Core Support for Collaborative Research in Glycobiology

Lead Research Organisation: Imperial College London
Department Name: Life Sciences

Abstract

The genome sequencing projects of the past two decades have yielded the startling revelation that the total number of genes in humans is not very different from many model organisms such as worms and plants. This discovery served to highlight the fact that substantial amplification of genomic information occurs after genes are translated into proteins. Glycosylation, which involves the addition of sugars to selected protein amino acid side-chains, is the most abundant and arguably the most important of these post-translational modifications. Indeed, all cells are coated with a sugar-rich layer called the glycocalyx. Chains of sugars, called glycans, on the periphery of the glycocalyx bind to specific sugar-recognition proteins, called lectins, on partner cells. Many important biological processes depend on the ability of cells to appropriately communicate with each other via these sugar-lectin interactions and to respond accordingly. For example, lectins on the surfaces of viruses and bacteria are known to recognise sugars on target cells and attach to them as the first step of infection. Conversely the adaptive immune system is triggered when sugars on the surfaces of pathogens bind to lectins expressed by cells of the host immune system. Although these examples of glycan-lectin recognition are now relatively well understood, many biological processes that are likely to be similarly controlled by glycan-lectin interactions remain enigmatic. For example, how do immune cells in the gut distinguish between beneficial and harmful microbes, and how does a developing foetus escape rejection by the mother despite being half "foreign"? Pivotal to learning how glycans function in these processes is knowing their structures. We specialize in glycan structural determination using a sophisticated analytical technique called mass spectrometry. We do this in collaboration with dozens of scientists from many biological disciplines both nationally and internationally, who are working with us to explore glycan-lectin structure/function relationships. We are particularly interested in characterizing the glycans that are involved in host microbe interactions, in immune regulation and in mediating recognition events during mammalian reproduction. As well as contributing to fundamental understanding of glycan function, we aim to provide structural data to underpin the identification of targets for new drugs and vaccines for the control of pathogens and parasites. We anticipate that our studies of the glycobiology of mammalian fertilization and reproduction will open up new avenues for natural contraception as well as helping infertile couples. Another of our goals is to understand the pathways involved in regulating glycosylation. This is important, not only because altered glycosylation is associated with many chronic health and aging problems, but also because this knowledge will assist the efficient production of well defined glycoprotein biopharmaceuticals. As well as being important constituents of glycoproteins, sugars are the major building blocks of the polysaccharides that constitute the walls of plant cells. There is an urgent need to better understand the biological processes involved in plant cell wall assembly if the potential of biomass as a renewable energy resource and an alternative to fossil fuels for the production of high value chemicals is to be fully realised. We aim to work with plant scientists in the UK and Australia to elucidate the molecular mechanisms of cell wall polysaccharide biosynthesis. Our analytical methods generate large volumes of complex data, so another of our objectives is to create glycoinformatic tools to assist and speed up data interpretation and annotation, and these tools will be made available to the scientific community. We will also develop and populate openly available databases with our glycan structural data, a resource that will benefit scientists from many disciplines around the world.

Technical Summary

We request core support for our world-class mass spectrometry laboratory to enable us to continue to undertake glycobiological research of relevance to the BBSRC priority areas of basic bioscience underpinning health, food security and bioenergy. We are working with more than thirty collaborators in the UK and abroad with the overarching goal of providing a molecular understanding of (i) biological events in which glycan-lectin recognition plays a central role, and (ii) regulation of glycosylation pathways in the biosynthesis of eukaryotic and prokaryotic glycoproteins, bacterial lipopolysaccharides and plant cell wall polysaccharides. A key objective of our research is the continued enhancement of our glycomic and glycoproteomic platforms which are based on the integration of ultra-high sensitivity mass spectrometry with carbohydrate and protein chemistry. We aim to continue to develop open source informatic tools for improving data analysis and to substantially improve and populate public data resources. We will apply our technologies to projects in the following areas: (a) the glycobiology of host/pathogen interactions including characterising glycoconjugates of pathogens and parasites with an important aim being to identify potential vaccine candidates; (b) defining the roles of glycans in regulating host-virus interactions, including characterisation of viral glycoproteins as well as the glycan and lectin receptors of their hosts; (c) exploring how host glycosylation influences the gut microbiome thereby contributing to research into human nutrition and health; (d) investigating the regulation of mammalian glycosylation via the study of metabolic dysfunction; (e) contributing to the glycobiology of mammalian fertilization and reproduction including hunting for the egg binding protein on human sperm and defining structure/function relationships in glycodelin glycoforms; (f) defining the molecular mechanisms of cell wall polysaccharide assembly in higher plants.

Planned Impact

The programme of work outlined in this proposal will have considerable academic, economic and societal impact. It will not only lead to new knowledge and scientific advancement for the numerous collaborating scientists detailed in the proposal, but will benefit the wider academic community who have interests in cell-cell interactions, pathogen virulence, immune suppression, adaptive immunity, health and nutrition, the gut microbiome, human fertilization and reproduction, metabolic disorders, bioprocessing and plant sciences. Non-academic beneficiaries of our research will include the biotech and pharma industries, plus the biofuels and industrial biotechnology sectors. Other beneficiaries are the Animal Health and Veterinary Laboratories Agency, who will exploit our research outputs to improve their assays for diagnosis of porcine and bovine brucellosis, and the Defence Science and Technology Laboratory, whose vaccine programmes will benefit from our enhanced methodologies for bacterial LPS analysis. Many of the BBSRC's priority areas have an urgent need for glycobiological skills. We will address this issue by training and delivering highly skilled glycobiology researchers in our GlycoTRIC Centre. We will continue to develop and improve glycomic and glycoproteomic technologies, especially our glycoinformatic tools and data depositories, which will lead to worldwide academic advancements. Our research will give outputs that will benefit and impact on society in general. For example our studies of the glycobiology of host/pathogen interactions will lead to the development of new treatments and vaccines against a wide range of human and animal diseases which will lead to better human and animal health and an improved quality of life and food security. Our studies of the glycobiology of mammalian fertilization and reproduction will assist women suffering from infertility and recurrent pregnancy loss and potentially also have an impact on livestock production. Our studies of plant cell wall biosynthesis will provide a better fundamental understanding of the processes involved and therefore facilitate the exploitation of biomass for the production of biofuels and high value chemicals. Outputs from our glycomic and glycoproteomic method development will have an impact on UK and international industry therefore contributing towards wealth creation and economic prosperity. Our research on defining post-translational modifications of proteins is of special interest to both the pharma and biotech industries, not least because of the importance of glycosylation in many therapeutic proteins currently under development. Our mass spectrometric method development has been pioneering, and a number of our original discoveries including the concept of MS peptide and glycopeptide mapping now feature in the International Committee on Harmonisation (ICH) Guidelines for Test Procedures and Acceptance Criteria for Biotechnology Products and in the Points to Consider advice on Characterising Monclonal Antibodies, thus accelerating and simplifying the characterisation of Biopharmaceutical Products with considerable financial implications of benefit to industry and to the end-consumer in society. Our research outputs will benefit MS instrument manufacturers in the UK and abroad. Such companies can exploit our glycoinformatics developments by incorporating the tools we design into their commercial analysis platforms, benefiting from reduced development costs and increased sales as a result of the new features gained. Bruker Daltronics recently benefited in this way by incorporating our GlycoWorkbench tool into their commercial software.

Organisations

Publications

10 25 50
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Aoki-Kinoshita K (2016) GlyTouCan 1.0--The international glycan structure repository. in Nucleic acids research

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Chen Q (2016) Evidence for Differential Glycosylation of Trophoblast Cell Types. in Molecular & cellular proteomics : MCP

 
Description Major achievements include: (1) via our collaborations with bioscientists worldwide we are opening up new fields of glycobiology; (2) we are developing improved analytical glycomic and glycoproteomic methodologies; and (3) we are disseminating know-how and expertise via the training activities of our glycoTRIC Centre. Our structural outputs from over fifty collaborations have yielded new understanding of glycan involvement in pathogen infection and self/non-self recognition in human reproduction, as well as contributing to the development of global glycosylation inhibitors which have tharapeutic potential.
Exploitation Route All our research outputs are being exploited by our collaborators to push forward their own research.
Global glycosylation inhibitors could potentially treat diseases such as autoimmunity, cancer metastasis and influenza.
Our pathogen research is facilitating the glyco-engineering of glycoconjugate vaccines.
Sectors Agriculture, Food and Drink,Healthcare,Pharmaceuticals and Medical Biotechnology

 
Description 1.Our open source glycoinformatic tools have been downloaded and utilized by a wide range of commercial users. These included These included large pharma and other biomedical related companies. The tools have been used to improve the accuracy and speed of the analysis of carbohydrate containing biomolecules and biopharmaceuticals. These new medical drugs produced using industrial biotechnology processes, are one of the fastest growing sectors of the pharmaceutical industry. Many important biopharmaceuticals, such as therapeutic antibodies with commercial sales in the billions of pounds are glycoproteins. The type of sugar molecule on the biopharmaceuticals can greatly affect their functional properties. This can greatly affect the potential therapeutic value of the products and thus requires accurate and efficient analysis. The tools have also been utilized by manufacturers of mass spectrometry equipment to improve the capabilities of the software they develop to assist in the analysis of the data generated by their instruments. 2. Our glycoimmunology basic research has been exploited by collaborators at the University of Missouri who have developed a novel cancer vaccine therapy that was licensed to Elias Animal Health in December 2018
First Year Of Impact 2014
Sector Agriculture, Food and Drink,Education,Healthcare,Culture, Heritage, Museums and Collections,Pharmaceuticals and Medical Biotechnology
Impact Types Societal,Economic

 
Description Responsive mode
Amount £1,728,000 (GBP)
Funding ID BB/K016164/1 
Organisation Biotechnology and Biological Sciences Research Council (BBSRC) 
Sector Public
Country United Kingdom
Start 07/2013 
End 06/2017
 
Description sLoLa
Amount £4,281,288 (GBP)
Funding ID BB/N001591/1 
Organisation Biotechnology and Biological Sciences Research Council (BBSRC) 
Sector Public
Country United Kingdom
Start 04/2016 
End 03/2021
 
Description An in vivo functional screen identifies ST6GalNAc2 sialyltransferase as a breast cancer metastasis suppressor 
Organisation Institute of Cancer Research UK
Department Breakthrough Toby Robins Breast Cancer Research Centre
Country United Kingdom 
Sector Academic/University 
PI Contribution Mass spectrometric structural analysis of biologically important biomolecules. Intellectual input into experimental design, data interpretation and biological relevance of project outcomes.
Collaborator Contribution Intellectual input into experimental design, data interpretation and biological relevance of project outcomes.
Impact An in vivo functional screen identifies ST6GalNAc2 sialyltransferase as a breast cancer metastasis suppressor. Murugaesu N, Iravani M, van Weverwijk A, Ivetic A, Johnson DA, Antonopoulos A, Fearns A, Jamal-Hanjani M, Sims D, Fenwick K, Mitsopoulos C, Gao Q, Orr N, Zvelebil M, Haslam SM, Dell A, Yarwood H, Lord CJ, Ashworth A, Isacke CM. Cancer Discov. 2014 Mar;4(3):304-17. doi: 10.1158/2159-8290.CD-13-0287.
Start Year 2013
 
Description Bovine Herpesvirus 4 Modulates Its ß-1,6-N-Acetylglucosaminyltransferase Activity through Alternative Splicing 
Organisation University of Liege
Department Laboratory of Immunology
Country Belgium 
Sector Academic/University 
PI Contribution Mass spectrometric structural analysis of biologically important biomolecules. Intellectual input into experimental design, data interpretation and biological relevance of project outcomes.
Collaborator Contribution Intellectual input into experimental design, data interpretation and biological relevance of project outcomes.
Impact Bovine Herpesvirus 4 Modulates Its ß-1,6-N-Acetylglucosaminyltransferase Activity through Alternative Splicing. Lété C, Markine-Goriaynoff N, Machiels B, Pang PC, Xiao X, Canis K, Suzuki M, Fukuda M, Dell A, Haslam SM, Vanderplasschen A, Gillet L. J Virol. 2015 Dec 9;90(4):2039-51. doi: 10.1128/JVI.01722-15.
Start Year 2014
 
Description Cellular O-Glycome Reporter/Amplification to explore O-glycans of living cells 
Organisation Harvard University
Department Department of Surgery
Country United States 
Sector Hospitals 
PI Contribution Mass spectrometric structural analysis of biologically important biomolecules. Intellectual input into experimental design, data interpretation and biological relevance of project outcomes.
Collaborator Contribution Intellectual input into experimental design, data interpretation and biological relevance of project outcomes.
Impact Cellular O-Glycome Reporter/Amplification to explore O-glycans of living cells. Kudelka MR, Antonopoulos A, Wang Y, Duong DM, Song X, Seyfried NT, Dell A, Haslam SM, Cummings RD, Ju T. Nat Methods. 2016 Jan;13(1):81-6. doi: 10.1038/nmeth.3675.
Start Year 2015
 
Description Characterization of H type 1 and type 1 N-acetyllactosamine glycan epitopes on ovarian cancer specifically recognized by the anti-glycan monoclonal antibody mAb-A4 
Organisation Bioprocessing Technology Institute
Country Singapore 
Sector Public 
PI Contribution Mass spectrometric structural analysis of biologically important biomolecules. Intellectual input into experimental design, data interpretation and biological relevance of project outcomes.
Collaborator Contribution Intellectual input into experimental design, data interpretation and biological relevance of project outcomes.
Impact Characterization of H type 1 and type 1 N-acetyllactosamine glycan epitopes on ovarian cancer specifically recognized by the anti-glycan monoclonal antibody mAb-A4. Choo M, Tan HL, Ding V, Castangia R, Belgacem O, Liau B, Hartley-Tassell L, Haslam SM, Dell A, Choo A. J Biol Chem. 2017 Feb 6. pii: jbc.M116.768887. doi: 10.1074/jbc.M116.768887.
Start Year 2016
 
Description Developing the IVIG biomimetic, hexa-Fc, for drug and vaccine applications 
Organisation Liverpool School of Tropical Medicine
Country United Kingdom 
Sector Academic/University 
PI Contribution Mass spectrometric structural analysis of biologically important biomolecules. Intellectual input into experimental design, data interpretation and biological relevance of project outcomes.
Collaborator Contribution Intellectual input into experimental design, data interpretation and biological relevance of project outcomes.
Impact Developing the IVIG biomimetic, hexa-Fc, for drug and vaccine applications. Czajkowsky DM, Andersen JT, Fuchs A, Wilson TJ, Mekhaiel D, Colonna M, He J, Shao Z, Mitchell DA, Wu G, Dell A, Haslam S, Lloyd KA, Moore SC, Sandlie I, Blundell PA, Pleass RJ. Sci Rep. 2015 Apr 27;5:9526. doi: 10.1038/srep09526.
Start Year 2014
 
Description Engineering and Dissecting the Glycosylation Pathway of a Streptococcal Serine-rich Repeat Adhesin 
Organisation University of Alabama at Birmingham
Country United States 
Sector Academic/University 
PI Contribution Mass spectrometric structural analysis of biologically important biomolecules. Intellectual input into experimental design, data interpretation and biological relevance of project outcomes.
Collaborator Contribution Intellectual input into experimental design, data interpretation and biological relevance of project outcomes.
Impact Engineering and Dissecting the Glycosylation Pathway of a Streptococcal Serine-rich Repeat Adhesin. Zhu F, Zhang H, Yang T, Haslam SM, Dell A, Wu H. J Biol Chem. 2016 Dec 30;291(53):27354-27363. doi: 10.1074/jbc.M116.75299.
Start Year 2015
 
Description Enhanced Aromatic Sequons Increase Oligosaccharyltransferase Glycosylation Efficiency and Glycan Homogeneity 
Organisation Scripps Research Institute
Department Department of Chemistry
Country United States 
Sector Charity/Non Profit 
PI Contribution Mass spectrometric structural analysis of biologically important biomolecules. Intellectual input into experimental design, data interpretation and biological relevance of project outcomes.
Collaborator Contribution Intellectual input into experimental design, data interpretation and biological relevance of project outcomes.
Impact Enhanced Aromatic Sequons Increase Oligosaccharyltransferase Glycosylation Efficiency and Glycan Homogeneity. Murray AN, Chen W, Antonopoulos A, Hanson SR, Wiseman RL, Dell A, Haslam SM, Powers DL, Powers ET, Kelly JW. Chem Biol. 2015 Aug 20;22(8):1052-62. doi: 10.1016/j.chembiol.2015.06.017.
Start Year 2014
 
Description Evidence for Differential Glycosylation of Trophoblast Cell Types 
Organisation University of Missouri
Department Division of Reproductive and Perinatal Research
Country United States 
Sector Academic/University 
PI Contribution Mass spectrometric structural analysis of biologically important biomolecules. Intellectual input into experimental design, data interpretation and biological relevance of project outcomes.
Collaborator Contribution Intellectual input into experimental design, data interpretation and biological relevance of project outcomes.
Impact Evidence for Differential Glycosylation of Trophoblast Cell Types. Chen Q, Pang PC, Cohen ME, Longtine MS, Schust DJ, Haslam SM, Blois SM, Dell A, Clark GF. Mol Cell Proteomics. 2016 Jun;15(6):1857-66. doi: 10.1074/mcp.M115.055798.
Start Year 2015
 
Description Global N-linked Glycosylation is Not Significantly Impaired in Myoblasts in Congenital Myasthenic Syndromes Caused by Defective Glutamine-Fructose-6-Phosphate Transaminase 1 (GFPT1) 
Organisation Newcastle University
Department Institute of Genetic Medicine
Country United Kingdom 
Sector Academic/University 
PI Contribution Mass spectrometric structural analysis of biologically important biomolecules. Intellectual input into experimental design, data interpretation and biological relevance of project outcomes.
Collaborator Contribution Intellectual input into experimental design, data interpretation and biological relevance of project outcomes.
Impact Global N-linked Glycosylation is Not Significantly Impaired in Myoblasts in Congenital Myasthenic Syndromes Caused by Defective Glutamine-Fructose-6-Phosphate Transaminase 1 (GFPT1). Chen Q, Müller JS, Pang PC, Laval SH, Haslam SM, Lochmüller H, Dell A. Biomolecules. 2015 Oct 16;5(4):2758-81. doi: 10.3390/biom5042758.
Start Year 2014
 
Description GlyTouCan 1.0--The international glycan structure repository 
Organisation National Institute of Advanced Industrial Science and Technology
Department Glycoscience and Glycotechnology Research Group
Country Japan 
Sector Private 
PI Contribution Mass spectrometric structural analysis of biologically important biomolecules. Intellectual input into experimental design, data interpretation and biological relevance of project outcomes.
Collaborator Contribution Intellectual input into experimental design, data interpretation and biological relevance of project outcomes.
Impact GlyTouCan 1.0--The international glycan structure repository. Aoki-Kinoshita K, Agravat S, Aoki NP, Arpinar S, Cummings RD, Fujita A, Fujita N6, Hart GM, Haslam SM, Kawasaki T, Matsubara M, Moreman KW, Okuda S, Pierce M, Ranzinger R, Shikanai T, Shinmachi D, Solovieva E, Suzuki Y, Tsuchiya S, Yamada I, York WS, Zaia J, Narimatsu H. Nucleic Acids Res. 2016 Jan 4;44(D1):D1237-42. doi: 10.1093/nar/gkv1041.
Start Year 2015
 
Description Glycomic characterization of respiratory tract tissues of ferrets: implications for its use in influenza virus infection studies 
Organisation University of Hong Kong
Department Department of Pathology
Country Hong Kong 
Sector Academic/University 
PI Contribution Mass spectrometric structural analysis of biologically important biomolecules. Intellectual input into experimental design, data interpretation and biological relevance of project outcomes.
Collaborator Contribution Intellectual input into experimental design, data interpretation and biological relevance of project outcomes.
Impact Glycomic characterization of respiratory tract tissues of ferrets: implications for its use in influenza virus infection studies. Jia N, Barclay WS, Roberts K, Yen HL, Chan RW, Lam AK, Air G, Peiris JS, Dell A, Nicholls JM, Haslam SM. J Biol Chem. 2014 Oct 10;289(41):28489-504. doi: 10.1074/jbc.M114.588541.
Start Year 2013
 
Description Glycosphingolipid synthesis inhibition limits osteoclast activation and myeloma bone disease 
Organisation Imperial College London
Country United Kingdom 
Sector Academic/University 
PI Contribution Mass spectrometric structural analysis of biologically important biomolecules. Intellectual input into experimental design, data interpretation and biological relevance of project outcomes.
Collaborator Contribution Intellectual input into experimental design, data interpretation and biological relevance of project outcomes.
Impact Glycosphingolipid synthesis inhibition limits osteoclast activation and myeloma bone disease. Ersek A, Xu K, Antonopoulos A, Butters TD, Santo AE, Vattakuzhi Y, Williams LM, Goudevenou K, Danks L, Freidin A, Spanoudakis E, Parry S, Papaioannou M, Hatjiharissi E, Chaidos A, Alonzi DS, Twigg G, Hu M, Dwek RA, Haslam SM, Roberts I, Dell A, Rahemtulla A, Horwood NJ, Karadimitris A. J Clin Invest. 2015 Jun;125(6):2279-92. doi: 10.1172/JCI59987.
Start Year 2008
 
Description Glycosphingolipids on Human Myeloid Cells Stabilize E-Selectin-Dependent Rolling in the Multistep Leukocyte Adhesion Cascade 
Organisation University at Buffalo
Country United States 
Sector Academic/University 
PI Contribution Mass spectrometric structural analysis of biologically important biomolecules. Intellectual input into experimental design, data interpretation and biological relevance of project outcomes.
Collaborator Contribution Intellectual input into experimental design, data interpretation and biological relevance of project outcomes.
Impact Glycosphingolipids on Human Myeloid Cells Stabilize E-Selectin-Dependent Rolling in the Multistep Leukocyte Adhesion Cascade. Mondal N, Stolfa G, Antonopoulos A, Zhu Y, Wang SS, Buffone A Jr, Atilla-Gokcumen GE, Haslam SM, Dell A, Neelamegham S. Arterioscler Thromb Vasc Biol. 2016 Apr;36(4):718-27. doi: 10.1161/ATVBAHA.115.306748.
Start Year 2015
 
Description Golgi self-correction generates bioequivalent glycans to preserve cellular homeostasis 
Organisation University of California, Irvine
Country United States 
Sector Academic/University 
PI Contribution Mass spectrometric structural analysis of biologically important biomolecules. Intellectual input into experimental design, data interpretation and biological relevance of project outcomes.
Collaborator Contribution Intellectual input into experimental design, data interpretation and biological relevance of project outcomes.
Impact Golgi self-correction generates bioequivalent glycans to preserve cellular homeostasis. Mkhikian H, Mortales CL, Zhou RW, Khachikyan K, Wu G, Haslam SM, Kavarian P, Dell A, Demetriou M. Elife. 2016 Jun 8;5. pii: e14814. doi: 10.7554/eLife.14814.
Start Year 2015
 
Description Gp120 on HIV-1 Virions Lacks O-Linked Carbohydrate 
Organisation Harvard University
Department New England Primate Research Center
Country United States 
Sector Academic/University 
PI Contribution Mass spectrometric structural analysis of biologically important biomolecules. Intellectual input into experimental design, data interpretation and biological relevance of project outcomes.
Collaborator Contribution Intellectual input into experimental design, data interpretation and biological relevance of project outcomes.
Impact Gp120 on HIV-1 Virions Lacks O-Linked Carbohydrate. Stansell E, Panico M, Canis K, Pang PC, Bouché L, Binet D, O'Connor MJ, Chertova E, Bess J, Lifson JD, Haslam SM, Morris HR, Desrosiers RC, Dell A. PLoS One. 2015 Apr 27;10(4):e0124784. doi: 10.1371/journal.pone.0124784.
Start Year 2014
 
Description JAGN1 deficiency causes aberrant myeloid cell homeostasis and congenital neutropenia 
Organisation Ludwig Maximilian University of Munich (LMU Munich)
Department Department of Pediatrics
Country Germany 
Sector Hospitals 
PI Contribution Mass spectrometric structural analysis of biologically important biomolecules. Intellectual input into experimental design, data interpretation and biological relevance of project outcomes.
Collaborator Contribution Intellectual input into experimental design, data interpretation and biological relevance of project outcomes.
Impact JAGN1 deficiency causes aberrant myeloid cell homeostasis and congenital neutropenia. Boztug K, Järvinen PM, Salzer E, Racek T, Mönch S, Garncarz W, Gertz EM, Schäffer AA, Antonopoulos A, Haslam SM, Schieck L, Puchalka J, Diestelhorst J, Appaswamy G, Lescoeur B, Giambruno R, Bigenzahn JW, Elling U, Pfeifer D, Conde CD, Albert MH, Welte K, Brandes G, Sherkat R, van der Werff Ten Bosch J, Rezaei N, Etzioni A, Bellanné-Chantelot C, Superti-Furga G, Penninger JM, Bennett KL, von Blume J, Dell A, Donadieu J, Klein C.
Start Year 2013
 
Description MIRAGE: the minimum information required for a glycomics experiment 
Organisation University of Georgia
Department Complex Carbohydrate Research Center
Country Georgia 
Sector Academic/University 
PI Contribution Mass spectrometric structural analysis of biologically important biomolecules. Intellectual input into experimental design, data interpretation and biological relevance of project outcomes.
Collaborator Contribution Intellectual input into experimental design, data interpretation and biological relevance of project outcomes.
Impact MIRAGE: the minimum information required for a glycomics experiment. York WS, Agravat S, Aoki-Kinoshita KF, McBride R, Campbell MP, Costello CE, Dell A, Feizi T, Haslam SM, Karlsson N, Khoo KH, Kolarich D, Liu Y, Novotny M, Packer NH, Paulson JC, Rapp E, Ranzinger R, Rudd PM, Smith DF, Struwe WB, Tiemeyer M, Wells L, Zaia J, Kettner C. Glycobiology. 2014 May;24(5):402-6. doi: 10.1093/glycob/cwu018.
Start Year 2013
 
Description Mapping the complete glycoproteome of virion-derived HIV-1 gp120 provides insights into broadly neutralizing antibody binding 
Organisation University of Miami
Department Department of Pathology & Laboratory Medicine
Country United States 
Sector Academic/University 
PI Contribution Mass spectrometric structural analysis of biologically important biomolecules. Intellectual input into experimental design, data interpretation and biological relevance of project outcomes.
Collaborator Contribution Intellectual input into experimental design, data interpretation and biological relevance of project outcomes.
Impact Mapping the complete glycoproteome of virion-derived HIV-1 gp120 provides insights into broadly neutralizing antibody binding. Panico M, Bouché L, Binet D, O'Connor MJ, Rahman D, Pang PC, Canis K, North SJ, Desrosiers RC, Chertova E, Keele BF, Bess JW Jr, Lifson JD, Haslam SM, Dell A, Morris HR. Sci Rep. 2016 Sep 8;6:32956. doi: 10.1038/srep32956.
Start Year 2013
 
Description New Helical Binding Domain Mediates a Glycosyltransferase Activity of a Bifunctional Protein 
Organisation University of Alabama at Birmingham
Country United States 
Sector Academic/University 
PI Contribution Mass spectrometric structural analysis of biologically important biomolecules. Intellectual input into experimental design, data interpretation and biological relevance of project outcomes.
Collaborator Contribution Intellectual input into experimental design, data interpretation and biological relevance of project outcomes.
Impact New Helical Binding Domain Mediates a Glycosyltransferase Activity of a Bifunctional Protein. Zhang H, Zhou M, Yang T, Haslam SM, Dell A, Wu H. J Biol Chem. 2016 Oct 14;291(42):22106-22117.
Start Year 2015
 
Description Partial correction of neutrophil dysfunction by oral galactose therapy in glycogen storage disease type Ib 
Organisation University Hospital of Münster
Country Germany 
Sector Hospitals 
PI Contribution Mass spectrometric structural analysis of biologically important biomolecules. Intellectual input into experimental design, data interpretation and biological relevance of project outcomes.
Collaborator Contribution Intellectual input into experimental design, data interpretation and biological relevance of project outcomes.
Impact Partial correction of neutrophil dysfunction by oral galactose therapy in glycogen storage disease type Ib. Letkemann R, Wittkowski H, Antonopoulos A, Podskabi T, Haslam SM, Föll D, Dell A, Marquardt T. Int Immunopharmacol. 2017 Mar;44:216-225. doi: 10.1016/j.intimp.2017.01.020.
Start Year 2016
 
Description Profiling of glycan receptors for minute virus of mice in permissive cell lines towards understanding the mechanism of cell recognition 
Organisation University of Florida
Department Department of Biochemistry and Molecular Biology
Country United States 
Sector Academic/University 
PI Contribution Mass spectrometric structural analysis of biologically important biomolecules. Intellectual input into experimental design, data interpretation and biological relevance of project outcomes.
Collaborator Contribution Intellectual input into experimental design, data interpretation and biological relevance of project outcomes.
Impact Profiling of glycan receptors for minute virus of mice in permissive cell lines towards understanding the mechanism of cell recognition. Halder S, Cotmore S, Heimburg-Molinaro J, Smith DF, Cummings RD, Chen X, Trollope AJ, North SJ, Haslam SM, Dell A, Tattersall P, McKenna R, Agbandje-McKenna M. PLoS One. 2014 Jan 27;9(1):e86909. doi: 10.1371/journal.pone.0086909.
Start Year 2013
 
Description Role of Glycosyltransferases Modifying Type B Flagellin of Emerging Hypervirulent Clostridium difficile Lineages and Their Impact on Motility and Biofilm Formation 
Organisation London School of Hygiene and Tropical Medicine (LSHTM)
Department Department of Pathogen Molecular Biology
Country United Kingdom 
Sector Academic/University 
PI Contribution Mass spectrometric structural analysis of biologically important biomolecules. Intellectual input into experimental design, data interpretation and biological relevance of project outcomes.
Collaborator Contribution Intellectual input into experimental design, data interpretation and biological relevance of project outcomes.
Impact Role of Glycosyltransferases Modifying Type B Flagellin of Emerging Hypervirulent Clostridium difficile Lineages and Their Impact on Motility and Biofilm Formation. Valiente E, Bouché L, Hitchen P, Faulds-Pain A, Songane M, Dawson LF, Donahue E, Stabler RA, Panico M, Morris HR, Bajaj-Elliott M, Logan SM, Dell A, Wren BW. J Biol Chem. 2016 Dec 2;291(49):25450-25461.
Start Year 2015
 
Description ST3Gal-4 is the primary sialyltransferase regulating the synthesis of E-, P-, and L-selectin ligands on human myeloid leukocytes 
Organisation State University of New York
Country United States 
Sector Academic/University 
PI Contribution Mass spectrometric structural analysis of biologically important biomolecules. Intellectual input into experimental design, data interpretation and biological relevance of project outcomes.
Collaborator Contribution Intellectual input into experimental design, data interpretation and biological relevance of project outcomes.
Impact ST3Gal-4 is the primary sialyltransferase regulating the synthesis of E-, P-, and L-selectin ligands on human myeloid leukocytes. Mondal N, Buffone A Jr, Stolfa G, Antonopoulos A, Lau JT, Haslam SM, Dell A, Neelamegham S. Blood. 2015 Jan 22;125(4):687-96. doi: 10.1182/blood-2014-07-588590
Start Year 2014
 
Description Symbol Nomenclature for Graphical Representations of Glycans 
Organisation Washington University in St Louis
Country United States 
Sector Academic/University 
PI Contribution Mass spectrometric structural analysis of biologically important biomolecules. Intellectual input into experimental design, data interpretation and biological relevance of project outcomes.
Collaborator Contribution Intellectual input into experimental design, data interpretation and biological relevance of project outcomes.
Impact Symbol Nomenclature for Graphical Representations of Glycans. Varki A, Cummings RD, Aebi M, Packer NH, Seeberger PH, Esko JD, Stanley P, Hart G, Darvill A, Kinoshita T, Prestegard JJ, Schnaar RL, Freeze HH, Marth JD, Bertozzi CR, Etzler ME, Frank M, Vliegenthart JF, Lütteke T, Perez S, Bolton E, Rudd P, Paulson J, Kanehisa M, Toukach P, Aoki-Kinoshita KF, Dell A, Narimatsu H, York W, Taniguchi N, Kornfeld S. Glycobiology. 2015 Dec;25(12):1323-4. doi: 10.1093/glycob/cwv091.
Start Year 2014
 
Description Systemic blockade of sialylation in mice with a global inhibitor of sialyltransferases 
Organisation Scripps Research Institute
Country United States 
Sector Charity/Non Profit 
PI Contribution Mass spectrometric structural analysis of biologically important biomolecules. Intellectual input into experimental design, data interpretation and biological relevance of project outcomes.
Collaborator Contribution Intellectual input into experimental design, data interpretation and biological relevance of project outcomes.
Impact Systemic blockade of sialylation in mice with a global inhibitor of sialyltransferases. Macauley MS, Arlian BM, Rillahan CD, Pang PC, Bortell N, Marcondes MC, Haslam SM, Dell A, Paulson JC. J Biol Chem. 2014 Dec 19;289(51):35149-58. doi: 10.1074/jbc.M114.606517.
Start Year 2013
 
Description The Cytotoxicity of Elderberry Ribosome-Inactivating Proteins Is Not Solely Determined by Their Protein Translation Inhibition Activity 
Organisation University of Ghent
Department Department Molecular Biotechnology
Country Belgium 
Sector Academic/University 
PI Contribution Mass spectrometric structural analysis of biologically important biomolecules. Intellectual input into experimental design, data interpretation and biological relevance of project outcomes.
Collaborator Contribution Intellectual input into experimental design, data interpretation and biological relevance of project outcomes.
Impact The Cytotoxicity of Elderberry Ribosome-Inactivating Proteins Is Not Solely Determined by Their Protein Translation Inhibition Activity. Shang C, Chen Q, Dell A, Haslam SM, De Vos WH, Van Damme EJ. PLoS One. 2015 Jul 6;10(7):e0132389. doi: 10.1371/journal.pone.0132389.
Start Year 2014
 
Description The Type B Flagellin of Hypervirulent Clostridium difficile Is Modified with Novel Sulfonated Peptidylamido-glycans 
Organisation London School of Hygiene and Tropical Medicine (LSHTM)
Department Department of Pathogen Molecular Biology
Country United Kingdom 
Sector Academic/University 
PI Contribution Mass spectrometric structural analysis of biologically important biomolecules. Intellectual input into experimental design, data interpretation and biological relevance of project outcomes.
Collaborator Contribution Intellectual input into experimental design, data interpretation and biological relevance of project outcomes.
Impact The Type B Flagellin of Hypervirulent Clostridium difficile Is Modified with Novel Sulfonated Peptidylamido-glycans. Bouché L, Panico M, Hitchen P, Binet D, Sastre F, Faulds-Pain A, Valiente E, Vinogradov E, Aubry A, Fulton K, Twine S, Logan SM, Wren BW, Dell A, Morris HR. J Biol Chem. 2016 Dec 2;291(49):25439-25449.
Start Year 2015
 
Description The highly conserved domain of unknown function 1792 has a distinct glycosyltransferase fold 
Organisation University of Alabama at Birmingham
Department Departments of Pediatric Dentistry
Country United States 
Sector Academic/University 
PI Contribution Mass spectrometric structural analysis of biologically important biomolecules. Intellectual input into experimental design, data interpretation and biological relevance of project outcomes.
Collaborator Contribution Intellectual input into experimental design, data interpretation and biological relevance of project outcomes.
Impact The highly conserved domain of unknown function 1792 has a distinct glycosyltransferase fold. Zhang H, Zhu F, Yang T, Ding L, Zhou M, Li J, Haslam SM, Dell A, Erlandsen H, Wu H. Nat Commun. 2014 Jul 15;5:4339. doi: 10.1038/ncomms5339.
Start Year 2013
 
Description The human fetoembryonic defense system hypothesis: Twenty years on. 
Organisation University of Missouri
Department Department of Obstetrics, Gynecology and Women's Health
Country United States 
Sector Hospitals 
PI Contribution Review
Collaborator Contribution Review
Impact The human fetoembryonic defense system hypothesis: Twenty years on. Pang PC, Haslam SM, Dell A, Clark GF. Mol Aspects Med. 2016 Oct;51:71-88. doi: 10.1016/j.mam.2016.06.002.
Start Year 2013
 
Description The minimum information required for a glycomics experiment (MIRAGE) project: improving the standards for reporting glycan microarray-based data 
Organisation Emory University
Country United States 
Sector Academic/University 
PI Contribution Mass spectrometric structural analysis of biologically important biomolecules. Intellectual input into experimental design, data interpretation and biological relevance of project outcomes.
Collaborator Contribution Intellectual input into experimental design, data interpretation and biological relevance of project outcomes.
Impact The minimum information required for a glycomics experiment (MIRAGE) project: improving the standards for reporting glycan microarray-based data. 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 KH, Kolarich D, Novotny MV, 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 DF. Glycobiology. 2016 Nov 22.
Start Year 2015
 
Description The minimum information required for a glycomics experiment (MIRAGE) project: sample preparation guidelines for reliable reporting of glycomics datasets 
Organisation Beilstein Institute
Country Germany 
Sector Charity/Non Profit 
PI Contribution Mass spectrometric structural analysis of biologically important biomolecules. Intellectual input into experimental design, data interpretation and biological relevance of project outcomes.
Collaborator Contribution Intellectual input into experimental design, data interpretation and biological relevance of project outcomes.
Impact The minimum information required for a glycomics experiment (MIRAGE) project: sample preparation guidelines for reliable reporting of glycomics datasets. 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 C.
Start Year 2015
 
Description The use of surface immobilization of P-selectin glycoprotein ligand-1 on mesenchymal stem cells to facilitate selectin mediated cell tethering and rolling 
Organisation University at Buffalo
Department Department of Chemical and Biological Engineering
Country United States 
Sector Academic/University 
PI Contribution Mass spectrometric structural analysis of biologically important biomolecules. Intellectual input into experimental design, data interpretation and biological relevance of project outcomes.
Collaborator Contribution Intellectual input into experimental design, data interpretation and biological relevance of project outcomes.
Impact The use of surface immobilization of P-selectin glycoprotein ligand-1 on mesenchymal stem cells to facilitate selectin mediated cell tethering and rolling. Lo CY, Antonopoulos A, Dell A, Haslam SM, Lee T, Neelamegham S. Biomaterials. 2013 Nov;34(33):8213-22. doi: 10.1016/j.biomaterials.2013.07.033.
Start Year 2013
 
Description The zebrafish galectins Drgal1-L2 and Drgal3-L1 bind in vitro to the infectious hematopoietic necrosis virus (IHNV) glycoprotein and reduce viral adhesion to fish epithelial cells 
Organisation University of Maryland, Baltimore
PI Contribution Mass spectrometric structural analysis of biologically important biomolecules. Intellectual input into experimental design, data interpretation and biological relevance of project outcomes.
Collaborator Contribution Intellectual input into experimental design, data interpretation and biological relevance of project outcomes.
Impact The zebrafish galectins Drgal1-L2 and Drgal3-L1 bind in vitro to the infectious hematopoietic necrosis virus (IHNV) glycoprotein and reduce viral adhesion to fish epithelial cells. Nita-Lazar M, Mancini J, Feng C, González-Montalbán N, Ravindran C, Jackson S, de las Heras-Sánchez A, Giomarelli B, Ahmed H, Haslam SM, Wu G, Dell A, Ammayappan A, Vakharia VN, Vasta GR. Dev Comp Immunol. 2016 Feb;55:241-52. doi: 10.1016/j.dci.2015.09.007.
Start Year 2015
 
Description Towards controlling the glycoform: a model framework linking extracellular metabolites to antibody glycosylation 
Organisation Imperial College London
Department Centre for Process Systems Engineering
Country United Kingdom 
Sector Academic/University 
PI Contribution Mass spectrometric structural analysis of biologically important biomolecules. Intellectual input into experimental design, data interpretation and biological relevance of project outcomes.
Collaborator Contribution Intellectual input into experimental design, data interpretation and biological relevance of project outcomes.
Impact Towards controlling the glycoform: a model framework linking extracellular metabolites to antibody glycosylation. Jedrzejewski PM, del Val IJ, Constantinou A, Dell A, Haslam SM, Polizzi KM, Kontoravdi C. Int J Mol Sci. 2014 Mar 14;15(3):4492-522. doi: 10.3390/ijms15034492.
Start Year 2013
 
Description Unique, polyfucosylated glycan-receptor interactions are essential for regeneration of Hydra magnipapillata 
Organisation Indian Institute of Science, Bangalore
Department Institute for Stem Cell Biology and Regenerative Medicine
PI Contribution Mass spectrometric structural analysis of biologically important biomolecules. Intellectual input into experimental design, data interpretation and biological relevance of project outcomes.
Collaborator Contribution Intellectual input into experimental design, data interpretation and biological relevance of project outcomes.
Impact Unique, polyfucosylated glycan-receptor interactions are essential for regeneration of Hydra magnipapillata. Sahadevan S, Antonopoulos A, Haslam SM, Dell A, Ramaswamy S, Babu P.
Start Year 2013
 
Description XBP1s Links the Unfolded Protein Response to the Molecular Architecture of Mature N-Glycans 
Organisation Massachusetts Institute of Technology
Department Department of Chemistry
Country United States 
Sector Academic/University 
PI Contribution Mass spectrometric structural analysis of biologically important biomolecules. Intellectual input into experimental design, data interpretation and biological relevance of project outcomes.
Collaborator Contribution Intellectual input into experimental design, data interpretation and biological relevance of project outcomes.
Impact XBP1s Links the Unfolded Protein Response to the Molecular Architecture of Mature N-Glycans. Dewal MB, DiChiara AS, Antonopoulos A, Taylor RJ, Harmon CJ, Haslam SM, Dell A, Shoulders MD. Chem Biol. 2015 Oct 22;22(10):1301-12. doi: 10.1016/j.chembiol.2015.09.006.
Start Year 2014
 
Description Multiple school visits and open days 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Schools
Results and Impact Multiple visits to state schools under the Speakers for Schools scheme giving talks to groups of 50-100 pupils. Open days at Imperial College involving over a hundred students, teachers and parents.
Year(s) Of Engagement Activity 2013,2014,2015,2016,2017