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727 results on '"Kiessling, Laura L."'

1. Identification of d-arabinan-degrading enzymes in mycobacteria

Author

Al-Jourani, Omar, Benedict, Samuel T., Ross, Jennifer, Layton, Abigail J., van der Peet, Phillip, Marando, Victoria M., Bailey, Nicholas P., Heunis, Tiaan, Manion, Joseph, Mensitieri, Francesca, Franklin, Aaron, Abellon-Ruiz, Javier, Oram, Sophia L., Parsons, Lauren, Cartmell, Alan, Wright, Gareth S. A., Baslé, Arnaud, Trost, Matthias, Henrissat, Bernard, Munoz-Munoz, Jose, Hirt, Robert P., Kiessling, Laura L., Lovering, Andrew L., Williams, Spencer J., Lowe, Elisabeth C., and Moynihan, Patrick J.

Published
2023
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3. Human intelectin-1 (ITLN1) genetic variation and intestinal expression.

Author

Nonnecke, Eric B, Castillo, Patricia A, Dugan, Amanda E, Almalki, Faisal, Underwood, Mark A, De La Motte, Carol A, Yuan, Weirong, Lu, Wuyuan, Shen, Bo, Johansson, Malin EV, Kiessling, Laura L, Hollox, Edward J, Lönnerdal, Bo, and Bevins, Charles L

Abstract

Intelectins are ancient carbohydrate binding proteins, spanning chordate evolution and implicated in multiple human diseases. Previous GWAS have linked SNPs in ITLN1 (also known as omentin) with susceptibility to Crohn's disease (CD); however, analysis of possible functional significance of SNPs at this locus is lacking. Using the Ensembl database, pairwise linkage disequilibrium (LD) analyses indicated that several disease-associated SNPs at the ITLN1 locus, including SNPs in CD244 and Ly9, were in LD. The alleles comprising the risk haplotype are the major alleles in European (67%), but minor alleles in African superpopulations. Neither ITLN1 mRNA nor protein abundance in intestinal tissue, which we confirm as goblet-cell derived, was altered in the CD samples overall nor when samples were analyzed according to genotype. Moreover, the missense variant V109D does not influence ITLN1 glycan binding to the glycan β-D-galactofuranose or protein-protein oligomerization. Taken together, our data are an important step in defining the role(s) of the CD-risk haplotype by determining that risk is unlikely to be due to changes in ITLN1 carbohydrate recognition, protein oligomerization, or expression levels in intestinal mucosa. Our findings suggest that the relationship between the genomic data and disease arises from changes in CD244 or Ly9 biology, differences in ITLN1 expression in other tissues, or an alteration in ITLN1 interaction with other proteins.

Published
2021

4. Stereochemical Control Yields Mucin Mimetic Polymers

Author

Kruger, Austin G, Brucks, Spencer D, Yan, Tao, Cárcarmo-Oyarce, Gerardo, Wei, Yuan, Wen, Deborah H, Carvalho, Dayanne R, Hore, Michael JA, Ribbeck, Katharina, Schrock, Richard R, and Kiessling, Laura L

Subjects
Lung, Rare Diseases, Vaccine Related, Bioengineering, Cystic Fibrosis, Good Health and Well Being, Chemical Sciences
Abstract

All animals except sponges produce mucus. Across the animal kingdom, this hydrogel mediates surface wetting, viscosity, and protection against microbes. The primary components of mucus hydrogels are mucins-high molecular weight O-glycoproteins that adopt extended linear structures. Glycosylation is integral to mucin function, but other characteristics that give rise to their advantageous biological activities are unknown. We postulated that the extended conformation of mucins is critical for their ability to block microbial virulence phenotypes. To test this hypothesis, we developed synthetic mucin mimics that recapitulate the dense display of glycans and morphology of mucin. We varied the catalyst in a ring-opening metathesis polymerization (ROMP) to generate substituted norbornene-derived glycopolymers containing either cis- or trans-alkenes. Conformational analysis of the polymers based on allylic strain suggested that cis- rather than trans-poly(norbornene) glycopolymers would adopt linear structures that mimic mucins. High-resolution atomic force micrographs of our polymers and natively purified Muc2, Muc5AC, and Muc5B mucins revealed that cis-polymers adopt extended, mucin-like structures. The cis-polymers retained this structure in solution and were more water-soluble than their trans-analogs. Consistent with mucin's linear morphology, cis-glycopolymers were more potent binders of a bacterial virulence factor, cholera toxin. Our findings highlight the importance of the polymer backbone in mucin surrogate design and underscore the significance of the extended mucin backbone for inhibiting virulence.

Published
2021

5. Voices in methods development.

Author

Anikeeva, Polina, Boyden, Edward, Brangwynne, Clifford, Cissé, Ibrahim I, Fiehn, Oliver, Fromme, Petra, Gingras, Anne-Claude, Greene, Casey S, Heard, Edith, Hell, Stefan W, Hillman, Elizabeth, Jensen, Grant Jay, Karchin, Rachel, Kiessling, Laura L, Kleinstiver, Benjamin P, Knight, Rob, Kukura, Philipp, Lancaster, Madeline A, Loman, Nicholas, Looger, Loren, Lundberg, Emma, Luo, Qingming, Miyawaki, Atsushi, Myers, Eugene W, Nolan, Garry P, Picotti, Paola, Reik, Wolf, Sauer, Markus, Shalek, Alex K, Shendure, Jay, Slavov, Nikolai, Tanay, Amos, Troyanskaya, Olga, van Valen, David, Wang, Hong-Wei, Yi, Chengqi, Yin, Peng, Zernicka-Goetz, Magdalena, and Zhuang, Xiaowei

Subjects
Biological Sciences, Technology, Medical and Health Sciences, Developmental Biology
Abstract

To mark the 15th anniversary of Nature Methods, we asked scientists from across diverse fields of basic biology research for their views on the most exciting and essential methodological challenges that their communities are poised to tackle in the near future.

Published
2019

6. Massively parallel combination screen reveals small molecule sensitization of antibiotic-resistant Gram-negative ESKAPE pathogens

Author

Tse, Megan W., primary, Zhu, Meilin, additional, Peters, Benjamin, additional, Hamami, Efrat, additional, Chen, Julie, additional, Davis, Kathleen P., additional, Nitz, Samuel, additional, Weller, Juliane, additional, Warrier, Thulasi, additional, Hunt, Diana K., additional, Morales, Yoelkys, additional, Kawate, Tomohiko, additional, Gaulin, Jeffrey L., additional, Come, Jon H., additional, Hernandez-Bird, Juan, additional, Huo, Wenwen, additional, Neisewander, Isabelle, additional, Kiessling, Laura L., additional, Hung, Deborah T., additional, Mecsas, Joan, additional, Aldridge, Bree B., additional, Isberg, Ralph R., additional, and Blainey, Paul C., additional

Published
2024
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9. A proteome-wide atlas of lysine-reactive chemistry

Author

Abbasov, Mikail E., Kavanagh, Madeline E., Ichu, Taka-Aki, Lazear, Michael R., Tao, Yongfeng, Crowley, Vincent M., am Ende, Christopher W., Hacker, Stephan M., Ho, Jordan, Dix, Melissa M., Suciu, Radu, Hayward, Matthew M., Kiessling, Laura L., and Cravatt, Benjamin F.

Published
2021
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10. Polymers at the Interface with Biology

Author

Deming, Timothy J, Klok, Harm-Anton, Armes, Steven P, Becker, Matthew L, Champion, Julie A, Chen, Eugene Y-X, Heilshorn, Sarah C, van Hest, Jan CM, Irvine, Darrell J, Johnson, Jeremiah A, Kiessling, Laura L, Maynard, Heather D, de la Cruz, Monica Olvera, Sullivan, Millicent O, Tirrell, Matthew V, Anseth, Kristi S, Lecommandoux, Sebastien, Percec, Simona, Zhong, Zhiyuan, and Albertsson, Ann-Christine

Subjects
Biocompatible Materials, Bioengineering, Nanoparticles, Chemical Sciences, Biological Sciences, Engineering, Polymers
Published
2018

11. Spotlight: A Conversation with Laura Kiessling and Jennifer Doudna

Author

Kiessling, Laura L and Doudna, Jennifer A

Subjects
Biology, CRISPR-Associated Proteins, CRISPR-Cas Systems, Gene Editing, History, 20th Century, History, 21st Century, RNA, Catalytic, RNA, Guide, Kinetoplastida, RNA, Guide, Chemical Sciences, Biological Sciences, Organic Chemistry
Abstract

ACS Chemical Biology recorded a special podcast, in which Editor-in-Chief Laura Kiessling (Massachusetts Institute of Technology) interviews CRISPR investigator and former Associate Editor Jennifer Doudna (University of California, Berkeley). Listen to the podcast here . A transcript of the interview, which has been lightly edited, is published here as part of our Special Issue on the Chemical Biology of CRISPR.

Published
2018

12. How many human proteoforms are there?

Author

Aebersold, Ruedi, Agar, Jeffrey N, Amster, I Jonathan, Baker, Mark S, Bertozzi, Carolyn R, Boja, Emily S, Costello, Catherine E, Cravatt, Benjamin F, Fenselau, Catherine, Garcia, Benjamin A, Ge, Ying, Gunawardena, Jeremy, Hendrickson, Ronald C, Hergenrother, Paul J, Huber, Christian G, Ivanov, Alexander R, Jensen, Ole N, Jewett, Michael C, Kelleher, Neil L, Kiessling, Laura L, Krogan, Nevan J, Larsen, Martin R, Loo, Joseph A, Ogorzalek Loo, Rachel R, Lundberg, Emma, MacCoss, Michael J, Mallick, Parag, Mootha, Vamsi K, Mrksich, Milan, Muir, Tom W, Patrie, Steven M, Pesavento, James J, Pitteri, Sharon J, Rodriguez, Henry, Saghatelian, Alan, Sandoval, Wendy, Schlüter, Hartmut, Sechi, Salvatore, Slavoff, Sarah A, Smith, Lloyd M, Snyder, Michael P, Thomas, Paul M, Uhlén, Mathias, Van Eyk, Jennifer E, Vidal, Marc, Walt, David R, White, Forest M, Williams, Evan R, Wohlschlager, Therese, Wysocki, Vicki H, Yates, Nathan A, Young, Nicolas L, and Zhang, Bing

Subjects
Humans, Proteins, Protein Isoforms, Proteome, Ubiquitin, Proteomics, Protein Biosynthesis, Protein Processing, Post-Translational, Phenotype, Genome, Human, Databases, Protein, Mass Spectrometry, Genetics, Underpinning research, 1.1 Normal biological development and functioning, Generic health relevance, Medicinal and Biomolecular Chemistry, Biochemistry and Cell Biology, Biochemistry & Molecular Biology
Abstract

Despite decades of accumulated knowledge about proteins and their post-translational modifications (PTMs), numerous questions remain regarding their molecular composition and biological function. One of the most fundamental queries is the extent to which the combinations of DNA-, RNA- and PTM-level variations explode the complexity of the human proteome. Here, we outline what we know from current databases and measurement strategies including mass spectrometry-based proteomics. In doing so, we examine prevailing notions about the number of modifications displayed on human proteins and how they combine to generate the protein diversity underlying health and disease. We frame central issues regarding determination of protein-level variation and PTMs, including some paradoxes present in the field today. We use this framework to assess existing data and to ask the question, "How many distinct primary structures of proteins (proteoforms) are created from the 20,300 human genes?" We also explore prospects for improving measurements to better regularize protein-level biology and efficiently associate PTMs to function and phenotype.

Published
2018

15. Glycan-costumed virus-like particles promote type 1 anti-tumor immunity

Author

Lensch, Valerie, primary, Gabba, Adele, additional, Hincapie, Robert, additional, Bhagchandani, Sachin H., additional, Basak, Ankit, additional, Alam, Mohammad Murshid, additional, Irvine, Darrell J., additional, Shalek, Alex K., additional, Johnson, Jeremiah A., additional, Finn, M. G., additional, and Kiessling, Laura L., additional

Published
2024
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17. Nanoscience and Nanotechnology Cross Borders.

Author

Khademhosseini, Ali, Chan, Warren WC, Chhowalla, Manish, Glotzer, Sharon C, Gogotsi, Yury, Hafner, Jason H, Hammond, Paula T, Hersam, Mark C, Javey, Ali, Kagan, Cherie R, Kotov, Nicholas A, Lee, Shuit-Tong, Li, Yan, Möhwald, Helmuth, Mulvaney, Paul A, Nel, Andre E, Parak, Wolfgang J, Penner, Reginald M, Rogach, Andrey L, Schaak, Raymond E, Stevens, Molly M, Wee, Andrew TS, Brinker, Jeffrey, Chen, Xiaoyuan, Chi, Lifeng, Crommie, Michael, Dekker, Cees, Farokhzad, Omid, Gerber, Christoph, Ginger, David S, Irvine, Darrell J, Kiessling, Laura L, Kostarelos, Kostas, Landes, Christy, Lee, Takhee, Leggett, Graham J, Liang, Xing-Jie, Liz-Marzán, Luis, Millstone, Jill, Odom, Teri W, Ozcan, Aydogan, Prato, Maurizio, Rao, CNR, Sailor, Michael J, Weiss, Emily, and Weiss, Paul S

Subjects
Nanoscience & Nanotechnology
Published
2017

20. Virtual Screening for UDP-Galactopyranose Mutase Ligands Identifies a New Class of Antimycobacterial Agents

Author

Kincaid, Virginia A, London, Nir, Wangkanont, Kittikhun, Wesener, Darryl A, Marcus, Sarah A, Héroux, Annie, Nedyalkova, Lyudmila, Talaat, Adel M, Forest, Katrina T, Shoichet, Brian K, and Kiessling, Laura L

Subjects
Biochemistry and Cell Biology, Medicinal and Biomolecular Chemistry, Chemical Sciences, Biological Sciences, Rare Diseases, 5.1 Pharmaceuticals, Development of treatments and therapeutic interventions, Good Health and Well Being, Anti-Bacterial Agents, Crystallography, X-Ray, Drug Evaluation, Preclinical, Intramolecular Transferases, Ligands, Models, Biological, Molecular Docking Simulation, Molecular Structure, Organic Chemistry, Biological sciences, Chemical sciences
Abstract

Galactofuranose (Galf) is present in glycans critical for the virulence and viability of several pathogenic microbes, including Mycobacterium tuberculosis, yet the monosaccharide is absent from mammalian glycans. Uridine 5'-diphosphate-galactopyranose mutase (UGM) catalyzes the formation of UDP-Galf, which is required to produce Galf-containing glycoconjugates. Inhibitors of UGM have therefore been sought, both as antimicrobial leads and as tools to delineate the roles of Galf in cells. Obtaining cell permeable UGM probes by either design or high throughput screens has been difficult, as has elucidating how UGM binds small molecule, noncarbohydrate inhibitors. To address these issues, we employed structure-based virtual screening to uncover new inhibitor chemotypes, including a triazolothiadiazine series. These compounds are among the most potent antimycobacterial UGM inhibitors described. They also facilitated determination of a UGM-small molecule inhibitor structure, which can guide optimization. A comparison of results from the computational screen and a high-throughput fluorescence polarization (FP) screen indicated that the scaffold hits from the former had been evaluated in the FP screen but missed. By focusing on promising compounds, the virtual screen rescued false negatives, providing a blueprint for generating new UGM probes and therapeutic leads.

Published
2015

23. Lectin-Seq: A method to profile lectin-microbe interactions in native communities

Author

McPherson, Robert L., primary, Isabella, Christine R., additional, Walker, Rebecca L., additional, Sergio, Dallis, additional, Bae, Sunhee, additional, Gaca, Tony, additional, Raman, Smrithi, additional, Nguyen, Le Thanh Tu, additional, Wesener, Darryl A., additional, Halim, Melanie, additional, Wuo, Michael G., additional, Dugan, Amanda, additional, Kerby, Robert, additional, Ghosh, Soumi, additional, Rey, Federico E., additional, Dhennezel, Catherine, additional, Pishchany, Gleb, additional, Lensch, Valerie, additional, Vlamakis, Hera, additional, Alm, Eric J., additional, Xavier, Ramnik J., additional, and Kiessling, Laura L., additional

Published
2023
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26. Human oral lectin ZG16B acts as a cell wall polysaccharide probe to decode host–microbe interactions with oral commensals

Author

Ghosh, Soumi, primary, Ahearn, Christian P., additional, Isabella, Christine R., additional, Marando, Victoria M., additional, Dodge, Gregory J., additional, Bartlett, Helen, additional, McPherson, Robert L., additional, Dugan, Amanda E., additional, Jain, Shikha, additional, Neznanova, Lubov, additional, Tettelin, Hervé, additional, Putnik, Rachel, additional, Grimes, Catherine L., additional, Ruhl, Stefan, additional, Kiessling, Laura L., additional, and Imperiali, Barbara, additional

Published
2023
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27. Lectin Fingerprinting Distinguishes Antibody Neutralization in SARS-CoV-2

Author

Wuo, Michael G., primary, Dugan, Amanda E., additional, Halim, Melanie, additional, Hauser, Blake M., additional, Feldman, Jared, additional, Caradonna, Timothy M., additional, Zhang, Shuting, additional, Pepi, Lauren E., additional, Atyeo, Caroline, additional, Fischinger, Stephanie, additional, Alter, Galit, additional, Garcia-Beltran, Wilfredo F., additional, Azadi, Parastoo, additional, Hung, Deb, additional, Schmidt, Aaron G., additional, and Kiessling, Laura L., additional

Published
2023
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32. Lectin-Seq: a method to profile lectin-microbe interactions in native communities

Author

McPherson, Robert L., primary, Isabella, Christine R., additional, Walker, Rebecca L., additional, Sergio, Dallis, additional, Bae, Sunhee, additional, Gaca, Tony, additional, Raman, Smrithi, additional, Nguyen, Le Thanh Tu, additional, Wesener, Darryl A., additional, Halim, Melanie, additional, Wuo, Michael G., additional, Dugan, Amanda, additional, Kerby, Robert, additional, Ghosh, Soumi, additional, Rey, Federico E., additional, Dhennezel, Catherine, additional, Pishchany, Gleb, additional, Vlamakis, Hera, additional, Alm, Eric J., additional, Xavier, Ramnik J., additional, and Kiessling, Laura L., additional

Published
2022
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35. Virtual screening for small-molecule pathway regulators by image-profile matching

Author

Rohban, Mohammad H., primary, Fuller, Ashley M., additional, Tan, Ceryl, additional, Goldstein, Jonathan T., additional, Syangtan, Deepsing, additional, Gutnick, Amos, additional, DeVine, Ann, additional, Nijsure, Madhura P., additional, Rigby, Megan, additional, Sacher, Joshua R., additional, Corsello, Steven M., additional, Peppler, Grace B., additional, Bogaczynska, Marta, additional, Boghossian, Andrew, additional, Ciotti, Gabrielle E., additional, Hands, Allison T., additional, Mekareeya, Aroonroj, additional, Doan, Minh, additional, Gale, Jennifer P., additional, Derynck, Rik, additional, Turbyville, Thomas, additional, Boerckel, Joel D., additional, Singh, Shantanu, additional, Kiessling, Laura L., additional, Schwarz, Thomas L., additional, Varelas, Xaralabos, additional, Wagner, Florence F., additional, Kafri, Ran, additional, Eisinger-Mathason, T.S. Karin, additional, and Carpenter, Anne E., additional

Published
2022
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36. Rapid Single-Shot Synthesis of the 217 Amino Acid-Long N-Terminal Domain of Pyocin S2

Author

Saebi, Azin, Brown, Joseph S, Marando, Victoria M, Hartrampf, Nina, Chumbler, Nicole M, Hanna, Stephanie, Poskus, Mackenzie, Loas, Andrei, Kiessling, Laura L, Hung, Deborah T, Pentelute, Bradley L, and University of Zurich

Subjects
10120 Department of Chemistry, 540 Chemistry
Abstract

The impermeable outer membrane ofPseudomonas aeruginosais bypassed by antibacterial proteins known as S-type pyocins. Because of their properties, pyocins are investigated as a potential new class of antimicrobials againstPseudomonasinfections. Their production and modification, however, remains challenging. To address this limitation, we employed automated fast-flow peptide synthesis (AFPS) for the rapid production of a pyocin S2 import domain. The N-terminal domain sequence (PyS2NTD) was synthesized in under 10 hours and purified to yield milligrams quantities of the desired product. To our knowledge, the 217 amino acid sequence of PyS2NTDis among the longest peptides produced from a “single-shot” synthesis, i.e., made in a single stepwise route without the use of ligation techniques. Biophysical characterization of the PyS2NTDwith circular dichroism was consistent with the literature reports. Fluorescently labeled PyS2NTDbinds toP. aeruginosaexpressing the cognate ferripyoverdine receptor (FpvA) and is taken up into the periplasm. This selective uptake was validated with confocal and super resolution microscopy, flow cytometry, and fluorescence recovery after photobleaching (FRAP). These modified, synthetic S-type pyocins domains can be used to probe import mechanisms ofP. aeruginosaand leveraged to develop selective antimicrobial agents that bypass the outer membrane.

Published
2022

41. Mining the human gut microbiome identifies mycobacterial d-arabinan degrading enzymes

Author

Al-Jourani, Omar, primary, Benedict, Samuel, additional, Ross, Jennifer, additional, Layton, Abigail, additional, van der Peet, Phillip, additional, Marando, Victoria M., additional, Bailey, Nicholas P., additional, Heunis, Tiaan, additional, Manion, Joseph, additional, Mensitieri, Francesca, additional, Franklin, Aaron, additional, Abellon-Ruiz, Javier, additional, Oram, Sophia L., additional, Parsons, Lauren, additional, Cartmell, Alan, additional, Wright, Gareth S. A., additional, Baslé, Arnaud, additional, Trost, Matthias, additional, Henrissat, Bernard, additional, Munoz-Munoz, Jose, additional, Hirt, Robert P., additional, Kiessling, Laura L., additional, Lovering, Andrew, additional, Williams, Spencer J., additional, Lowe, Elisabeth C., additional, and Moynihan, Patrick J., additional

Published
2022
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46. Antibiotic action revealed by real-time imaging of the mycobacterial membrane

Author

Wuo, Michael G., primary, Dulberger, Charles L., additional, Brown, Robert A., additional, Sturm, Alexander, additional, Ultee, Eveline, additional, Bloom-Ackermann, Zohar, additional, Choi, Catherine, additional, Garner, Ethan C., additional, Briegel, Ariane, additional, Hung, Deborah T., additional, Rubin, Eric J., additional, and Kiessling, Laura L., additional

Published
2022
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48. Advancing Chemical Microbiology

Author

Kiessling, Laura L. and Carlson, Erin E.

Subjects
Biological Products, 2019-20 coronavirus outbreak, Bacteria, Coronavirus disease 2019 (COVID-19), Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Optical Imaging, Mutagenesis (molecular biology technique), Drug Resistance, Microbial, General Medicine, Drug resistance, Biology, biology.organism_classification, Biochemistry, Microbiology, Optical imaging, Anti-Infective Agents, Mutagenesis, Viruses, Humans, Metabolomics, Molecular Medicine, Peptides, Fluorescent Dyes
Published
2020

49. Bioactive Polymers

Author

Kiessling, Laura L., Strong, Laura E., Brown, John M., editor, Dixneuf, Pierre, editor, Hegedus, Louis S., editor, Hofmann, Peter, editor, Knochel, Paul, editor, van Koten, Gerard, editor, Marks, Tobin J., editor, Murai, Shinji, editor, Reetz, Manfred, editor, and Fürstner, Alois, editor

Published
1998
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