European Glycoinitiatives Sabine L Flitsch School of Chemistry

European Glyco-initiatives Sabine L. Flitsch School of Chemistry & Manchester Institute of Biotechnology, University of Manchester, UK PL 11 Euro. Carb XX Leiden , NL| 4 July 2019

Roadmaps in Glycoscience Transforming Glycoscience: A Roadmap for the Future (2012) (NAP. edu/10766) The committee recommends that 1. the development of transformative methods for the facile synthesis of carbohydrates and glycoconjugates be a high priority … 2. the development of transformative tools for detection, imaging, separation, and high-resolution structure determination of carbohydrate structures and complex mixtures be a high priority …. 3. the development of transformative capabilities for perturbing carbohydrate and glycoconjugate structure, recognition, metabolism, and biosynthesis be a high priority …. 4. robust, validated informatics tools be developed in order to enable accurate carbohydrate and glycoconjugate structural prediction, computational modeling, and data mining. … 5. a long-term-funded, stable, integrated, centralized database, including mammalian, plant, and microbial carbohydrates and glycoconjugates, be established as a collaborative effort by all stakeholders…

Roadmaps in Glycoscience The publication output of European R&D glycoscientists is the highest in the world. The size of the circles represents the relative proportion of glycoscience papers published. The 25 top performing countries are depicted. Roadmap published Jan 2015

Roadmaps in Glycoscience Updated European Roadmap due in 2020

Metrology of Carbohydrates for Enabling European Bio. Industries Sabine Flitsch, MIB, University of Manchester, UK https: //carbomet. eu/

Overview of the project • Coordination & Support Action (CSA) funded under Horizon 2020 FET-OPEN • Started 1 st January 2017, 48 months • Budget ~€ 0. 5 M • Focus: Future metrology & analytical science needs concerning carbohydrates & glycoconjugates Background initiatives: • European Glycoscience Forum 2010 – 2014 • EGSF ‘Future of European Glycoscience’ workshop, Mar ‘ 14 • IBCarb (UK) 2014 – 2019 https: //carbomet. eu/ Roadmap published Jan 2015

Project History Scoping workshop: ‘Metrology of Carbohydrates’ workshop, Brussels, February 2016 to focus on the metrology of carbohydrates and glycoconjugates Objectives: To build on ‘A roadmap for Glycoscience in Europe’ and plan next steps for engaging with EU policy makers to get glycoscience onto the Horizon 2020 (and next Framework Horizon Europe) agenda. Who: 57 delegates: from industry (>30) and academia from across Europe Industry representatives: BASF (DE), Bio-Shape Ltd (GB), Covance Laboratories (GB), Dextra UK, DSM (NL), Elicityl (FR), Fermentalg (FR), Friesland Campina (NL), Glycomix Ltd (GB), Glyco. Se. Lect Ltd (IE), GSK Vaccines (IT), Inbiose (BE), Intellihep (GB), LGC (GB), Ludger Ltd (GB), Med. Immune (GB), Nestec (CH), Polymaris Technology (FR), Prozomix (GB), Sanofi (FR), Td. B Consultancy (SE), UCB (GB), Unilever (GB), and Waters Corporation (GB). Outcome: Successful application for ’Carbo. Met’ Coordination & Support Action, under https: //carbomet. eu/ FET OPEN, Horizon 2020, to maintain momentum.

Aims and Objectives Carbo. Met will facilitate engagement between key players and stakeholders to ensure full engagement of the glycoscience community across Europe. Activities: • Website & online surveys • Meetings & workshops including training workshops in advanced technologies • Policy briefings & white papers Bio. Industry Sector (BIS) Enabling Technology Area (ETA) Biopharmaceuticals including vaccines, antimicrobials, antibodies and hormones Analytics & Measurements Diagnosis of disease for development of Precision Medicines Healthy Living: Food & Personal Care Carbo. Met Stakeholder Input Manufacturers Synthesis of Standards Bioinformatics & Databases Carbohydrates as Sustainable Materials Innovation Centres Research Groups Consumers Patients Social Scientists

Carbo. Met so far. . 328 Number of stakeholders engaged from Industry and Academia 34 57 Centre of Expertise in Carbohydrate Research 25 Centres in Measurements and Analytics Database and Bioinformatics tool identified 29 Centres in Carbohydrate Synthesis 7 2 Centres in Bioinformatics and Databases Number of workshops held around Europe with participants from Industry and Academia https: //carbomet. eu/ 32 Number of engagements with policy makers, European-wide glycoinitiatives and industrial partners in the healthcare and chemical sector.

Carbohydrate-based vaccines targeting antimicrobial resistance The improvident use of antibiotics in clinical settings and animal husbandry has been a major cause for the rapidly developing problem of antimicrobial resistance (AMR), which is posing an increasing healthcare challenge for both developed and developing countries. 10 million Number of estimated deaths from AMR. That’s more than cancer! Improved and robust Vaccine Workshop held in 2018 with 32 delegates from industry and academia to identify 7 key areas for development. Advance sequencing Accurate Monitoring of Polysaccharide production Metrology / Informatics Regulations, IP Data integration and ISO standards Optimising Glycoconjugate / adjuvant design New business models https: //carbomet. eu/

Carbohydrates in promoting gut microbiota functions https: //carbomet. eu/ The gut microbiota has in recent years undergone intense research on how the microbiome and particularly the imbalance of the microbial populations (‘dysbiosis’) are associated with a number of inflammation and infection conditions. Workshop held in 2018 with 38 delegates from industry and academia to identify 5 challenges to address. Cited by the European Association of Bio. Industries (Europa. Bio). New metrology and analytics Elucidating relationship Between microbiota and Human gut Data management and integration Biotechnological production of carbohydrates New strategies to promote healthy diet

Sustainable materials of the future The development of bio-inspired sustainable materials from carbohydrates has steadily gained interest from the chemical industry as a strategy to produce new materials with unique properties from waste resources. Workshop held in 2019 with 27 delegates from industry and academia to identify 5 challenges to address. Packaging, films and displays Textiles Prosthetics and regenerative medicine Food ingredients Cognitive processing to predict structure, function https: //carbomet. eu/ and relationship

Funding opportunities Horizon health 2020 calls: Same priority areas as for 2018 -2019 1) Personalised Medicine 2) Innovative health and care industry 3) Infectious diseases and improving global health 4) Innovative health and care systems - Integration of care 5) Decoding the role of the overall environment for health and well-being Indicative budget • EUR 490 million IMI calls: Priority areas for 2020 1) Neurodegeneration and other neuroscience priorities 2) Immunology 3) Infection control including vaccines – AMR accelerator platform 4) Translational safety 5) Big data, digital health, clinical trials and regulatory research 6) Facilitating the translation of advanced therapies to patients in Europe Indicative budget • TBC

Funding opportunities aligned with Carbo. Met initiatives AMR accelerator platform Accelerate scientific discoveries in antimicrobial resistance (AMR) and to progress a pipeline of potential therapeutic, biologic and preventive medicines & procedures, e. g. diagnostics, to manage patients and/or populations with resistant bacterial infections in Europe and across the globe. Links: https: //www. imi. europa. eu/apply-funding/future-topics From functional ecosystems to healthy food Calls include: SFS-11 -2018 -2019: Anti-microbials and animal production – Alternative treatments other than vaccine such as modulation of host immunity and/or of microbial flora, feed additives or novel molecules. Link: https: //ec. europa. eu/programmes/horizon 2020/sites/horizon 2020/files/food_h 2 020_wp_2018 -2020_draft. pdf Bio-based industries calls and H 2020 NMBP Topics include: Develop bio-based materials for high-volume consumer products and smart plastic materials with recycling properties. Links: https: //ec. europa. eu/programmes/horizon 2020/sites/horizon 2020/files/h 2020 leit-nmbp-2018 -2020_pre-publication. pdf

How Carbo. Met is helping the European glycoscience community Engaging with policymakers and multiple stakeholders from industry and academia to create policy papers and a technology roadmap to accelerate innovation and development in the scientific community. Carbo. Met is conducting a survey to collect responses from a range of stakeholders across the four BIS. The responses will be used towards the publication of policy papers to be disseminated to national and international academic and industry associations. Please go the Carbo. Met website (carbomet. eu) > About > Link to survey can be found in the text.

How to keep in touch with Carbo. Met Please join our Linked. In group and/or sign up to our newsletter for updates on news, policy papers and other Carbo. Met initiatives. Links and instructions can be found on our website. Project coordinators: Sabine Flitsch & Syed Ahmed, MIB, University of Manchester, UK Working group: Daniel Spencer (Ludger Limited, GB) Isabelle Compagnon (Université de Lyon Claude Bernard, FR) Paula Domann (LGC Limited, GB) Anne Imberty (CERMAV, CNRS, FR) Lokesh Joshi (National University of Ireland - Galway, IE) Frederique Lisacek (Swiss Institute of Bioinformatics, CH) Serge Perez (CNRS, FR) Peter Seeberger (Max Planck Institute of Colloids and Interfaces, DE) email: projectmanager@carbomet. eu Twitter: @Carbo. Met_EU https: //carbomet. eu/

Roadmaps in Glycoscience Transforming Glycoscience: A Roadmap for the Future (2012) (NAP. edu/10766) The committee recommends that 1. the development of transformative methods for the facile synthesis of carbohydrates and glycoconjugates be a high priority … 2. the development of transformative tools for detection, imaging, separation, and high-resolution structure determination of carbohydrate structures and complex mixtures be a high priority …. 3. the development of transformative capabilities for perturbing carbohydrate and glycoconjugate structure, recognition, metabolism, and biosynthesis be a high priority …. 4. robust, validated informatics tools be developed in order to enable accurate carbohydrate and glycoconjugate structural prediction, computational modeling, and data mining. … 5. a long-term-funded, stable, integrated, centralized database, including mammalian, plant, and microbial carbohydrates and glycoconjugates, be established as a collaborative effort by all stakeholders…

Analytical Methods

Current Carbohydrate Sequencing methods Gray et al, under review

NMR analysis of Glycans Fontana, C. ; Kovacs, H. ; Widmalm, G. , Journal of Biomolecular NMR 2014, 59 (2), 95 -110.

Glycomic analysis of N-glycans α 3 α 3 α 6 a) 4 4 α 3 α 6 4 2 2 α 3 4 2 2 4 4 4 α 6 α 3 4 α α α 6 3 2 4 4 2 6 α 3 4 4 4 α α 3 6 2 2 4 4 α 6 α α α 3 4 4 6 3 6 α 4 4 4 α α α 2 2 4 α α 3 6 4 4 4 2 4 4 α 6 2 α α 3 6 α 3 α 4 α α 4 4 2 6 4 2 2 α 3 α α 3 4 4 2 2 4 2 3 6 4 2 2 6 4 α α 3 4 6 α α α 3 6 6 α 4 4 6 α 3 α 4 4 2 2 4 6 α 4 4 6 α α 6 b) Rudd et al. , Scientific Reports 2018, 8.

MS Ion Mobility Spectrometry Both et al. , Nat. Chem. 2014, 6, 65. |Schindler et al. , Nat. Comm. 2017, 8 (1), 973|Gray et al. , Anal. Chem. 2017, ref 52, 4381. 89 (8), 4540 | Gray et al BBA 2016, 1860 (8), 1688 -1709 |Hinnenburg et al. , Chem. Commun. 2016,

MS + Infra. Red Khanal N. et al. Anal. Chem. 2017, 89, 7601 -7606| Schindler et al. , Nat. Comm. 2017, 8 (1), 973

Fragment-based sequence analysis of carbohydrates MS MS MS Both et al. , Nat. Chem. 2014, 6, 65. Schindler et al. , Nat. Comm. 2017, 8 (1), 973 Gray et al. , Anal. Chem. 2017, 89 (8), 4540 -4549 Gray et al BBA 2016, 1860 (8), 1688 -1709 Hinnenburg et al. , Chem. Commun. 2016, 52, 4381.

Fragment-based sequence analysis of carbohydrates NMR Synthesis of standards Both et al. , Nat. Chem. 2014, 6, 65. Schindler et al. , Nat. Comm. 2017, 8 (1), 973 Gray et al. , Anal. Chem. 2017, 89 (8), 4540 -4549 Gray et al BBA 2016, 1860 (8), 1688 -1709 Hinnenburg et al. , Chem. Commun. 2016, 52, 4381.

How to keep in touch with Carbo. Met Please join our Linked. In group and/or sign up to our newsletter for updates on news, policy papers and other Carbo. Met initiatives. Links and instructions can be found on our website. Project coordinators: Sabine Flitsch & Syed Ahmed, MIB, University of Manchester, UK Working group: Daniel Spencer (Ludger Limited, GB) Isabelle Compagnon (Université de Lyon Claude Bernard, FR) Paula Domann (LGC Limited, GB) Anne Imberty (CERMAV, CNRS, FR) Lokesh Joshi (National University of Ireland - Galway, IE) Frederique Lisacek (Swiss Institute of Bioinformatics, CH) Serge Perez (CNRS, FR) Peter Seeberger (Max Planck Institute of Colloids and Interfaces, DE) email: projectmanager@carbomet. eu Twitter: @Carbo. Met_EU https: //carbomet. eu/