinical Characterization of AZD9574, a Blood–Brain Barrier Penetrant Inhibitor of PARP1

Author

Staniszewska, Anna D., primary, Pilger, Domenic, primary, Gill, Sonja J., primary, Jamal, Kunzah, primary, Bohin, Natacha, primary, Guzzetti, Sofia, primary, Gordon, Jacob, primary, Hamm, Gregory, primary, Mundin, Gill, primary, Illuzzi, Giuditta, primary, Pike, Andy, primary, McWilliams, Lisa, primary, Maglennon, Gareth, primary, Rose, Jonathan, primary, Hawthorne, Glen, primary, Cortes Gonzalez, Miguel, primary, Halldin, Christer, primary, Johnström, Peter, primary, Schou, Magnus, primary, Critchlow, Susan E., primary, Fawell, Stephen, primary, Johannes, Jeffrey W., primary, Leo, Elisabetta, primary, Davies, Barry R., primary, Cosulich, Sabina, primary, Sarkaria, Jann N., primary, O'Connor, Mark J., primary, and Hamerlik, Petra, primary

Published
2024
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8. Preclinical Characterization of AZD9574, a Blood–Brain Barrier Penetrant Inhibitor of PARP1

Author

Staniszewska, Anna D., primary, Pilger, Domenic, additional, Gill, Sonja J., additional, Jamal, Kunzah, additional, Bohin, Natacha, additional, Guzzetti, Sofia, additional, Gordon, Jacob, additional, Hamm, Gregory, additional, Mundin, Gill, additional, Illuzzi, Giuditta, additional, Pike, Andy, additional, McWilliams, Lisa, additional, Maglennon, Gareth, additional, Rose, Jonathan, additional, Hawthorne, Glen, additional, Cortes Gonzalez, Miguel, additional, Halldin, Christer, additional, Johnström, Peter, additional, Schou, Magnus, additional, Critchlow, Susan E., additional, Fawell, Stephen, additional, Johannes, Jeffrey W., additional, Leo, Elisabetta, additional, Davies, Barry R., additional, Cosulich, Sabina, additional, Sarkaria, Jann N., additional, O'Connor, Mark J., additional, and Hamerlik, Petra, additional

Published
2023
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9. The next-generation oral selective estrogen receptor degrader camizestrant (AZD9833) suppresses ER+ breast cancer growth and overcomes endocrine and CDK4/6 inhibitor resistance

Author

Lawson, Mandy, primary, Cureton, Natalie, additional, Ros, Susana, additional, Cheraghchi-Bashi-Astaneh, Azadeh, additional, Urosevic, Jelena, additional, D'Arcy, Sophie, additional, Delpuech, Oona, additional, DuPont, Michelle, additional, Fisher, David I., additional, Gangl, Eric T., additional, Lewis, Hilary, additional, Trueman, Dawn, additional, Wali, Neha, additional, Williamson, Stuart Charles., additional, Moss, Jennifer, additional, Montaudon, Elodie, additional, Derrien, Héloïse, additional, Marangoni, Elisabetta, additional, Miragaia, Ricardo J., additional, Gagrica, Sladjana, additional, Morentin Gutierrez, Pablo, additional, Moss, Thomas, additional, Maglennon, Gareth A., additional, Sutton, Daniel, additional, Polanski, Radoslaw, additional, Rosen, Alan, additional, Cairns, Jonathan, additional, Zhang, Pei, additional, Sánchez-Guixé, Mònica, additional, Serra, Violeta, additional, Critchlow, Susan E., additional, Scott, James S., additional, Lindemann, Justin P.O., additional, Barry, Simon T., additional, Klinowska, Teresa, additional, Morrow, Christopher J., additional, and Carnevalli, Larissa S., additional

Published
2023
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12. Supplementary Figure from Preclinical Characterization of AZD5305, A Next-Generation, Highly Selective PARP1 Inhibitor and Trapper

Author

Illuzzi, Giuditta, primary, Staniszewska, Anna D., primary, Gill, Sonja J., primary, Pike, Andy, primary, McWilliams, Lisa, primary, Critchlow, Susan E., primary, Cronin, Anna, primary, Fawell, Stephen, primary, Hawthorne, Glen, primary, Jamal, Kunzah, primary, Johannes, Jeffrey, primary, Leonard, Emilyanne, primary, Macdonald, Ruth, primary, Maglennon, Gareth, primary, Nikkilä, Jenni, primary, O'Connor, Mark J., primary, Smith, Aaron, primary, Southgate, Harriet, primary, Wilson, Joanne, primary, Yates, James, primary, Cosulich, Sabina, primary, and Leo, Elisabetta, primary

Published
2023
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13. Supplementary Data from Preclinical Characterization of AZD5305, A Next-Generation, Highly Selective PARP1 Inhibitor and Trapper

Author

Illuzzi, Giuditta, primary, Staniszewska, Anna D., primary, Gill, Sonja J., primary, Pike, Andy, primary, McWilliams, Lisa, primary, Critchlow, Susan E., primary, Cronin, Anna, primary, Fawell, Stephen, primary, Hawthorne, Glen, primary, Jamal, Kunzah, primary, Johannes, Jeffrey, primary, Leonard, Emilyanne, primary, Macdonald, Ruth, primary, Maglennon, Gareth, primary, Nikkilä, Jenni, primary, O'Connor, Mark J., primary, Smith, Aaron, primary, Southgate, Harriet, primary, Wilson, Joanne, primary, Yates, James, primary, Cosulich, Sabina, primary, and Leo, Elisabetta, primary

Published
2023
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14. Supplementary Data from Preclinical Comparison of the Blood–brain barrier Permeability of Osimertinib with Other EGFR TKIs

Author

Colclough, Nicola, primary, Chen, Kan, primary, Johnström, Peter, primary, Strittmatter, Nicole, primary, Yan, Yumei, primary, Wrigley, Gail L., primary, Schou, Magnus, primary, Goodwin, Richard, primary, Varnäs, Katarina, primary, Adua, Sally J., primary, Zhao, Minghui, primary, Nguyen, Don X., primary, Maglennon, Gareth, primary, Barton, Peter, primary, Atkinson, James, primary, Zhang, Lin, primary, Janefeldt, Annika, primary, Wilson, Joanne, primary, Smith, Aaron, primary, Takano, Akihiro, primary, Arakawa, Ryosuke, primary, Kondrashov, Mikhail, primary, Malmquist, Jonas, primary, Revunov, Evgeny, primary, Vazquez-Romero, Ana, primary, Moein, Mohammad Mahdi, primary, Windhorst, Albert D., primary, Karp, Natasha A., primary, Finlay, M. Raymond V., primary, Ward, Richard A., primary, Yates, James W.T., primary, Smith, Paul D., primary, Farde, Lars, primary, Cheng, Zack, primary, and Cross, Darren A.E., primary

Published
2023
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16. Figure S1 from Preclinical Comparison of the Blood–brain barrier Permeability of Osimertinib with Other EGFR TKIs

Author

Colclough, Nicola, primary, Chen, Kan, primary, Johnström, Peter, primary, Strittmatter, Nicole, primary, Yan, Yumei, primary, Wrigley, Gail L., primary, Schou, Magnus, primary, Goodwin, Richard, primary, Varnäs, Katarina, primary, Adua, Sally J., primary, Zhao, Minghui, primary, Nguyen, Don X., primary, Maglennon, Gareth, primary, Barton, Peter, primary, Atkinson, James, primary, Zhang, Lin, primary, Janefeldt, Annika, primary, Wilson, Joanne, primary, Smith, Aaron, primary, Takano, Akihiro, primary, Arakawa, Ryosuke, primary, Kondrashov, Mikhail, primary, Malmquist, Jonas, primary, Revunov, Evgeny, primary, Vazquez-Romero, Ana, primary, Moein, Mohammad Mahdi, primary, Windhorst, Albert D., primary, Karp, Natasha A., primary, Finlay, M. Raymond V., primary, Ward, Richard A., primary, Yates, James W.T., primary, Smith, Paul D., primary, Farde, Lars, primary, Cheng, Zack, primary, and Cross, Darren A.E., primary

Published
2023
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17. Targeted Desorption Electrospray Ionization Mass Spectrometry Imaging for Drug Distribution, Toxicity, and Tissue Classification Studies

Author

Dannhorn, Andreas, primary, Doria, Maria Luisa, additional, McKenzie, James, additional, Inglese, Paolo, additional, Swales, John G., additional, Hamm, Gregory, additional, Strittmatter, Nicole, additional, Maglennon, Gareth, additional, Ghaem-Maghami, Sadaf, additional, Goodwin, Richard J. A., additional, and Takats, Zoltan, additional

Published
2023
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20. Preclinical Characterization of AZD5305, A Next-Generation, Highly Selective PARP1 Inhibitor and Trapper

Author

Illuzzi, Giuditta, primary, Staniszewska, Anna D., additional, Gill, Sonja J., additional, Pike, Andy, additional, McWilliams, Lisa, additional, Critchlow, Susan E., additional, Cronin, Anna, additional, Fawell, Stephen, additional, Hawthorne, Glen, additional, Jamal, Kunzah, additional, Johannes, Jeffrey, additional, Leonard, Emilyanne, additional, Macdonald, Ruth, additional, Maglennon, Gareth, additional, Nikkilä, Jenni, additional, O'Connor, Mark J., additional, Smith, Aaron, additional, Southgate, Harriet, additional, Wilson, Joanne, additional, Yates, James, additional, Cosulich, Sabina, additional, and Leo, Elisabetta, additional

Published
2022
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21. Method To Visualize the Intratumor Distribution and Impact of Gemcitabine in Pancreatic Ductal Adenocarcinoma by Multimodal Imaging

Author

Strittmatter, Nicole, Richards, Frances M., Race, Alan M., Ling, Stephanie, Sutton, Daniel, Nilsson, Anna, Wallez, Yann, Barnes, Jennifer, Maglennon, Gareth, Gopinathan, Aarthi, Brais, Rebecca, Wong, Edmond, Serra, Maria Paola, Atkinson, James, Smith, Aaron, Wilson, Joanne, Hamm, Gregory, Johnson, Timothy, I, Dunlop, Charles R., Kaistha, Brajesh P., Bunch, Josephine, Sansom, Owen J., Takats, Zoltan, Andrén, Per E., Lau, Alan, Barry, Simon T., Goodwin, Richard J. A., Jodrell, Duncan, I, Strittmatter, Nicole, Richards, Frances M., Race, Alan M., Ling, Stephanie, Sutton, Daniel, Nilsson, Anna, Wallez, Yann, Barnes, Jennifer, Maglennon, Gareth, Gopinathan, Aarthi, Brais, Rebecca, Wong, Edmond, Serra, Maria Paola, Atkinson, James, Smith, Aaron, Wilson, Joanne, Hamm, Gregory, Johnson, Timothy, I, Dunlop, Charles R., Kaistha, Brajesh P., Bunch, Josephine, Sansom, Owen J., Takats, Zoltan, Andrén, Per E., Lau, Alan, Barry, Simon T., Goodwin, Richard J. A., and Jodrell, Duncan, I

Abstract

Gemcitabine (dFdC) is a common treatment for pancreatic cancer; however, it is thought that treatment may fail because tumor stroma prevents drug distribution to tumor cells. Gemcitabine is a pro-drug with active metabolites generated intracellularly; therefore, visualizing the distribution of parent drug as well as its metabolites is important. A multimodal imaging approach was developed using spatially coregistered mass spectrometry imaging (MSI), imaging mass cytometry (IMC), multiplex immunofluorescence microscopy (mIF), and hematoxylin and eosin (H&E) staining to assess the local distribution and metabolism of gemcitabine in tumors from a genetically engineered mouse model of pancreatic cancer (KPC) allowing for comparisons between effects in the tumor tissue and its microenvironment. Mass spectrometry imaging (MSI) enabled the visualization of the distribution of gemcitabine (100 mg/kg), its phosphorylated metabolites dFdCMP, dFdCDP and dFdCTP, and the inactive metabolite dFdU. Distribution was compared to small-molecule ATR inhibitor AZD6738 (25 mg/kg), which was codosed. Gemcitabine metabolites showed heterogeneous distribution within the tumor, which was different from the parent compound. The highest abundance of dFdCMP, dFdCDP, and dFdCTP correlated with distribution of endogenous AMP, ADP, and ATP in viable tumor cell regions, showing that gemcitabine active metabolites are reaching the tumor cell compartment, while AZD6738 was located to nonviable tumor regions. The method revealed that the generation of active, phosphorylated dFdC metabolites as well as treatment-induced DNA damage primarily correlated with sites of high proliferation in KPC PDAC tumor tissue, rather than sites of high parent drug abundance.

Published
2022
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23. Rationally designed mariner vectors for functional genomic analysis of Actinobacillus pleuropneumoniae and other Pasteurellaceae species by transposon-directed insertion-site sequencing (TraDIS)

Author

Bossé, Janine T, Li, Yanwen, Leanse, Leon G, Zhou, Liqing, Chaudhuri, Roy R, Peters, Sarah E, Wang, Jinhong, Maglennon, Gareth A, Holden, Matthew TG, Maskell, Duncan J, Tucker, Alexander W, Wren, Brendan W, Rycroft, Andrew N, Langford, Paul R, and BRaDP1T consortium

Abstract

Comprehensive identification of conditionally essential genes requires efficient tools for generating high-density transposon libraries that, ideally, can be analysed using next-generation sequencing methods such as Transposon Directed Insertion-site Sequencing (TraDIS). The Himar1 (mariner) transposon is ideal for generating near-saturating mutant libraries, especially in AT-rich chromosomes, as the requirement for integration is a TA dinucleotide, and this transposon has been used for mutagenesis of a wide variety of bacteria. However, plasmids for mariner delivery do not necessarily work well in all bacteria. In particular, there are limited tools for functional genomic analysis of Pasteurellaceae species of major veterinary importance, such as swine and cattle pathogens, Actinobacillus pleuropneumoniae and Pasteurella multocida, respectively. Here, we developed plasmids, pTsodCPC9 and pTlacPC9 (differing only in the promoter driving expression of the transposase gene), that allow delivery of mariner into both these pathogens, but which should also be applicable to a wider range of bacteria. Using the pTlacPC9 vector, we have generated, for the first time, saturating mariner mutant libraries in both A. pleuropneumoniae and P. multocida that showed a near random distribution of insertions around the respective chromosomes as detected by TraDIS. A preliminary screen of 5000 mutants each identified 8 and 14 genes, respectively, that are required for growth under anaerobic conditions. Future high-throughput screening of the generated libraries will facilitate identification of mutants required for growth under different conditions, including in vivo, highlighting key virulence factors and pathways that can be exploited for development of novel therapeutics and vaccines.

Published
2021

24. Method To Visualize the Intratumor Distribution and Impact of Gemcitabine in Pancreatic Ductal Adenocarcinoma by Multimodal Imaging

Author

Strittmatter, Nicole, primary, Richards, Frances M., additional, Race, Alan M., additional, Ling, Stephanie, additional, Sutton, Daniel, additional, Nilsson, Anna, additional, Wallez, Yann, additional, Barnes, Jennifer, additional, Maglennon, Gareth, additional, Gopinathan, Aarthi, additional, Brais, Rebecca, additional, Wong, Edmond, additional, Serra, Maria Paola, additional, Atkinson, James, additional, Smith, Aaron, additional, Wilson, Joanne, additional, Hamm, Gregory, additional, Johnson, Timothy I., additional, Dunlop, Charles R., additional, Kaistha, Brajesh P., additional, Bunch, Josephine, additional, Sansom, Owen J., additional, Takats, Zoltan, additional, Andrén, Per E., additional, Lau, Alan, additional, Barry, Simon T., additional, Goodwin, Richard J. A., additional, and Jodrell, Duncan I., additional

Published
2022
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25. Holistic Characterization of a Salmonella Typhimurium Infection Model Using Integrated Molecular Imaging

Author

Strittmatter, Nicole, primary, Kanvatirth, Panchali, additional, Inglese, Paolo, additional, Race, Alan M., additional, Nilsson, Anna, additional, Dannhorn, Andreas, additional, Kudo, Hiromi, additional, Goldin, Robert D., additional, Ling, Stephanie, additional, Wong, Edmond, additional, Seeliger, Frank, additional, Serra, Maria Paola, additional, Hoffmann, Scott, additional, Maglennon, Gareth, additional, Hamm, Gregory, additional, Atkinson, James, additional, Jones, Stewart, additional, Bunch, Josephine, additional, Andrén, Per E., additional, Takats, Zoltan, additional, Goodwin, Richard J. A., additional, and Mastroeni, Pietro, additional

Published
2021
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26. Identification of dfrA14 in two distinct plasmids conferring trimethoprim resistance in Actinobacillus pleuropneumoniae

Author

Bossé, Janine T., Li, Yanwen, Walker, Stephanie, Atherton, Tom, Fernandez Crespo, Roberto, Williamson, Susanna M., Rogers, Jon, Chaudhuri, Roy R., Weinert, Lucy A., Oshota, Olusegun, Holden, Matt T. G., Maskell, Duncan J., Tucker, Alexander W., Wren, Brendan W., Rycroft, Andrew N., Langford, Paul R., Maskell, Duncan J., (Dan) Tucker, Alexander W., Peters, Sarah E., Weinert, Lucy A., (Tracy) Wang, Jinhong, Luan, Shi-Lu, Chaudhuri, Roy R., Rycroft, Andrew N., Maglennon, Gareth A., Matthews, Dominic, Wren, Brendan W., Cuccui, Jon, Terra, Vanessa S., Langford, Paul R., Bossé, Janine T., and Li, Yanwen

Published
2015
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27. Abstract 1374: The novel PARP1-selective inhibitor AZD5305 has reduced hematological toxicity when compared to PARP1/2 inhibitors in pre-clinical models

Author

Gill, Sonja J., primary, Macdonald, Ruth, additional, Pin, Carmen, additional, Collins, Rob, additional, Leonard, Emilyanne, additional, Maglennon, Gareth, additional, Pike, Andy, additional, Cotton, Peter, additional, Hawthorne, Glen, additional, Pugh, Jordan, additional, Sargeant, Rebecca, additional, Sutton, Daniel, additional, Atkinson, James, additional, Jones, Stewart, additional, Chinery, Sarah, additional, and Anderton, Mark, additional

Published
2021
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28. Holistic Characterization of a Salmonella Typhimurium Infection Model Using Integrated Molecular Imaging

Author

Strittmatter, Nicole, Kanvatirth, Panchali, Inglese, Paolo, Race, Alan M., Nilsson, Anna, Dannhorn, Andreas, Kudo, Hiromi, Goldin, Robert D., Ling, Stephanie, Wong, Edmond, Seeliger, Frank, Serra, Maria Paola, Hoffmann, Scott, Maglennon, Gareth, Hamm, Gregory, Atkinson, James, Jones, Stewart, Bunch, Josephine, Andren, Per E., Takats, Zoltan, Goodwin, Richard J. A., Mastroeni, Pietro, Strittmatter, Nicole, Kanvatirth, Panchali, Inglese, Paolo, Race, Alan M., Nilsson, Anna, Dannhorn, Andreas, Kudo, Hiromi, Goldin, Robert D., Ling, Stephanie, Wong, Edmond, Seeliger, Frank, Serra, Maria Paola, Hoffmann, Scott, Maglennon, Gareth, Hamm, Gregory, Atkinson, James, Jones, Stewart, Bunch, Josephine, Andren, Per E., Takats, Zoltan, Goodwin, Richard J. A., and Mastroeni, Pietro

Abstract

A more complete and holistic view on host-microbe interactions is needed to understand the physiological and cellular barriers that affect the efficacy of drug treatments and allow the discovery and development of new therapeutics. Here, we developed a multimodal imaging approach combining histopathology with mass spectrometry imaging (MSI) and same section imaging mass cytometry (IMC) to study the effects of Salmonella Typhimurium infection in the liver of a mouse model using the S. Typhimurium strains SL3261 and SL1344. This approach enables correlation of tissue morphology and specific cell phenotypes with molecular images of tissue metabolism. IMC revealed a marked increase in immune cell markers and localization in immune aggregates in infected tissues. A correlative computational method (network analysis) was deployed to find metabolic features associated with infection and revealed metabolic clusters of acetyl carnitines, as well as phosphatidylcholine and phosphatidylethanolamine plasmalogen species, which could be associated with pro-inflammatory immune cell types. By developing an IMC marker for the detection of Salmonella LPS, we were further able to identify and characterize those cell types which contained S. Typhimurium.

Published
2021
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29. Method to Investigate the Distribution of Water-Soluble Drug-Delivery Systems in Fresh Frozen Tissues Using Imaging Mass Cytometry

Author

Strittmatter, Nicole, primary, England, Richard M., additional, Race, Alan M., additional, Sutton, Daniel, additional, Moss, Jennifer I., additional, Maglennon, Gareth, additional, Ling, Stephanie, additional, Wong, Edmond, additional, Rose, Jonathan, additional, Purvis, Ian, additional, Macdonald, Ruth, additional, Barry, Simon T., additional, Ashford, Marianne B., additional, and Goodwin, Richard J. A., additional

Published
2021
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30. Deep Learning-Based Annotation Transfer between Molecular Imaging Modalities: An Automated Workflow for Multimodal Data Integration

Author

Race, Alan M., primary, Sutton, Daniel, additional, Hamm, Gregory, additional, Maglennon, Gareth, additional, Morton, Jennifer P., additional, Strittmatter, Nicole, additional, Campbell, Andrew, additional, Sansom, Owen J., additional, Wang, Yinhai, additional, Barry, Simon T., additional, Takáts, Zoltan, additional, Goodwin, Richard J. A., additional, and Bunch, Josephine, additional

Published
2021
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31. Evaluation of UV-C Decontamination of Clinical Tissue Sections for Spatially Resolved Analysis by Mass Spectrometry Imaging (MSI)

Author

Dannhorn, Andreas, primary, Ling, Stephanie, additional, Powell, Steven, additional, McCall, Eileen, additional, Maglennon, Gareth, additional, Jones, Gemma N., additional, Pierce, Andrew J., additional, Strittmatter, Nicole, additional, Hamm, Gregory, additional, Barry, Simon T., additional, Bunch, Josephine, additional, Goodwin, Richard J. A., additional, and Takats, Zoltan, additional

Published
2021
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32. Preclinical Comparison of the Blood–brain barrier Permeability of Osimertinib with Other EGFR TKIs

Author

Colclough, Nicola, primary, Chen, Kan, additional, Johnström, Peter, additional, Strittmatter, Nicole, additional, Yan, Yumei, additional, Wrigley, Gail L., additional, Schou, Magnus, additional, Goodwin, Richard, additional, Varnäs, Katarina, additional, Adua, Sally J., additional, Zhao, Minghui, additional, Nguyen, Don X., additional, Maglennon, Gareth, additional, Barton, Peter, additional, Atkinson, James, additional, Zhang, Lin, additional, Janefeldt, Annika, additional, Wilson, Joanne, additional, Smith, Aaron, additional, Takano, Akihiro, additional, Arakawa, Ryosuke, additional, Kondrashov, Mikhail, additional, Malmquist, Jonas, additional, Revunov, Evgeny, additional, Vazquez-Romero, Ana, additional, Moein, Mohammad Mahdi, additional, Windhorst, Albert D., additional, Karp, Natasha A., additional, Finlay, M. Raymond V., additional, Ward, Richard A., additional, Yates, James W.T., additional, Smith, Paul D., additional, Farde, Lars, additional, Cheng, Zack, additional, and Cross, Darren A.E., additional

Published
2021
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33. Abstract 4379: Not all selective estrogen receptor degraders are equal - Preclinical comparison of AZD9833, AZD9496 and fulvestrant

Author

Lawson, Mandy, primary, Cureton, Natalie, additional, DuPont, Michelle, additional, Delpuech, Oona, additional, Trueman, Dawn, additional, Zhang, Pei, additional, Cheraghchi-Bashi-Astaneh, Azadeh, additional, Gagrica, Sladjana, additional, Maglennon, Gareth, additional, Sutton, Daniel, additional, Zhang, Bairu, additional, Cairns, Jonathan, additional, Scott, Jamie, additional, Klinowska, Teresa, additional, and Morrow, Christopher J., additional

Published
2020
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34. Universal Sample Preparation Unlocking Multimodal Molecular Tissue Imaging

Author

Dannhorn, Andreas, primary, Kazanc, Emine, additional, Ling, Stephanie, additional, Nikula, Chelsea, additional, Karali, Evdoxia, additional, Serra, Maria Paola, additional, Vorng, Jean-Luc, additional, Inglese, Paolo, additional, Maglennon, Gareth, additional, Hamm, Gregory, additional, Swales, John, additional, Strittmatter, Nicole, additional, Barry, Simon T., additional, Sansom, Owen J., additional, Poulogiannis, George, additional, Bunch, Josephine, additional, Goodwin, Richard JA, additional, and Takats, Zoltan, additional

Published
2020
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35. Abstract P6-04-15: Oral selective estrogen receptor degrader AZD9496 demonstrated preclinical model specific differences to fulvestrant in estrogen receptor degradation, agonism and anti-tumour effects

Author

Lawson, Mandy, primary, Cureton, Natalie, additional, Delpuech, Oona, additional, Zhang, Pei, additional, Cheraghchi-Bashi-Astaneh, Azadeh, additional, Gagrica, Sladjana, additional, Trueman, Dawn, additional, Maglennon, Gareth, additional, Sutton, Daniel, additional, Zhang, Bairu, additional, Cairns, Jonathan, additional, Klinowska, Teresa, additional, and Morrow, Christopher J, additional

Published
2020
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37. CON4EI: Bovine Corneal Opacity and Permeability (BCOP) test for hazard identification and labelling of eye irritating chemicals

Author

Verstraelen, Sandra, primary, Maglennon, Gareth, additional, Hollanders, Karen, additional, Boonen, Francis, additional, Adriaens, Els, additional, Alépée, Nathalie, additional, Drzewiecka, Agnieszka, additional, Gruszka, Katarzyna, additional, Kandarova, Helena, additional, Willoughby, Jamin A., additional, Guest, Robert, additional, Schofield, Jane, additional, and Van Rompay, An R., additional

Published
2017
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38. Development of a self-replicating plasmid system for Mycoplasma hyopneumoniae

Author

Maglennon, Gareth A, Cook, Beth S, Matthews, Dominic, Deeney, Alannah S, Bossé, Janine T, Langford, Paul R, Maskell, Duncan J, Tucker, Alexander W, Wren, Brendan W, Rycroft, Andrew N, and BRaDP1T consortium

Abstract

Mycoplasma hyopneumoniae is a prevalent swine respiratory pathogen that is a major cause of economic loss to pig producers. Control is achieved by a combination of antimicrobials, vaccination and management practices, but current vaccines offer only partial control and there is a need for improved preventative strategies. A major barrier to advances in understanding the pathogenesis of M. hyopneumoniae and in developing new vaccines is the lack of tools to genetically manipulate the organism. We describe the development and optimisation of the first successful plasmid-based system for the genetic manipulation of M. hyopneumoniae. Our artificial plasmids contain the origin of replication (oriC) of M. hyopneumoniae along with tetM, conferring resistance to tetracycline. With these plasmids, we have successfully transformed M. hyopneumoniae strain 232 by electroporation, generating tetracycline resistant organisms. The persistence of extrachromosomal plasmid and maintenance of plasmid DNA over serial passages shows that these artificial plasmids are capable of self-replication in M. hyopneumoniae. In addition to demonstrating the amenability of M. hyopneumoniae to genetic manipulation and in optimising the conditions necessary for successful transformation, we have used this system to determine the minimum functional oriC of M. hyopneumoniae. In doing so, we have developed a plasmid with a small oriC that is stably maintained over multiple passages that may be useful in generating targeted gene disruptions. In conclusion, we have generated a set of plasmids that will be valuable in studies of M. hyopneumoniae pathogenesis and provide a major step forward in the study of this important swine pathogen.

Published
2013

42. Rationally designed mariner vectors for functional genomic analysis of Actinobacillus pleuropneumoniae and other Pasteurellaceae species by transposon-directed insertion-site sequencing (TraDIS).

Author

Bossé JT, Li Y, Leanse LG, Zhou L, Chaudhuri RR, Peters SE, Wang J, Maglennon GA, Holden MTG, Maskell DJ, Tucker AW, Wren BW, Rycroft AN, and Langford PR

Abstract

Comprehensive identification of conditionally essential genes requires efficient tools for generating high-density transposon libraries that, ideally, can be analysed using next-generation sequencing methods such as Transposon Directed Insertion-site Sequencing (TraDIS). The Himar1 ( mariner ) transposon is ideal for generating near-saturating mutant libraries, especially in AT-rich chromosomes, as the requirement for integration is a TA dinucleotide, and this transposon has been used for mutagenesis of a wide variety of bacteria. However, plasmids for mariner delivery do not necessarily work well in all bacteria. In particular, there are limited tools for functional genomic analysis of Pasteurellaceae species of major veterinary importance, such as swine and cattle pathogens, Actinobacillus pleuropneumoniae and Pasteurella multocida , respectively. Here, we developed plasmids, pTsodCPC9 and pTlacPC9 (differing only in the promoter driving expression of the transposase gene), that allow delivery of mariner into both these pathogens, but which should also be applicable to a wider range of bacteria. Using the pTlacPC9 vector, we have generated, for the first time, saturating mariner mutant libraries in both A. pleuropneumoniae and  P. multocida that showed a near random distribution of insertions around the respective chromosomes as detected by TraDIS. A preliminary screen of 5000 mutants each identified 8 and 14 genes, respectively, that are required for growth under anaerobic conditions. Future high-throughput screening of the generated libraries will facilitate identification of mutants required for growth under different conditions, including in vivo , highlighting key virulence factors and pathways that can be exploited for development of novel therapeutics and vaccines., Competing Interests: Competing interestsAuthor Paul R. Langford was not involved in the journal’s review or decisions related to this manuscript. The authors declare no competing interests., (© The Author(s) 2021.)

Published
2021
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43. Development of a self-replicating plasmid system for Mycoplasma hyopneumoniae.

Author

Maglennon GA, Cook BS, Matthews D, Deeney AS, Bossé JT, Langford PR, Maskell DJ, Tucker AW, Wren BW, and Rycroft AN

Subjects
Animals, Bacterial Proteins metabolism, Mycoplasma hyopneumoniae immunology, Mycoplasma hyopneumoniae metabolism, Origin Recognition Complex metabolism, Plasmids metabolism, Swine, Bacterial Proteins genetics, Mycoplasma hyopneumoniae genetics, Origin Recognition Complex genetics, Plasmids genetics, Pneumonia of Swine, Mycoplasmal microbiology, Swine Diseases microbiology
Abstract

Mycoplasma hyopneumoniae is a prevalent swine respiratory pathogen that is a major cause of economic loss to pig producers. Control is achieved by a combination of antimicrobials, vaccination and management practices, but current vaccines offer only partial control and there is a need for improved preventative strategies. A major barrier to advances in understanding the pathogenesis of M. hyopneumoniae and in developing new vaccines is the lack of tools to genetically manipulate the organism. We describe the development and optimisation of the first successful plasmid-based system for the genetic manipulation of M. hyopneumoniae. Our artificial plasmids contain the origin of replication (oriC) of M. hyopneumoniae along with tetM, conferring resistance to tetracycline. With these plasmids, we have successfully transformed M. hyopneumoniae strain 232 by electroporation, generating tetracycline resistant organisms. The persistence of extrachromosomal plasmid and maintenance of plasmid DNA over serial passages shows that these artificial plasmids are capable of self-replication in M. hyopneumoniae. In addition to demonstrating the amenability of M. hyopneumoniae to genetic manipulation and in optimising the conditions necessary for successful transformation, we have used this system to determine the minimum functional oriC of M. hyopneumoniae. In doing so, we have developed a plasmid with a small oriC that is stably maintained over multiple passages that may be useful in generating targeted gene disruptions. In conclusion, we have generated a set of plasmids that will be valuable in studies of M. hyopneumoniae pathogenesis and provide a major step forward in the study of this important swine pathogen.

Published
2013
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