Imperial College London

ProfessorTenFeizi

Faculty of MedicineDepartment of Surgery & Cancer

Professor and Director of the Glycosciences Laboratory
 
 
 
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Contact

 

+44 (0)20 7594 7207t.feizi

 
 
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Location

 

E518Burlington DanesHammersmith Campus

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Summary

 

Publications

Publication Type
Year
to

387 results found

Chandra N, Liu Y, Liu J-X, Fraengsmyr L, Wu N, Silva LM, Lindstrom M, Chai W, Domellof FP, Feizi T, Arnberg Net al., 2019, Sulfated glycosaminoglycans as viral decoy receptors for human adenovirus type 37, Viruses, Vol: 11, ISSN: 1999-4915

Glycans on plasma membranes and in secretions play important roles in infection by many viruses. Species D human adenovirus type 37 (HAdV-D37) is a major cause of epidemic keratoconjunctivitis (EKC) and infects target cells by interacting with sialic acid (SA)-containing glycans via the fiber knob domain of the viral fiber protein. HAdV-D37 also interacts with sulfated glycosaminoglycans (GAGs), but the outcome of this interaction remains unknown. Here, we investigated the molecular requirements of HAdV-D37 fiber knob:GAG interactions using a GAG microarray and demonstrated that fiber knob interacts with a broad range of sulfated GAGs. These interactions were corroborated in cell-based assays and by surface plasmon resonance analysis. Removal of heparan sulfate (HS) and sulfate groups from human corneal epithelial (HCE) cells by heparinase III and sodium chlorate treatments, respectively, reduced HAdV-D37 binding to cells. Remarkably, removal of HS by heparinase III enhanced the virus infection. Our results suggest that interaction of HAdV-D37 with sulfated GAGs in secretions and on plasma membranes prevents/delays the virus binding to SA-containing receptors and inhibits subsequent infection. We also found abundant HS in the basement membrane of the human corneal epithelium, which may act as a barrier to sub-epithelial infection. Collectively, our findings provide novel insights into the role of GAGs as viral decoy receptors and highlight the therapeutic potential of GAGs and/or GAG-mimetics in HAdV-D37 infection.

JOURNAL ARTICLE

Rudkin FM, Raziunaite I, Workman H, Essono S, Belmonte R, MacCallum DM, Johnson EM, Silva L, Palma AS, Feizi T, Jensen A, Erwig LP, Gow NARet al., 2019, Single human B cell-derived monoclonal anti-Candida antibodies enhance phagocytosis and protect against disseminated candidiasis (vol 9, 5288, 2018), NATURE COMMUNICATIONS, Vol: 10, ISSN: 2041-1723

JOURNAL ARTICLE

Rudkin FM, Raziunaite I, Workman H, Essono S, Belmonte R, MacCallum DM, Johnson EM, Silva LM, Palma AS, Feizi T, Jensen A, Erwig LP, Gow NARet al., 2018, Single human B cell-derived monoclonal anti-Candida antibodies enhance phagocytosis and protect against disseminated candidiasis, NATURE COMMUNICATIONS, Vol: 9, ISSN: 2041-1723

JOURNAL ARTICLE

Akune Y, Arpinar S, Silva LM, Stoll M, Palma AS, Liu Y, Ranzinger R, Feizi Tet al., 2018, CarbArrayART: Carbohydrate Array Analysis and Reporting Tool New software for glycan array for data processing, storage and presentation, Annual Meeting of the Society-for-Glycobiology (SFG), Publisher: OXFORD UNIV PRESS INC, Pages: 1034-1035, ISSN: 0959-6658

CONFERENCE PAPER

Li Z, Feizi T, 2018, The neoglycolipid (NGL) technology-based microarrays and future prospects., FEBS Lett, Vol: 592, Pages: 3976-3991

The neoglycolipid (NGL) technology is the basis of a state-of-the-art oligosaccharide microarray system, which we offer for screening analyses to the broad scientific community. We review here the sequential development of the technology and its power in pinpointing and isolating naturally occurring ligands for glycan-binding proteins (GBPs) within glycan populations. We highlight our Designer Array approach and Beam Search Array approach for generating natural glycome arrays to identify novel ligands of biological relevance. These two microarray approaches have been applied for assignments of ligands or antigens on glucan polysaccharides for effector proteins of the immune system (Dectin-1, DC-SIGN and DC-SIGNR) and carbohydrate-binding modules (CBMs) on bacterial hydrolases. We also discuss here the more recent applications to elucidate the structure of a prostate cancer- associated antigen F77 and identify ligands for adhesins of two rotaviruses, P[10] and P[19], expressed on an epithelial mucin glycoprotein.

JOURNAL ARTICLE

Chai W, Zhang Y, Mauri L, Ciampa MG, Mulloy B, Sonnino S, Feizi Tet al., 2018, Assignment by Negative-Ion Electrospray Tandem Mass Spectrometry of the Tetrasaccharide Backbones of Monosialylated Glycans Released from Bovine Brain Gangliosides, JOURNAL OF THE AMERICAN SOCIETY FOR MASS SPECTROMETRY, Vol: 29, Pages: 1308-1318, ISSN: 1044-0305

Gangliosides, as plasma membrane-associated sialylated glycolipids, are antigenic structures and they serve as ligands for adhesion proteins of pathogens, for toxins of bacteria, and for endogenous proteins of the host. The detectability by carbohydrate-binding proteins of glycan antigens and ligands on glycolipids can be influenced by the differing lipid moieties. To investigate glycan sequences of gangliosides as recognition structures, we have underway a program of work to develop a “gangliome” microarray consisting of isolated natural gangliosides and neoglycolipids (NGLs) derived from glycans released from them, and each linked to the same lipid molecule for arraying and comparative microarray binding analyses. Here, in the first phase of our studies, we describe a strategy for high-sensitivity assignment of the tetrasaccharide backbones and application to identification of eight of monosialylated glycans released from bovine brain gangliosides. This approach is based on negative-ion electrospray mass spectrometry with collision-induced dissociation (ESI-CID-MS/MS) of the desialylated glycans. Using this strategy, we have the data on backbone regions of four minor components among the monosialo-ganglioside-derived glycans; these are of the ganglio-, lacto-, and neolacto-series.

JOURNAL ARTICLE

Stappers MHT, Clark AE, Aimanianda V, Bidula S, Reid DM, Asamaphan P, Hardison SE, Dambuza IM, Valsecchi I, Kerscher B, Plato A, Wallace CA, Yuecel R, Hebecker B, Sousa MDGT, Cunha C, Liu Y, Feizi T, Brakhage AA, Kwon-Chung KJ, Gow NAR, Zanda M, Piras M, Zanato C, Jaeger M, Netea MG, Van de Veerdonk FL, Lacerda JF, Campos A, Carvalho A, Willment JA, Latge JP, Brown GDet al., 2018, Recognition of DHN-melanin by the C-type lectin, MelLec, is required for protective immunity to Aspergillus fumigatus, Publisher: OXFORD UNIV PRESS, Pages: S156-S156, ISSN: 1369-3786

CONFERENCE PAPER

Lenman A, Liaci AM, Liu Y, Frangsmyr L, Frank M, Blaum BS, Chai W, Podgorski II, Harrach B, Benko M, Feizi T, Stehle T, Arnberg Net al., 2018, Polysialic acid is a cellular receptor for human adenovirus 52, Proceedings of the National Academy of Sciences of the United States of America, Vol: 115, Pages: E4264-E4273, ISSN: 0027-8424

Human adenovirus 52 (HAdV-52) is one of only three known HAdVs equipped with both a long and a short fiber protein. While the long fiber binds to the coxsackie and adenovirus receptor, the function of the short fiber in the virus life cycle is poorly understood. Here, we show, by glycan microarray analysis and cellular studies, that the short fiber knob (SFK) of HAdV-52 recognizes long chains of α-2,8-linked polysialic acid (polySia), a large posttranslational modification of selected carrier proteins, and that HAdV-52 can use polySia as a receptor on target cells. X-ray crystallography, NMR, molecular dynamics simulation, and structure-guided mutagenesis of the SFK reveal that the nonreducing, terminal sialic acid of polySia engages the protein with direct contacts, and that specificity for polySia is achieved through subtle, transient electrostatic interactions with additional sialic acid residues. In this study, we present a previously unrecognized role for polySia as a cellular receptor for a human viral pathogen. Our detailed analysis of the determinants of specificity for this interaction has general implications for protein–carbohydrate interactions, particularly concerning highly charged glycan structures, and provides interesting dimensions on the biology and evolution of members of Human mastadenovirus G.

JOURNAL ARTICLE

Stappers MHT, Clark AE, Aimanianda V, Bidula S, Reid DM, Asamaphan P, Hardison SE, Dambuza IM, Valsecchi I, Kerscher B, Plato A, Wallace CA, Yuecel R, Hebecker B, Teixeira Sousa MDG, Cunha C, Liu Y, Feizi T, Brakhage AA, Kwon-Chung KJ, Gow NAR, Zanda M, Piras M, Zanato C, Jaeger M, Netea MG, de Veerdonk FLV, Lacerda JF, Campos A, Carvalho A, Willment JA, Latge J-P, Brown GDet al., 2018, Recognition of DHN-melanin by a C-type lectin receptor is required for immunity to Aspergillus, NATURE, Vol: 555, Pages: 382-386, ISSN: 0028-0836

Resistance to infection is critically dependent on the ability of pattern recognition receptors to recognize microbial invasion and induce protective immune responses. One such family of receptors are the C-type lectins, which are central to antifungal immunity1. These receptors activate key effector mechanisms upon recognition of conserved fungal cell-wall carbohydrates. However, several other immunologically active fungal ligands have been described; these include melanin2,3, for which the mechanism of recognition is hitherto undefined. Here we identify a C-type lectin receptor, melanin-sensing C-type lectin receptor (MelLec), that has an essential role in antifungal immunity through recognition of the naphthalene-diol unit of 1,8-dihydroxynaphthalene (DHN)-melanin. MelLec recognizes melanin in conidial spores of Aspergillus fumigatus as well as in other DHN-melanized fungi. MelLec is ubiquitously expressed by CD31+ endothelial cells in mice, and is also expressed by a sub-population of these cells that co-express epithelial cell adhesion molecule and are detected only in the lung and the liver. In mouse models, MelLec was required for protection against disseminated infection with A. fumigatus. In humans, MelLec is also expressed by myeloid cells, and we identified a single nucleotide polymorphism of this receptor that negatively affected myeloid inflammatory responses and significantly increased the susceptibility of stem-cell transplant recipients to disseminated Aspergillus infections. MelLec therefore recognizes an immunologically active component commonly found on fungi and has an essential role in protective antifungal immunity in both mice and humans.

JOURNAL ARTICLE

Liu Y, Palma AS, Ten F, Chai Wet al., 2018, Insights Into Glucan Polysaccharide Recognition Using Glucooligosaccharide Microarrays With Oxime-Linked Neoglycolipid Probes, CHEMICAL GLYCOBIOLOGY, PT B: MONITORING GLYCANS AND THEIR INTERACTIONS, Editors: Imperiali, Publisher: ELSEVIER ACADEMIC PRESS INC, Pages: 139-167

BOOK CHAPTER

Akune Y, Arpinar S, Stoll M, Silva LM, Palma AS, Liu Y, Ranzinger R, Feizi Tet al., 2017, New software for glycan array for data processing, storage and presentation, Annual Meeting of the Society-for-Glycobiology, Publisher: OXFORD UNIV PRESS INC, Pages: 1204-1204, ISSN: 0959-6658

CONFERENCE PAPER

Liu Y, Catera R, Gao C, Yan J, Magli A, Allen SL, Rai K, Chu CC, Stamatopoulos K, Chiorazzi N, Kolitz JE, Feizi Tet al., 2017, The (auto)antigen specificities of B cell receptor immunoglobulins from CLL stereotyped subset 4 are positively and negatively selected by structural elements introduced by somatic mutation and isotype class switching, Publisher: TAYLOR & FRANCIS LTD, Pages: 80-81, ISSN: 1042-8194

CONFERENCE PAPER

Li Z, Gao C, Zhang Y, Palma A, Childs R, Silva L, Liu Y, Jiang X, Liu Y, Chai W, Feizi Tet al., 2017, O-Glycome beam search arrays for carbohydrate ligand discovery, Molecular and Cellular Proteomics, Vol: 17, Pages: 121-133, ISSN: 1535-9476

O-glycosylation is a post-translational modification of proteins crucial to molecular mechanisms in health and disease. O-glycans are typically highly heterogeneous. The involvement of specific O-glycan sequences in many bio-recognition systems is yet to be determined due to a lack of efficient methodologies. We describe here a targeted microarray approach: O-glycome beam search that is both robust and efficient for O-glycan ligand-discovery. Substantial simplification of the complex O-glycome profile and facile chromatographic resolution is achieved by arraying O-glycans as branches, monitoring by mass spectrometry, focusing on promising fractions, and on-array immuno-sequencing. This is orders of magnitude more sensitive than traditional methods. We have applied beam search approach to porcine stomach mucin and identified extremely minor components previously undetected within the O-glycome of this mucin that are ligands for the adhesive proteins of two rotaviruses. The approach is applicable to O-glycome recognition studies in a wide range of biological settings to give insights into glycan recognition structures in natural microenvironments.

JOURNAL ARTICLE

Panagos C, Moss C, Bavington C, Mulloy B, Feizi T, Chai W, Woods R, Uhrin Det al., 2017, Analysis of the 3D structure of fucosylated chondroitin sulfate from H. forskali and its interaction with selectins, 254th National Meeting and Exposition of the American-Chemical-Society (ACS) on Chemistry's Impact on the Global Economy, Publisher: AMER CHEMICAL SOC, ISSN: 0065-7727

CONFERENCE PAPER

Catera R, Liu Y, Gao C, Yan X-J, Magli A, Allen SL, Kolitz JE, Rai KR, Chu CC, Feizi T, Stamatopoulos K, Chiorazzi Net al., 2017, Binding of CLL Subset 4 B Cell Receptor Immunoglobulins to Viable Human Memory B Lymphocytes Requires a Distinctive IGKV Somatic Mutation, MOLECULAR MEDICINE, Vol: 23, Pages: 1-12, ISSN: 1076-1551

JOURNAL ARTICLE

Liu Y, McBride R, Stoll M, Palma AS, Silva L, Agravat S, Aoki-Kinoshita KF, Campbell MP, Costello CE, Dell A, Haslam SM, Karlsson NG, Khoo K-H, Kolarich D, Novotny M, Packer NH, Ranzinger R, Rapp E, Rudd PM, Struwe WB, Tiemeyer M, Wells L, York WS, Zaia J, Kettner C, Paulson JC, Feizi T, Smith DFet al., 2016, The Minimum Information Required for a Glycomics Experiment (MIRAGE) project: improving the standards for reporting glycan microarray-based data, Glycobiology, Vol: 27, Pages: 280-284, ISSN: 1460-2423

MIRAGE (Minimum Information Required for A Glycomics Experiment) is an initiative that was created by experts in the fields of glycobiology, glycoanalytics, and glycoinformatics to produce guidelines for reporting results from the diverse types of experiments and analyses used in structural and functional studies of glycans in the scientific literature. As a sequel to the guidelines for sample preparation (Struwe et al. 2016, Glycobiology, 26, 907-910) and mass spectrometry (MS) data (Kolarich et al. 2013, Mol. Cell Proteomics. 12, 991-995), here we present the first version of guidelines intended to improve the standards for reporting data from glycan microarray analyses. For each of eight areas in the workflow of a glycan microarray experiment, we provide guidelines for the minimal information that should be provided in reporting results. We hope that the MIRAGE glycan microarray guidelines proposed here will gain broad acceptance by the community, and will facilitate interpretation and reproducibility of the glycan microarray results with implications in comparison of data from different laboratories and eventual deposition of glycan microarray data in international databases.

JOURNAL ARTICLE

Correia VG, Bras JLA, Liu Y, Silva L, Zhang Y, Pinheiro BA, Romao MJ, Carvalho AL, Chai W, Fontes CMGA, Feizi T, Palma ASet al., 2016, An integrative strategy to decipher glycan recognition in the human gut microbiome, Annual Meeting of the Society-for-Glycobiology, Publisher: OXFORD UNIV PRESS INC, Pages: 1398-1399, ISSN: 0959-6658

CONFERENCE PAPER

Bartels MF, Winterhalter PR, Yu J, Liu Y, Lommel M, Möhrlen F, Hu H, Feizi T, Westerlind U, Ruppert T, Strahl Set al., 2016, Protein O-Mannosylation in the Murine Brain: Occurrence of Mono-O-Mannosyl Glycans and Identification of New Substrates, PLOS One, Vol: 11, ISSN: 1932-6203

Protein O-mannosylation is a post-translational modification essential for correct development of mammals. In humans, deficient O-mannosylation results in severe congenital muscular dystrophies often associated with impaired brain and eye development. Although various O-mannosylated proteins have been identified in the recent years, the distribution of O-mannosyl glycans in the mammalian brain and target proteins are still not well defined. In the present study, rabbit monoclonal antibodies directed against the O-mannosylated peptide YAT(α1-Man)AV were generated. Detailed characterization of clone RKU-1-3-5 revealed that this monoclonal antibody recognizes O-linked mannose also in different peptide and protein contexts. Using this tool, we observed that mono-O-mannosyl glycans occur ubiquitously throughout the murine brain but are especially enriched at inhibitory GABAergic neurons and at the perineural nets. Using a mass spectrometry-based approach, we further identified glycoproteins from the murine brain that bear single O-mannose residues. Among the candidates identified are members of the cadherin and plexin superfamilies and the perineural net protein neurocan. In addition, we identified neurexin 3, a cell adhesion protein involved in synaptic plasticity, and inter-alpha-trypsin inhibitor 5, a protease inhibitor important in stabilizing the extracellular matrix, as new O-mannosylated glycoproteins.

JOURNAL ARTICLE

Zhang H, Palma AS, Zhang Y, Childs RA, Liu Y, Mitchell DA, Guidolin LS, Weigel W, Mulloy B, Ciocchini AE, Feizi T, Chai Wet al., 2016, Generation and characterization of β1,2-gluco-oligosaccharide probes from Brucella abortus cyclic β-glucan and their recognition by C-type lectins of the immune system, Glycobiology, Vol: 26, Pages: 1086-1096, ISSN: 1460-2423

The β1,2-glucans produced by bacteria are important in invasion, survival andimmunomodulation in infected hosts be they mammals or plants. However, there has been alack of information on proteins which recognize these molecules. This is partly due to theextremely limited availability of the sequence-defined oligosaccharides and derived probesfor use in the study of their interactions. Here we have used the cyclic β1,2-glucan (CβG) ofthe bacterial pathogen Brucella abortus, after removal of succinyl side chains, to preparelinearized oligosaccharides which were used to generate microarrays. We describe optimizedconditions for partial depolymerization of the cyclic glucan by acid hydrolysis and conversionof the β1,2-gluco-oligosaccharides, with degrees of polymerization 2-13, to neoglycolipids forthe purpose of generating microarrays. By microarray analyses we show that the C-type lectinreceptor DC-SIGNR, like the closely related DC-SIGN we investigated earlier, binds to theβ1,2-gluco-oligosaccharides, as does the soluble immune effector serum mannose-bindingprotein. Exploratory studies with DC-SIGN are suggestive of the recognition also of the intactCβG by this receptor. These findings open the way to unravelling mechanisms ofimmunomodulation mediated by β1,2-glucans in mammalian systems.

JOURNAL ARTICLE

Struwe WB, Agravat S, Aoki-Kinoshita KF, Campbell MP, Costello CE, Dell A, Ten Feizi, Haslam SM, Karlsson NG, Khoo KH, Kolarich D, Liu Y, McBride R, Novotny MV, Packer NH, Paulson JC, Rapp E, Ranzinger R, Rudd PM, Smith DF, Tiemeyer M, Wells L, York WS, Zaia J, Kettner Cet al., 2016, The minimum information required for a glycomics experiment (MIRAGE) project: sample preparation guidelines for reliable reporting of glycomics datasets., Glycobiology, Vol: 26, Pages: 907-910, ISSN: 0959-6658

The minimum information required for a glycomics experiment (MIRAGE) project was established in 2011 to provide guidelines to aid in data reporting from all types of experiments in glycomics research including mass spectrometry (MS), liquid chromatography, glycan arrays, data handling and sample preparation. MIRAGE is a concerted effort of the wider glycomics community that considers the adaptation of reporting guidelines as an important step towards critical evaluation and dissemination of datasets as well as broadening of experimental techniques worldwide. The MIRAGE Commission published reporting guidelines for MS data and here we outline guidelines for sample preparation. The sample preparation guidelines include all aspects of sample generation, purification and modification from biological and/or synthetic carbohydrate material. The application of MIRAGE sample preparation guidelines will lead to improved recording of experimental protocols and reporting of understandable and reproducible glycomics datasets.

JOURNAL ARTICLE

Liu Y, Ramelot TA, Huang P, Liu Y, Li Z, Feizi T, Zhong W, Wu FT, Tan M, Kennedy MA, Jiang Xet al., 2016, Glycan specificity of P[19] rotavirus and comparison with those of other related P genotypes, Journal of Virology, Vol: 90, Pages: 9983-9996, ISSN: 1098-5514

The P[19] genotype belongs to the P[II] genogroup of group A rotaviruses (RVs). However, unlike the other P[II] RVs that mainly infects humans, P[19] RVs commonly infect animals (porcine), making P[19] unique to study RV diversity and host ranges. Through in vitro binding assays and saturation transfer difference (STD) NMR, we found that P[19] could bind mucin cores 2, 4, and 6, as well as type 1 histo-blood group antigens (HBGAs). The common sequences of these glycans serve as minimal binding units, while additional residues, such as the A, B, H, and Lewis epitopes of the type 1 HBGAs, can further define the binding outcomes and therefore, likely the host ranges for P[19] RVs. This complex binding property of P[19] is shared with those of the other three P[II] RVs (P[4], P[6] and P[8]) in that all of them recognized the type 1 HBGA precursor, although P[4] and P[8], but not P[6], also bind to mucin cores. Moreover, while essential for P[4] and P[8] binding, the addition of the Lewis epitope blocked P[6] and P[19] binding to type 1 HBGAs. Chemical shift NMR of P[19] VP8* identified a ligand binding interface that has shifted away from the known RV P-genotype binding sites but is conserved among all P[II] RVs and two P[I] RVs (P[10] and P[12]), suggesting an evolutionary connection among these human and animal RVs. Taken together, these data are important for hypotheses on potential mechanisms for RV diversity, host ranges, and cross-species transmission. IMPORTANCE: In this study, we found that this P[19] strain and other P[II] RVs recognize mucin cores and the type 1 HBGA precursors as the minimal functional units and that additional saccharides adjacent to these units can alter binding outcomes and thereby possibly host ranges. These data may help to explain why some P[II] RVs, such as P[6] and P[19], commonly infect animals but rarely humans, while others, such as the P[4] and P[8] RVs, mainly infect humans and are predominant over other P genotypes. Elucidation

JOURNAL ARTICLE

Mulloy B, Wu N, Gyapon-Quast F, Lin L, Zhang F, Pickering MC, Linhardt RJ, Feizi T, Chai Wet al., 2016, Abnormally high content of free glucosamine residues identified in a preparation of commercially available porcine intestinal heparan sulfate, Analytical Chemistry, Vol: 88, Pages: 6648-6652, ISSN: 1520-6882

Heparan sulfate (HS) polysaccharides are ubiquitous in animal tissues as components of proteoglycans, and they participate in many important biological processes. HS carbohydrate chains are complex and can contain rare structural components such as N-unsubstituted glucosamine (GlcN). Commercially available HS preparations have been invaluable in many types of research activities. In the course of preparing microarrays to include probes derived from HS oligosaccharides, we found an unusually high content of GlcN residue in a recently purchased batch of porcine intestinal mucosal HS. Composition and sequence analysis by mass spectrometry of the oligosaccharides obtained after heparin lyase III digestion of the polysaccharide indicated two and three GlcN in the tetrasaccharide and hexasaccharide fractions, respectively. 1H NMR of the intact polysaccharide showed that this unusual batch differed strikingly from other HS preparations obtained from bovine kidney and porcine intestine. The very high content of GlcN (30%) and low content of GlcNAc (4.2%) determined by disaccharide composition analysis indicated that N-deacetylation and/or N-desulfation may have taken place. HS is widely used by the scientific community to investigate HS structures and activities. Great care has to be taken in drawing conclusions from investigations of structural features of HS and specificities of HS interaction with proteins when commercial HS is used without further analysis. Pending the availability of a validated commercial HS reference preparation, our data may be useful to members of the scientific community who have used the present preparation in their studies.

JOURNAL ARTICLE

Parker L, Wharton SA, Martin SR, Cross K, Lin Y, Liu Y, Feizi T, Daniels RS, McCauley JWet al., 2016, Effects of egg-adaptation on receptor-binding and antigenic properties of recent influenza A (H3N2) vaccine viruses, Journal of General Virology, Vol: 97, Pages: 1333-1344, ISSN: 1465-2099

Influenza A virus (subtype H3N2) causes seasonal human influenza and is included as a component of influenza vaccines. The majority of vaccine viruses are isolated and propagated in eggs, which commonly results in amino acid substitutions in the haemagglutinin (HA) glycoprotein. These substitutions can affect virus receptor-binding and alter virus antigenicity, thereby, obfuscating the choice of egg-propagated viruses for development into candidate vaccine viruses. To evaluate the effects of egg-adaptive substitutions seen in H3N2 vaccine viruses on sialic acid receptor-binding, we carried out quantitative measurement of virus receptor-binding using surface biolayer interferometry with haemagglutination inhibition (HI) assays to correlate changes in receptor avidity with antigenic properties. Included in these studies was a panel of H3N2 viruses generated by reverse genetics containing substitutions seen in recent egg-propagated vaccine viruses and corresponding cell culture-propagated wild-type viruses. These assays provide a quantitative approach to investigating the importance of individual amino acid substitutions in influenza receptor-binding. Results show that viruses with egg-adaptive HA substitutions R156Q, S219Y, and I226N, have increased binding avidity to α2,3-linked receptor-analogues and decreased binding avidity to α2,6-linked receptor-analogues. No measurable binding was detected for the viruses with amino acid substitution combination 156Q+219Y and receptor-binding increased in viruses where egg-adaptation mutations were introduced into cell culture-propagated virus. Substitutions at positions 156 and 190 appeared to be primarily responsible for low reactivity in HI assays with post-infection ferret antisera raised against 2012–2013 season H3N2 viruses. Egg-adaptive substitutions at position 186 caused substantial differences in binding avidity with an insignificant effect on antigenicity.

JOURNAL ARTICLE

Cecílio NT, Carvalho FC, Liu Y, Moncrieffe M, Buranello PADA, Zorzetto-Fernandes AL, Luche DD, Hanna ES, Soares SG, Feizi T, Gay NJ, Goldman MHS, Roque-Barreira MCet al., 2016, Yeast expressed ArtinM shares structure, carbohydrate recognition, and biological effects with native ArtinM., Int J Biol Macromol, Vol: 82, Pages: 22-30

Recent advances in glycobiology have revealed the essential role of lectins in deciphering the glycocodes at the cell surface to generate important biological signaling responses. ArtinM, a d-mannose-binding lectin isolated from the seeds of jackfruit (Artocarpus heterophyllus), is composed of 16 kDa subunits that are associated to form a homotetramer. Native ArtinM (n-ArtinM) exerts immunomodulatory and regenerative effects, but the potential pharmaceutical applicability of the lectin is highly limited by the fact that its production is expensive, laborious, and impossible to be scaled up. This led us to characterize a recombinant form of the lectin obtained by expression in Saccharomyces cerevisiae (y-ArtinM). In the present study, we demonstrated that y-ArtinM is similar to n-ArtinM in subunit arrangement, oligomerization and carbohydrate binding specificity. We showed that y-ArtinM can exert n-ArtinM biological activities such as erythrocyte agglutination, stimulation of neutrophil migration and degranulation, mast cell degranulation, and induction of interleukin-12 and interleukin-10 production by macrophages. In summary, the expression of ArtinM in yeast resulted in successful production of an active, recombinant form of ArtinM that is potentially useful for pharmaceutical application.

JOURNAL ARTICLE

Liu Y, Cecilio NT, Carvalho FC, Roque Barreira MC, Feizi Tet al., 2015, Glycan microarray analysis of the carbohydrate-recognition specificity of native and recombinant forms of the lectin ArtinM, Data in Brief, Vol: 5, Pages: 1035-1047, ISSN: 2352-3409

This article contains data related to the researc.h article entitled “Yeast-derived ArtinM shares structure, carbohydrate recognition, and biological effects with native ArtinM” by Cecílio et al. (2015) [1]. ArtinM, a D-mannose-binding lectin isolated from the seeds of Artocarpus heterophyllus, exerts immunomodulatory and regenerative activities through its Carbohydrate Recognition Domain (CRD) (Souza et al., 2013; Mariano et al., 2014 [2] and [3]). The limited availability of the native lectin (n-ArtinM) led us to characterize a recombinant form of the protein, obtained by expression in Saccharomyces cerevisiae (y-ArtinM). We compared the carbohydrate-binding specificities of y-ArtinM and n-ArtinM by analyzing the binding of biotinylated preparations of the two lectin forms using a neoglycolipid (NGL)-based glycan microarray. Data showed that y-ArtinM mirrored the specificity exhibited by n-ArtinM.

JOURNAL ARTICLE

Gao C, Zhang Y, Liu Y, Ten F, Chai Wet al., 2015, Negative-Jon Electrospray Tandem Mass Spectrometry and Microarray Analyses of Developmentally Regulated Antigens Based on Type 1 and Type 2 Backbone Sequences, Analytical Chemistry, Vol: 87, Pages: 11871-11878, ISSN: 1520-6882

Type 1 (Galβ1-3GlcNAc) and type 2 (Galβ1-4GlcNAc) sequences are constituents of the backbones of alarge family of glycans of glycoproteins and glycolipids whosebranching and peripheral substitutions are developmentallyregulated. It is highly desirable to have microsequencingmethods that can be used to precisely identify and monitorthese oligosaccharide sequences with high sensitivity. Negative-ionelectrospray tandem mass spectrometry withcollision-induced dissociation has been used for characterizationof branching points, peripheral substitutions, andpartial assignment of linkages in reducing oligosaccharides. Wenow extend this method to characterizing entire sequences oflinear type 1 and type 2 chain-based glycans, focusing on thetype 1 and type 2 units in the internal regions including the linkages connecting type 1 and type 2 disaccharide units. We applythe principles to sequence analysis of closely related isomeric oligosaccharides and demonstrate by microarray analyses distinctbinding activities of antibodies and a lectin toward various combinations of type 1 and 2 units joined by 1,3- and 1,6-linkages.These sequence-specific carbohydrate-binding proteins are in turn valuable tools for detecting and distinguishing the type 1 andtype 2-based developmentally regulated glycan sequences.

JOURNAL ARTICLE

Silva L, Childs RA, Palma AS, Chai W, Feizi T, Liu Yet al., 2015, Influence of carrier lipid composition on glycan recognition in NGL-based microarrays, Annual Meeting of the Society-for-Glycobiology on Glycobiology - Accelerating Impact across the Biomedical Sciences, Publisher: OXFORD UNIV PRESS INC, Pages: 1260-1260, ISSN: 0959-6658

CONFERENCE PAPER

Feizi TEN, Haltiwanger RS, 2015, Editorial overview: Carbohydrate-protein interactions and glycosylation: Glycan synthesis and recognition: finding the perfect partner in a sugar-coated life., Curr Opin Struct Biol, Vol: 34, Pages: vii-ix

Oligosaccharides expressed on the surface of cells and in biological fluids as glycoproteins, glycolipids, proteoglycans and polysaccharides can be recognized by partner proteins, and these interactions have been shown to mediate fundamental biological events such as occur in the immune system, signal transduction, development and cancer metastasis. The specificities of these partner proteins (lectins) for their glycan ligands are determined by factors such as glycan composition, shape and density of expression and the involvement of the aglycone moiety as part of the recognition motif. There is increasing knowledge on the mechanisms of these interactions as new secondary binding sites continue to be elucidated adding to the functional awareness of sugar-binding proteins. This issue focuses on recent advances in understanding how C-type lectins in the immune system work, how novel motifs involving asymmetric glycan branch recognition and protein-protein interactions influence critical biological functions including signal transduction and bactericidal pore formation, recent studies on novel glycan-binding proteins produced by bacteriophage, analysis of the interactions between heparin/heparan sulphate and their binding proteins, and recent findings on the molecular interactions between chondroitin-dermatan sulphate and various bioactive protein components. We conclude with a review on a recent fascinating class of processive enzymes responsible for synthesis of high-molecular weight extracellular polysaccharides such as hyaluronic acid, chitin and alginate.

JOURNAL ARTICLE

Hirose H, Tamai H, Gao C, Imamuru A, Ishida H, Feizi T, Kiso Met al., 2015, Total syntheses of disulphated glycosphingolipid SB1a and the related monosulphated SM1a, Organic and Biomolecular Chemistry, Vol: 13, Pages: 11105-11117, ISSN: 1472-7781

Total syntheses of two natural sulphoglycolipids, disulphated glycosphingolipid SB1a and the structurally related monosulphated SM1a, are described. They have common glycan sequences and ceramide moieties and are associated with human epithelial carcinomas. The syntheses featured efficient glycan assembly and the glucosyl ceramide cassette as a versatile building block. The binding of the synthetic sulphoglycolipids by the carcinoma-specific monoclonal antibody AE3 was investigated using carbohydrate microarray technology.

JOURNAL ARTICLE

Gyapon-Quast F, Chai W, Liu Y, Pickering MC, Feizi Tet al., 2015, Complement factor H-related protein 5 binding to heparan sulphate increases factor H de-regulation in vitro, 15th European Meeting on Complement in Human Disease (EMCHD), Publisher: PERGAMON-ELSEVIER SCIENCE LTD, Pages: 141-141, ISSN: 0161-5890

CONFERENCE PAPER

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