Glycobiology vol. 24 no. 3 pp. 218–219, 2014 doi:10.1093/glycob/cwu007
Glyco-Forum section Latest advances in glycobiology highlighted and old challenges revisited at the 2013 Annual Conference of the Society for Glycobiology
University of Oklahoma Health Sciences Center
The 2013 Conference celebrated our 40th anniversary as a society and met at a new venue—the historic Vinoy hotel in the downtown St. Petersburg (Florida) hotel and restaurant district on the Tampa Bay waterfront. The goals of this year’s meeting were to highlight major advances in glycobiology and to help break down technical barriers presented by the complexity of epigenetic regulatory processes like glycosylation. The diversity of subjects covered by the 32 long talks and 27 short talks invited from abstracts was truly impressive and identified many frontiers to explore for the foreseeable future. The opening session exemplified the power of technology for advancing glycobiology—mass spec and Next Gen sequencing are two of the most important technologies fuelling our field. One of the greats of biological mass spectrometry—Al Burlingame—was presented the MCP Lectureship Award by Jerry Hart. Al then told the meeting how electron transfer mass spectrometry has transformed site analysis in the O-GlcNAc field—remarkably his team has mapped over 1600 O-GlcNAc and 16,000 phosphorylation sites. It was great to have plant glycobiology at the forefront of the meeting—Markus Pauly highlighted the beauty and complexity of plant cell walls and told us how Next Gen sequencing is accelerating the identification of glycosyltransferases involved in their biosynthesis with implications for bioenergy and industrial biotechnology. Stuart Haslam returned to the power of mass spectrometry to end the session. He described the application of state-of-the-art glycomic and glycoproteomic methodologies to research in developmental biology and congenital disorders of glycosylation. Model organisms were well-represented, where pioneering studies in O-glycosylation continue to reveal new secrets about developmental regulation. Hamed Jafar-Nejad illustrated how O-Glc functions extend beyond Notch, Bob Haltiwanger revealed chaperone-like functions for POFUT-2, another talk uncovered roles of mucin-type O-glycans in polarized secretion, and Takako Yoshida-Moriguchi revealed the identity of a mannose kinase and two more glycosyltransferases whose functions are compromised in muscular dystrophies. For her work she received the BBA General Subjects Young Investigator Award.
The topic of biosynthesis kicked off with the demystification by Jochen Zimmer of how cellulose is transferred from its cytoplasmic origin of synthesis to the cell surface. Mark Lehrman focused our attention on unexpected metabolic factors that regulated N-glycosylation. Kelley Moremen highlighted the new glycosyltransferase resource and used his group’s success at crystallizing ST6Gal-I as an example of its value to the community. Chemical glycobiology is a major growth area and Geert-Jan Boons presented a remarkable array of N-glycans that could be achieved by chemoenzymatic syntheses. The utility of glycan microarrays was demonstrated by the surprising diversity of milk glycan recognition patterns by rotavirus isolates. Jennifer Kohler used a novel photo-crosslinkable sugar precursor to identify a novel cholera toxin receptor glycoprotein which could redefine disease mechanism. The session on Inhibitors impressively demonstrated that small molecules with nanomolar Ki values can now be designed to specifically inhibit protein-carbohydrate recognition (Beat Ernst and Thomas Peters). The design component includes tailoring the bioavailability of the compounds, and some have made it to human clinical trials. Bisubstrate conjugates show promise in inhibiting OGT as demonstrated by David Vocadlo, who also emphasized how structure-based inhibitors of O-GlcNAc removal may have relevance for Alzheimer therapies. Other talks emphasized novel associations of O-GlcNAc with mitochondrial electron transport, arginine methyltransferases, and X-linked intellectual disabilities. The talks from glycobiologists and infectious disease experts on glyco-related aspects of bacterial pathogenesis (Mario Feldman), African trypanosomiasis (Jay Bangs), fungal chitin
© The Author 2014. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: [email protected]
218
Downloaded from http://glycob.oxfordjournals.org/ at University of Michigan on June 20, 2015
Christopher M West
Glyco-Forum section
whether to fine-tune immune responses or alter host response to pathogens or to correct in-born errors. A unique highlight of the conference was an appeal from a family of a CDG child—with a deficiency in cytoplasmic N-glycanase—to keep up the good work that will someday find a cure. Tadashi Suzuki presented a biochemical accounting of free oligosaccharides connected with this deficiency, and Hud Freeze explained the power of exome sequencing for its diagnostic and research discovery value for this and other CDGs. Another event was the roundtable discussion led by Pam Marino from NIGMS, Karl Krueger from NCI, and Hud Freeze as SfG’s FASEB representative, where programmatic interests and opportunities at NIH and funding issues were discussed. The Society’s Karl Meyer Lectureship Award was delivered by Marcus Aebi, who gave a terrific overview of the evolution, mechanism and functions of protein N-glycosylation and the seminal contributions of his group to this universally important pathway. The Rosalind Kornfeld Lifetime Achievement Award honored Carlos Hirschberg, who delivered a characteristically disciplined account of the biochemical and physiological roles of the sugar nucleotide transporters. The traditional dinner banquet featured a local classic rock band with special performances by Jamey Marth and Osman Sheikh- new contact opportunities presented themselves on the dance floor too. Space does not permit summarizing the over 265 posters, 27 of which were selected for short-talk presentations. Suffice it to say that these, together with the 15 industry sponsorship booths, constituted a second nexus at the conference that nicely complemented the speaker program. Together with the three one-day Satellite Meetings (SfG-sponsored Junior Scientist Pre-Conference, CFG-sponsored Development and Application of Transformative Technologies in Glycobiology, and Industry-sponsored Glycoprotein Technologies) held before the conference, there was something sweet for every glycoscientist to taste. Next year’s conference—Integrating Glycoscience from Biology and Chemistry to Medicine—will be held jointly with the Japanese Society for Carbohydrate Research on November 16–19 at the Hilton Hawaiian Village Waikiki Beach Resort in Honolulu, Hawaii. Scheduled 10 years following the highly successful 2004 joint conference at the same venue, the 2014 version will be organized by Naoyuki Taniguchi (2014 SfG President) and Yukishige Ito (2014 JSCR President).
219
Downloaded from http://glycob.oxfordjournals.org/ at University of Michigan on June 20, 2015
regulation of the immune response (Neil Gow), and the hygiene hypothesis (Brian Cobb), emphasized that we have only seen the tip of the glycobiology iceberg in parasites and regulation of host immune responses. Having non-traditional Glycobiology speakers integrate glyco-thinking into their work will doubtless catalyze new collaborative opportunities in the future. In the International Glycoconjugate Organization-sponsored guest session on Cancer Glycobiology, heparan sulfate was assigned fundamental roles in prostate and colon cancer stem cell biology by Lianchun Wang and Minoru Fukuda. Tn-antigen and STn expression are associated with numerous tumors and Kazuaki Ohtsubo related these antigens to hypoxia, TGFbeta signaling, and EMT. John Yu emphasized the importance of glycosphingolipids and protein glycoantigens as stem cell markers that are ripe for exploitation to monitor and test as vaccines for various cancers. The vascular system is yet another organ system rich in glyco-specializations. Alan Rapraeger demonstrated the importance of receptor tyrosine kinase complexes with syndecan in angiogenesis. Jamey Marth discussed new roles for hepatic glycan receptors in management of bacterial sepsis. In a counter to dogma, Joe Lau documented how a sialyltransferase produced in the liver is transported to the bone marrow to promote hematopoiesis using sugar nucleotides secreted from platelets. Lijun Xia described new examples of the importance of O-glycosylation in podoplanin regulation of platelet activity in lymphangiogenesis and vascular integrity. In research with more direct translational implications, Karin Hoffmeister documented the importance of glycan processing enzymes in platelet birth and aging, and Paul DeAngelis rolled out a heparosan substitute for PEGylation to improve protein drug delivery. In the session on Human Disease, take-home messages included 1) a wide variety of systems, from cells to zebrafish to mice to humans, are being utilized to understand different human disorders (Stuart Kornfeld); 2) we are increasingly seeing exquisite biologic complexity related to glycans, whether it is different phenotypes of various CDGs (Hud Freeze) or the discrete roles of the different mucus layers in the colon in regulating access of microbes to host epithelia (Gunnar Hansson) or the discrimination of different cellular glycans by lectins on immune cells (Yvette van Kooyk); and 3) modification of cellular glycans will be a major goal of future therapies,
Glyco-Forum section Latest advances in glycobiology highlighted and old challenges revisited at the 2013 Annual Conference of the Society for Glycobiology
University of Oklahoma Health Sciences Center
The 2013 Conference celebrated our 40th anniversary as a society and met at a new venue—the historic Vinoy hotel in the downtown St. Petersburg (Florida) hotel and restaurant district on the Tampa Bay waterfront. The goals of this year’s meeting were to highlight major advances in glycobiology and to help break down technical barriers presented by the complexity of epigenetic regulatory processes like glycosylation. The diversity of subjects covered by the 32 long talks and 27 short talks invited from abstracts was truly impressive and identified many frontiers to explore for the foreseeable future. The opening session exemplified the power of technology for advancing glycobiology—mass spec and Next Gen sequencing are two of the most important technologies fuelling our field. One of the greats of biological mass spectrometry—Al Burlingame—was presented the MCP Lectureship Award by Jerry Hart. Al then told the meeting how electron transfer mass spectrometry has transformed site analysis in the O-GlcNAc field—remarkably his team has mapped over 1600 O-GlcNAc and 16,000 phosphorylation sites. It was great to have plant glycobiology at the forefront of the meeting—Markus Pauly highlighted the beauty and complexity of plant cell walls and told us how Next Gen sequencing is accelerating the identification of glycosyltransferases involved in their biosynthesis with implications for bioenergy and industrial biotechnology. Stuart Haslam returned to the power of mass spectrometry to end the session. He described the application of state-of-the-art glycomic and glycoproteomic methodologies to research in developmental biology and congenital disorders of glycosylation. Model organisms were well-represented, where pioneering studies in O-glycosylation continue to reveal new secrets about developmental regulation. Hamed Jafar-Nejad illustrated how O-Glc functions extend beyond Notch, Bob Haltiwanger revealed chaperone-like functions for POFUT-2, another talk uncovered roles of mucin-type O-glycans in polarized secretion, and Takako Yoshida-Moriguchi revealed the identity of a mannose kinase and two more glycosyltransferases whose functions are compromised in muscular dystrophies. For her work she received the BBA General Subjects Young Investigator Award.
The topic of biosynthesis kicked off with the demystification by Jochen Zimmer of how cellulose is transferred from its cytoplasmic origin of synthesis to the cell surface. Mark Lehrman focused our attention on unexpected metabolic factors that regulated N-glycosylation. Kelley Moremen highlighted the new glycosyltransferase resource and used his group’s success at crystallizing ST6Gal-I as an example of its value to the community. Chemical glycobiology is a major growth area and Geert-Jan Boons presented a remarkable array of N-glycans that could be achieved by chemoenzymatic syntheses. The utility of glycan microarrays was demonstrated by the surprising diversity of milk glycan recognition patterns by rotavirus isolates. Jennifer Kohler used a novel photo-crosslinkable sugar precursor to identify a novel cholera toxin receptor glycoprotein which could redefine disease mechanism. The session on Inhibitors impressively demonstrated that small molecules with nanomolar Ki values can now be designed to specifically inhibit protein-carbohydrate recognition (Beat Ernst and Thomas Peters). The design component includes tailoring the bioavailability of the compounds, and some have made it to human clinical trials. Bisubstrate conjugates show promise in inhibiting OGT as demonstrated by David Vocadlo, who also emphasized how structure-based inhibitors of O-GlcNAc removal may have relevance for Alzheimer therapies. Other talks emphasized novel associations of O-GlcNAc with mitochondrial electron transport, arginine methyltransferases, and X-linked intellectual disabilities. The talks from glycobiologists and infectious disease experts on glyco-related aspects of bacterial pathogenesis (Mario Feldman), African trypanosomiasis (Jay Bangs), fungal chitin
© The Author 2014. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: [email protected]
218
Downloaded from http://glycob.oxfordjournals.org/ at University of Michigan on June 20, 2015
Christopher M West
Glyco-Forum section
whether to fine-tune immune responses or alter host response to pathogens or to correct in-born errors. A unique highlight of the conference was an appeal from a family of a CDG child—with a deficiency in cytoplasmic N-glycanase—to keep up the good work that will someday find a cure. Tadashi Suzuki presented a biochemical accounting of free oligosaccharides connected with this deficiency, and Hud Freeze explained the power of exome sequencing for its diagnostic and research discovery value for this and other CDGs. Another event was the roundtable discussion led by Pam Marino from NIGMS, Karl Krueger from NCI, and Hud Freeze as SfG’s FASEB representative, where programmatic interests and opportunities at NIH and funding issues were discussed. The Society’s Karl Meyer Lectureship Award was delivered by Marcus Aebi, who gave a terrific overview of the evolution, mechanism and functions of protein N-glycosylation and the seminal contributions of his group to this universally important pathway. The Rosalind Kornfeld Lifetime Achievement Award honored Carlos Hirschberg, who delivered a characteristically disciplined account of the biochemical and physiological roles of the sugar nucleotide transporters. The traditional dinner banquet featured a local classic rock band with special performances by Jamey Marth and Osman Sheikh- new contact opportunities presented themselves on the dance floor too. Space does not permit summarizing the over 265 posters, 27 of which were selected for short-talk presentations. Suffice it to say that these, together with the 15 industry sponsorship booths, constituted a second nexus at the conference that nicely complemented the speaker program. Together with the three one-day Satellite Meetings (SfG-sponsored Junior Scientist Pre-Conference, CFG-sponsored Development and Application of Transformative Technologies in Glycobiology, and Industry-sponsored Glycoprotein Technologies) held before the conference, there was something sweet for every glycoscientist to taste. Next year’s conference—Integrating Glycoscience from Biology and Chemistry to Medicine—will be held jointly with the Japanese Society for Carbohydrate Research on November 16–19 at the Hilton Hawaiian Village Waikiki Beach Resort in Honolulu, Hawaii. Scheduled 10 years following the highly successful 2004 joint conference at the same venue, the 2014 version will be organized by Naoyuki Taniguchi (2014 SfG President) and Yukishige Ito (2014 JSCR President).
219
Downloaded from http://glycob.oxfordjournals.org/ at University of Michigan on June 20, 2015
regulation of the immune response (Neil Gow), and the hygiene hypothesis (Brian Cobb), emphasized that we have only seen the tip of the glycobiology iceberg in parasites and regulation of host immune responses. Having non-traditional Glycobiology speakers integrate glyco-thinking into their work will doubtless catalyze new collaborative opportunities in the future. In the International Glycoconjugate Organization-sponsored guest session on Cancer Glycobiology, heparan sulfate was assigned fundamental roles in prostate and colon cancer stem cell biology by Lianchun Wang and Minoru Fukuda. Tn-antigen and STn expression are associated with numerous tumors and Kazuaki Ohtsubo related these antigens to hypoxia, TGFbeta signaling, and EMT. John Yu emphasized the importance of glycosphingolipids and protein glycoantigens as stem cell markers that are ripe for exploitation to monitor and test as vaccines for various cancers. The vascular system is yet another organ system rich in glyco-specializations. Alan Rapraeger demonstrated the importance of receptor tyrosine kinase complexes with syndecan in angiogenesis. Jamey Marth discussed new roles for hepatic glycan receptors in management of bacterial sepsis. In a counter to dogma, Joe Lau documented how a sialyltransferase produced in the liver is transported to the bone marrow to promote hematopoiesis using sugar nucleotides secreted from platelets. Lijun Xia described new examples of the importance of O-glycosylation in podoplanin regulation of platelet activity in lymphangiogenesis and vascular integrity. In research with more direct translational implications, Karin Hoffmeister documented the importance of glycan processing enzymes in platelet birth and aging, and Paul DeAngelis rolled out a heparosan substitute for PEGylation to improve protein drug delivery. In the session on Human Disease, take-home messages included 1) a wide variety of systems, from cells to zebrafish to mice to humans, are being utilized to understand different human disorders (Stuart Kornfeld); 2) we are increasingly seeing exquisite biologic complexity related to glycans, whether it is different phenotypes of various CDGs (Hud Freeze) or the discrete roles of the different mucus layers in the colon in regulating access of microbes to host epithelia (Gunnar Hansson) or the discrimination of different cellular glycans by lectins on immune cells (Yvette van Kooyk); and 3) modification of cellular glycans will be a major goal of future therapies,
