A roadmap to generate renewable protein binders to the human proteome
- Colwill, Karen, Persson, Helena, Jarvik, Nicholas, Wyrzucki, Arkadiusz, Wojcik, John, Koide, Akiko, Kossiakoff, Anthony, Koide, Shohei, Sidhu, Sachdev, Dyson, Michael, Pershad, Kritika, Pavlovic, John, Karatt-Vellatt, Aneesh, Schofield, Darren, Kay, Brian, McCafferty, John, Mersmann, Michael, Meier, Doris, Mersmann, Jana, Helmsing, Saskia, Hust, Michael, Dubel, Stefan, Berkowicz, Susan, Freemantle, Alexia, Spiegel, Michael, Sawyer, Alan, Layton, Daniel, Nice, Edouard, Dai, Anna, Rocks, Oliver, Williton, Kelly, Fellouse, Frederic, Hersi, Kadija, Pawson, Tony, Nilsson, Peter, Sundberg, Marten, Sjoberg, Ronald, Sivertsson, Asa, Schwenk, Jochen, Takanen, Jenny, Hober, Sophia, Uhlen, Mathias, Dahlgren, Lars-Goran, Flores, Alex, Johansson, Ida, Weigelt, Johan, Crombet, Lissette, Loppnau, Peter, Kozieradzki, Ivona, Cossar, Doug, Arrowsmith, C., Edwards, Aled, Graslund, Susanne
- Authors: Colwill, Karen , Persson, Helena , Jarvik, Nicholas , Wyrzucki, Arkadiusz , Wojcik, John , Koide, Akiko , Kossiakoff, Anthony , Koide, Shohei , Sidhu, Sachdev , Dyson, Michael , Pershad, Kritika , Pavlovic, John , Karatt-Vellatt, Aneesh , Schofield, Darren , Kay, Brian , McCafferty, John , Mersmann, Michael , Meier, Doris , Mersmann, Jana , Helmsing, Saskia , Hust, Michael , Dubel, Stefan , Berkowicz, Susan , Freemantle, Alexia , Spiegel, Michael , Sawyer, Alan , Layton, Daniel , Nice, Edouard , Dai, Anna , Rocks, Oliver , Williton, Kelly , Fellouse, Frederic , Hersi, Kadija , Pawson, Tony , Nilsson, Peter , Sundberg, Marten , Sjoberg, Ronald , Sivertsson, Asa , Schwenk, Jochen , Takanen, Jenny , Hober, Sophia , Uhlen, Mathias , Dahlgren, Lars-Goran , Flores, Alex , Johansson, Ida , Weigelt, Johan , Crombet, Lissette , Loppnau, Peter , Kozieradzki, Ivona , Cossar, Doug , Arrowsmith, C. , Edwards, Aled , Graslund, Susanne
- Date: 2011
- Type: Text , Journal article
- Relation: Nature Methods Vol. 8, no. 7 (2011), p. 551-558
- Full Text: false
- Reviewed:
- Description: Despite the wealth of commercially available antibodies to human proteins, research is often hindered by their inconsistent validation, their poor performance and the inadequate coverage of the proteome. These issues could be addressed by systematic, genome-wide efforts to generate and validate renewable protein binders. We report a multicenter study to assess the potential of hybridoma and phage-display technologies in a coordinated large-scale antibody generation and validation effort. We produced over 1,000 antibodies targeting 20 SH2 domain proteins and evaluated them for potency and specificity by enzyme-linked immunosorbent assay (ELISA), protein microarray and surface plasmon resonance (SPR). We also tested selected antibodies in immunoprecipitation, immunoblotting and immunofluorescence assays. Our results show that high-affinity, high-specificity renewable antibodies generated by different technologies can be produced quickly and efficiently. We believe that this work serves as a foundation and template for future larger-scale studies to create renewable protein binders.
- Authors: Zhang, Jiapu
- Date: 2018
- Type: Text , Book
- Relation: Focus on Structral Biology Vol. 10
- Full Text: false
- Reviewed:
- Description: Unlike bacteria and viruses, which are based on DNA and RNA, prions are unique as disease-causing agents since they are misfolded proteins. Prion diseases are called "protein structural conformational diseases. This monograph is the book on molecular dynamics (MD) simulations nearly for all the known normal prion protein (PrPC) PDB entries in the Protein Data Bank (PDB) and associations. Pig is a species that is largely resistant to prions, and chicken, turtles, frogs are species resisting prion infection too firstly, this book will address all PrP strong immunity species (such as rabbits, dogs, horses, water buffaloes, pigs, chicken, turtles, frogs), compared with high susceptibility species. Other PrP models and doppel models are also MD studied in this book. Secondly, all the mutants of mouse PrP and human PrP are well studied by this book. Mouse mutations in the 2-2 loop and the C-terminal will bring clear structures with highly and clearly ordered loop structures. Human mutations will cause prion diseases such as Creutzfeldt-Jakob diseases (CJDs), Gerstmann-Sträussler-Scheinker (GSS) syndrome, fatal familial insomnia (FFI), etc. Deep MD analyses of mouse and human mutants are done in this book. Thirdly, PrP binding with antibodies/compounds etc. is well MD studied in this book. The informatics of potential antiprion drugs known will be revealed. Lastly, cross- structure PrP peptides are well studied. This book is ideal for practical computing staff in the fields of computational physics, computational biology, computational chemistry, biomedicine, bioinformatics, cheminformatics, materials, applied mathematics and theoretical physics, information technology, operations research, biostatistics, etc. As an accessible introduction to these fields, this book is also ideal as a teaching material for students.
A new era of integration between multiomics and spatio-temporal analysis for the translation of EMT towards clinical applications in cancer
- Fonseca Teixeira, Adilson, Wu, Siqi, Luwor, Rodney, Zhu, Hong-Jian
- Authors: Fonseca Teixeira, Adilson , Wu, Siqi , Luwor, Rodney , Zhu, Hong-Jian
- Date: 2023
- Type: Text , Journal article , Review
- Relation: Cells Vol. 12, no. 23 (2023), p.
- Full Text:
- Reviewed:
- Description: Epithelial-mesenchymal transition (EMT) is crucial to metastasis by increasing cancer cell migration and invasion. At the cellular level, EMT-related morphological and functional changes are well established. At the molecular level, critical signaling pathways able to drive EMT have been described. Yet, the translation of EMT into efficient diagnostic methods and anti-metastatic therapies is still missing. This highlights a gap in our understanding of the precise mechanisms governing EMT. Here, we discuss evidence suggesting that overcoming this limitation requires the integration of multiple omics, a hitherto neglected strategy in the EMT field. More specifically, this work summarizes results that were independently obtained through epigenomics/transcriptomics while comprehensively reviewing the achievements of proteomics in cancer research. Additionally, we prospect gains to be obtained by applying spatio-temporal multiomics in the investigation of EMT-driven metastasis. Along with the development of more sensitive technologies, the integration of currently available omics, and a look at dynamic alterations that regulate EMT at the subcellular level will lead to a deeper understanding of this process. Further, considering the significance of EMT to cancer progression, this integrative strategy may enable the development of new and improved biomarkers and therapeutics capable of increasing the survival and quality of life of cancer patients. © 2023 by the authors.
- Authors: Fonseca Teixeira, Adilson , Wu, Siqi , Luwor, Rodney , Zhu, Hong-Jian
- Date: 2023
- Type: Text , Journal article , Review
- Relation: Cells Vol. 12, no. 23 (2023), p.
- Full Text:
- Reviewed:
- Description: Epithelial-mesenchymal transition (EMT) is crucial to metastasis by increasing cancer cell migration and invasion. At the cellular level, EMT-related morphological and functional changes are well established. At the molecular level, critical signaling pathways able to drive EMT have been described. Yet, the translation of EMT into efficient diagnostic methods and anti-metastatic therapies is still missing. This highlights a gap in our understanding of the precise mechanisms governing EMT. Here, we discuss evidence suggesting that overcoming this limitation requires the integration of multiple omics, a hitherto neglected strategy in the EMT field. More specifically, this work summarizes results that were independently obtained through epigenomics/transcriptomics while comprehensively reviewing the achievements of proteomics in cancer research. Additionally, we prospect gains to be obtained by applying spatio-temporal multiomics in the investigation of EMT-driven metastasis. Along with the development of more sensitive technologies, the integration of currently available omics, and a look at dynamic alterations that regulate EMT at the subcellular level will lead to a deeper understanding of this process. Further, considering the significance of EMT to cancer progression, this integrative strategy may enable the development of new and improved biomarkers and therapeutics capable of increasing the survival and quality of life of cancer patients. © 2023 by the authors.
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