Chemo-enzymatic Production of Specialty Glycans
Lead Research Organisation:
University of Warwick
Department Name: Chemistry
Abstract
Abstracts are not currently available in GtR for all funded research. This is normally because the abstract was not required at the time of proposal submission, but may be because it included sensitive information such as personal details.
Technical Summary
The vision of the project centres around the translation of traditional and novel methodologies to develop sustainable and versatile platforms for the industrial production of glycans on scale. We will demonstrate the technology by targeting a set of novel glycan materials that are anticipated to have significant transformational potential in human health and disease in diagnostics and glycoengineering applications. This project requires an integrated approach featuring: 1) synthetic chemistry (unnatural building blocks) 2) biocatalysis (enzymatic synthesis of larger glycans) 3) showcasing glycan potential in diagnostics (glycoarray based platforms). The significant anticipated progression of both biocatalysis and glycoarray technologies will reduce commercialisation barriers both in terms of commercial glycan production and 'first in the market' glycan array companies.
Planned Impact
As described in the submission of the PI
Publications
Baker AN
(2022)
End-Functionalized Poly(vinylpyrrolidone) for Ligand Display in Lateral Flow Device Test Lines.
in ACS polymers Au
Baker AN
(2021)
Glycan-Based Flow-Through Device for the Detection of SARS-COV-2.
in ACS sensors
Baker AN
(2022)
Lateral Flow Glyco-Assays for the Rapid and Low-Cost Detection of Lectins-Polymeric Linkers and Particle Engineering Are Essential for Selectivity and Performance.
in Advanced healthcare materials
Georgiou PG
(2022)
Plasmonic Detection of SARS-CoV-2 Spike Protein with Polymer-Stabilized Glycosylated Gold Nanorods.
in ACS macro letters
Georgiou PG
(2020)
"Tuning aggregative versus non-aggregative lectin binding with glycosylated nanoparticles by the nature of the polymer ligand".
in Journal of materials chemistry. B
Hollingsworth K
(2023)
A 'glyco-fluorine' code revealing differential recognition by glycan binding partners
Laezza A
(2020)
Protecting Group Free Synthesis of Glyconanoparticles Using Amino-Oxy-Terminated Polymer Ligands.
in Bioconjugate chemistry
Richards SJ
(2018)
Photochemical "In-Air" Combinatorial Discovery of Antimicrobial Co-polymers.
in Chemistry (Weinheim an der Bergstrasse, Germany)
Richards SJ
(2020)
Introducing affinity and selectivity into galectin-targeting nanoparticles with fluorinated glycan ligands.
in Chemical science
Richards SJ
(2021)
Toward Glycomaterials with Selectivity as Well as Affinity.
in JACS Au
| Description | A key aim of this award (the UoW component, as this was split into several sub-grants as part of the award and only UoW is reported here) was to integrate fluorinated glycans, prepared by other partners into a nano-biosensing platform.Our platform uses gold nanoparticles which can generate signal (either colour change or coupled to other analytical techniques) allowing us to rapidly determine if a glycan (sugar) binds a protein partner. This was significant as our technology was suitable for small numbers of glycans (e.g. 5-10 unlike established array techniques which are most effecient with 10's of glycans. Gold particles also form the core of e.g. lateral flow assays (the red line) and hence are candidates for future diagnostics. We first demonstrated the potential of this system by interrogating how influenza proteins can bind glycans, which is a key step in their pathogenic cycle. We then took this further to show how the fluorinated glycans could introduce selectivity against a panel of galectins - important proteins in humans relating to cancer progress (amongst others) - which could not be achieved with 'native' glycans. This shows that either single glycan sensors, or 'pattern recognition' sensors could be developed in the future, using unnatural glycans. |
| Exploitation Route | Inspired by this (and discussed in the impact section) we are now developing glycan-based diagnostics with an industry partner. |
| Sectors | Chemicals,Healthcare,Pharmaceuticals and Medical Biotechnology |
| Description | The skills techniques and trained researcher (Dr Richards) engaged with Iceni Diagnostics (now Iceni Glycosciences) to address questions around COVID-19. Specifically we investigated how COVID binds glycans, using the platforms developed in the original grant. This led to a patent filing, and BBSRC IAA funding. From this we developed prototype COVID-19 lateral-flow/flow-through devices, replacing the need for antibodies with glycans. This is being taken forward by both partners. Further BBSRC IAA funding was used to allow us to explore how the materials we have been developing can be used in the food and biotechnology sector, working with industrial partners. |
| Sector | Healthcare,Pharmaceuticals and Medical Biotechnology |
| Impact Types | Economic |
| Description | BBSRC IAA University of Warwick |
| Amount | £300,000 (GBP) |
| Funding ID | BB/S506783/1 |
| Organisation | Biotechnology and Biological Sciences Research Council (BBSRC) |
| Sector | Public |
| Country | United Kingdom |
| Start | 03/2018 |
| End | 03/2022 |
| Description | EU ITN/MCS Network |
| Amount | € 4,157,229 (EUR) |
| Funding ID | 814236 |
| Organisation | Marie Sklodowska-Curie Actions |
| Sector | Charity/Non Profit |
| Country | Global |
| Start | 09/2018 |
| End | 10/2022 |
| Description | Summer Studentship |
| Amount | £2,500 (GBP) |
| Organisation | IBCarb |
| Sector | Charity/Non Profit |
| Country | United Kingdom |
| Start | 06/2016 |
| End | 09/2016 |
| Description | Travel Grant for Early Career Chemists to attend International Carbohydrate Symposium in New Orleans USA (SJR) |
| Amount | £800 (GBP) |
| Organisation | Royal Society of Chemistry |
| Sector | Charity/Non Profit |
| Country | United Kingdom |
| Start | 07/2016 |
| End | 07/2016 |
| Description | University of Warwick UKRI Innovation Fellowships: BBSRC Flexible Talent Mobility Accounts |
| Amount | £90,000 (GBP) |
| Funding ID | BB/R506588/1 |
| Organisation | Biotechnology and Biological Sciences Research Council (BBSRC) |
| Sector | Public |
| Country | United Kingdom |
| Start | 11/2017 |
| End | 03/2019 |
| Description | Open day |
| Form Of Engagement Activity | Participation in an open day or visit at my research institution |
| Part Of Official Scheme? | No |
| Geographic Reach | National |
| Primary Audience | Schools |
| Results and Impact | Open day tours introducing large numbers of per-university students to our research and facilities. In particular we discussed importance of our research in context of antimicrobial resistance and also in tissue/organ transportation. This sparked conversations with students and their parents |
| Year(s) Of Engagement Activity | 2017 |
| Description | Open day for prospective students |
| Form Of Engagement Activity | Participation in an open day or visit at my research institution |
| Part Of Official Scheme? | No |
| Geographic Reach | National |
| Primary Audience | Schools |
| Results and Impact | Students visiting the University open days. |
| Year(s) Of Engagement Activity | 2018 |
| Description | STEM Ambassador |
| Form Of Engagement Activity | Participation in an open day or visit at my research institution |
| Part Of Official Scheme? | No |
| Geographic Reach | Regional |
| Primary Audience | Schools |
| Results and Impact | Outreach activities aimed at primary and secondary school level students. |
| Year(s) Of Engagement Activity | 2016 |
| URL | http://www.stemnet.org.uk/ambassadors/ |
| Description | Talk at ACS National Meeting |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Postgraduate students |
| Results and Impact | Talk at ACS National Meeting on bioconjugation methods |
| Year(s) Of Engagement Activity | 2019 |
| Description | Talk at Monash University |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | Local |
| Primary Audience | Postgraduate students |
| Results and Impact | talk at Monash university to postgraduate researchers. |
| Year(s) Of Engagement Activity | 2017 |
| Description | Talk at Sheffield University |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | Regional |
| Primary Audience | Postgraduate students |
| Results and Impact | Talk at University of Sheffield to their CDT in polymers and colloids |
| Year(s) Of Engagement Activity | 2018 |
| Description | Think Science A-level conference |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | Regional |
| Primary Audience | Schools |
| Results and Impact | Think Science A-Level Conference. Up to 10 local Sixth-form colleges come for a day to Warwick to hear about latest research. I gave a 30 minute invited lecture and then some one to one meetings on our research |
| Year(s) Of Engagement Activity | 2016 |
| Description | invited talk at University of Santiago, Spain |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | Regional |
| Primary Audience | Postgraduate students |
| Results and Impact | invited lecture to show latest research results |
| Year(s) Of Engagement Activity | 2019 |