Chemo-enzymatic Production of Specialty Glycans

Lead Research Organisation: University of Warwick
Department Name: Chemistry

Abstract

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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

10 25 50
 
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.
First Year Of Impact 2020
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 08/2018 
End 10/2022
 
Description Summer Studentship
Amount £2,500 (GBP)
Organisation IBCarb 
Sector Charity/Non Profit
Country United Kingdom
Start 05/2016 
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 06/2016 
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