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- Author:
- David A. Tirrell, et al. ; Katharine Y. Fang; Seth A. Lieblich; Show all 3 Authors
- Source:
- Journal of polymer science 2019 v.57 no.3 pp. 264-267
- ISSN:
- 0887-624X
- Subject:
- dissociation; engineering; insulin; mutagenesis; pipecolic acid; polymers; proline; therapeutics
- Abstract:
- ... Non‐canonical amino acid mutagenesis was used to examine the biophysical consequences of changing ring size and structure at the single proline site in insulin. Addition of a methylene spacer to the prolyl ring (by replacement of proline by pipecolic acid at position B28) led to an increase in stability and a decrease in the rate of hexamer dissociation. The results of this work illustrate the pow ...
- DOI:
- 10.1002/pola.29225
- https://doi.org/10.1002/pola.29225
- Author:
- David A. Tirrell, et al. ; Peter B. Rapp; Ahmad K. Omar; Bradley R. Silverman; Zhen-Gang Wang; Show all 5 Authors
- Source:
- Journal of the American Chemical Society 2018 v.140 no.43 pp. 14185-14194
- ISSN:
- 1520-5126
- Subject:
- asymmetry; binding sites; polymers; probability; thermodynamic models
- Abstract:
- ... Networks assembled by reversible association of telechelic polymers constitute a common class of soft materials. Various mechanisms of chain migration in associative networks have been proposed; yet there remains little quantitative experimental data to discriminate among them. Proposed mechanisms for chain migration include multichain aggregate diffusion as well as single-chain mechanisms such as ...
- DOI:
- 10.1021/jacs.8b07908
- https://doi.org/10.1021/jacs.8b07908
- Author:
- David A. Tirrell, et al. ; John T. Ngo; Erin M. Schuman; Show all 3 Authors
- Source:
- Proceedings of the National Academy of Sciences of the United States of America 2013 v.110 no.13 pp. 4992-4997
- ISSN:
- 0027-8424
- Subject:
- Escherichia coli; bacteria; biopharmaceuticals; cell cycle; heterologous gene expression; mammals; mutants; protein synthesis; proteins; transfer RNA; transgenes
- Abstract:
- ... Newly synthesized cellular proteins can be tagged with a variety of metabolic labels that distinguish them from preexisting proteins and allow them to be identified and tracked. Many such labels are incorporated into proteins via the endogenous cellular machinery and can be used in numerous cell types and organisms. Though broad applicability has advantages, we aimed to develop a strategy to restr ...
- DOI:
- 10.1073/pnas.1216375110
- PubMed:
- 23479642
- PubMed Central:
- PMC3612679
- https://doi.org/10.1073/pnas.1216375110
- Author:
- David A. Tirrell, et al. ; Jacob Notbohm; Ayelet Lesman; Guruswami Ravichandran; Show all 4 Authors
- Source:
- Integrative biology 2015 v.7 no.10 pp. 1186-1195
- ISSN:
- 1757-9708
- Subject:
- deformation; fibrin; forces; image analysis; metastasis; neoplasms
- Abstract:
- ... During processes such as development and cancer metastasis, cells migrate into three-dimensional fibrous matrices. Previous studies have speculated on the mechanical forces required for migration by observing matrix fiber alignment, densification, and degradation, but these forces remain difficult to quantify. Here we present a new experimental technique to simultaneously measure full-field 3D dis ...
- DOI:
- 10.1039/c5ib00013k
- https://doi.org/10.1039/c5ib00013k
- Author:
- David A. Tirrell, et al. ; Seth A. Lieblich; Katharine Y. Fang; Jackson K. B. Cahn; Jeffrey Rawson; Jeanne LeBon; H. Teresa Ku; Show all 7 Authors
- Source:
- Journal of the American Chemical Society 2017 v.139 no.25 pp. 8384-8387
- ISSN:
- 1520-5126
- Subject:
- amyloid; crystal structure; dissociation; hydrogen bonding; hydroxylation; insulin; moieties; mutagenesis; proline
- Abstract:
- ... Daily injections of insulin provide lifesaving benefits to millions of diabetics. But currently available prandial insulins are suboptimal: The onset of action is delayed by slow dissociation of the insulin hexamer in the subcutaneous space, and insulin forms amyloid fibrils upon storage in solution. Here we show, through the use of noncanonical amino acid mutagenesis, that replacement of the prol ...
- DOI:
- 10.1021/jacs.7b00794
- PubMed:
- 28598606
- PubMed Central:
- PMC5812673
- https://doi.org/10.1021/jacs.7b00794
- Author:
- David A. Tirrell, et al. ; Fei Sun; Wen-Bin Zhang; Alborz Mahdavi; Frances H. Arnold; Show all 5 Authors
- Source:
- Proceedings of the National Academy of Sciences of the United States of America 2014 v.111 no.31 pp. 11269-11274
- ISSN:
- 0027-8424
- Subject:
- biocompatible materials; cell adhesion; embryonic stem cells; encapsulation; gelation; hydrocolloids; interstitial collagenase; leukemia inhibitory factor; ligands; mice; protein engineering; proteins
- Abstract:
- ... Protein-based hydrogels have emerged as promising alternatives to synthetic hydrogels for biomedical applications, owing to the precise control of structure and function enabled by protein engineering. Nevertheless, strategies for assembling 3D molecular networks that carry the biological information encoded in full-length proteins remain underdeveloped. Here we present a robust protein gelation s ...
- DOI:
- 10.1073/pnas.1401291111
- PubMed:
- 25049400
- PubMed Central:
- PMC4128157
- https://doi.org/10.1073/pnas.1401291111
- Author:
- David A. Tirrell, et al. ; Roland Hatzenpichler; Silvan Scheller; Patricia L. Tavormina; Brett M. Babin; Victoria J. Orphan; Show all 6 Authors
- Source:
- Environmental microbiology 2014 v.16 no.8 pp. 2568-2590
- ISSN:
- 1462-2912
- Subject:
- amino acids; biofilm; chemistry; enrichment culture; fluorescence in situ hybridization; fluorescence microscopy; fluorescent labeling; freshwater; isotope labeling; mass spectrometry; microbial physiology; microorganisms; phylogeny; protein synthesis; proteins; ribosomal RNA; sediments; stable isotopes
- Abstract:
- ... Here we describe the application of a new click chemistry method for fluorescent tracking of protein synthesis in individual microorganisms within environmental samples. This technique, termed bioorthogonal non‐canonical amino acid tagging (BONCAT), is based on the in vivo incorporation of the non‐canonical amino acid L‐azidohomoalanine (AHA), a surrogate for l‐methionine, followed by fluorescent ...
- DOI:
- 10.1111/1462-2920.12436
- PubMed:
- 24571640
- PubMed Central:
- PMC4122687
- https://doi.org/10.1111/1462-2920.12436
8. A Qrr Noncoding RNA Deploys Four Different Regulatory Mechanisms to Optimize Quorum-Sensing Dynamics
- Author:
- David A. Tirrell, et al. ; Lihui Feng; Steven T. Rutherford; Kai Papenfort; John D. Bagert; Julia C. van Kessel; Ned S. Wingreen; Bonnie L. Bassler; Show all 8 Authors
- Source:
- Cell 2015 v.160 pp. 228-240
- ISSN:
- 0092-8674
- Subject:
- bacteria; binding sites; cell communication; lifestyle; mathematical models; messenger RNA; non-coding RNA; quorum sensing; ribosomes
- Abstract:
- ... Quorum sensing is a cell-cell communication process that bacteria use to transition between individual and social lifestyles. In vibrios, homologous small RNAs called the Qrr sRNAs function at the center of quorum-sensing pathways. The Qrr sRNAs regulate multiple mRNA targets including those encoding the quorum-sensing regulatory components luxR, luxO, luxM, and aphA. We show that a representative ...
- DOI:
- 10.1016/j.cell.2014.11.051
- PubMed:
- 25579683
- PubMed Central:
- PMC4313533
- https://doi.org/10.1016/j.cell.2014.11.051
- Author:
- David A. Tirrell, et al. ; Liang Jin; Tao Feng; Hung Ping Shih; Ricardo Zerda; Angela Luo; Jasper Hsu; Alborz Mahdavi; Maike Sander; Arthur D. Riggs; Hsun Teresa Ku; Show all 11 Authors
- Source:
- Proceedings of the National Academy of Sciences of the United States of America 2013 v.110 no.10 pp. 3907-3912
- ISSN:
- 0027-8424
- Subject:
- RNA; adults; agonists; culture media; electron microscopy; hematopoiesis; hydrocolloids; immunohistochemistry; insulin-dependent diabetes mellitus; laminin; mice; pancreas; stem cells; theophylline
- Abstract:
- ... The study of hematopoietic colony-forming units using semisolid culture media has greatly advanced the knowledge of hematopoiesis. Here we report that similar methods can be used to study pancreatic colony-forming units. We have developed two pancreatic colony assays that enable quantitative and functional analyses of progenitor-like cells isolated from dissociated adult (2–4 mo old) murine pancre ...
- DOI:
- 10.1073/pnas.1301889110
- PubMed:
- 23431132
- PubMed Central:
- PMC3593860
- https://doi.org/10.1073/pnas.1301889110
- Author:
- David A. Tirrell, et al. ; Alborz Mahdavi; Janek Szychowski; John T. Ngo; Michael J. Sweredoski; Robert L. J. Graham; Sonja Hess; Olaf Schneewind; Sarkis K. Mazmanian; Show all 9 Authors
- Source:
- Proceedings of the National Academy of Sciences of the United States of America 2014 v.111 no.1 pp. 433-438
- ISSN:
- 0027-8424
- Subject:
- Yersinia enterocolitica; bacteria; bacterial proteins; drug therapy; humans; methionine; mutants; pathogens; secretion; translation (genetics); type III secretion system; virulence
- Abstract:
- ... Pathogenic microbes have evolved complex secretion systems to deliver virulence factors into host cells. Identification of these factors is critical for understanding the infection process. We report a powerful and versatile approach to the selective labeling and identification of secreted pathogen proteins. Selective labeling of microbial proteins is accomplished via translational incorporation o ...
- DOI:
- 10.1073/pnas.1301740111
- PubMed:
- 24347637
- PubMed Central:
- PMC3890788
- https://doi.org/10.1073/pnas.1301740111
- Author:
- David A. Tirrell, et al. ; Kai P. Yuet; Meenakshi K. Doma; John T. Ngo; Michael J. Sweredoski; Robert L. J. Graham; Annie Moradian; Sonja Hess; Erin M. Schuman; Paul W. Sternberg; Show all 10 Authors
- Source:
- Proceedings of the National Academy of Sciences of the United States of America 2015 v.112 no.9 pp. 2705-2710
- ISSN:
- 0027-8424
- Subject:
- Caenorhabditis elegans; animals; integument; intestinal mucosa; isotope labeling; mass spectrometry; muscles; neurons; protein synthesis; proteins; proteomics
- Abstract:
- ... Proteomic analysis of rare cells in heterogeneous environments presents difficult challenges. Systematic methods are needed to enrich, identify, and quantify proteins expressed in specific cells in complex biological systems including multicellular plants and animals. Here, we have engineered a Caenorhabditis elegans phenylalanyl-tRNA synthetase capable of tagging proteins with the reactive noncan ...
- DOI:
- 10.1073/pnas.1421567112
- PubMed:
- 25691744
- PubMed Central:
- PMC4352802
- https://doi.org/10.1073/pnas.1421567112