Chemo-enzymatic Production of Specialty Glycans

Lead Research Organisation: University of Manchester
Department Name: Chemistry

Abstract

This project will investigate the enzymatic glycosylation of modified carbohydrate monosaccharides to achieve larger, biologically relevant glycan structures. This will be achieved by extensive screening of glycosyltransferase enzymes (enzymes that catalyse the addition of a new monosaccharide to a growing sugar 'acceptor'), that are able to use modified sugars as the 'acceptor', but also as 'donor'.
The biological relevance of the synthesised new type of glycan structures will be validated by investigating their binding profile to a range of proteins that are known to be of relevance in the health sciences, with the immediate aim to develop new diagnostics applications. However, depending on the array results, further applications in other areas in the health sciences are envisaged.

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
 
Description Too early to comment, the project has only been running since October 2015 and the UoM PDRA does not commence work until June 2016
Exploitation Route too early to comment
Sectors Healthcare,Manufacturing, including Industrial Biotechology,Pharmaceuticals and Medical Biotechnology

 
Description BBSRC The Great British Biosciences Festival, 14-16th November 2014 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact Professor Sabine Flitsch was successful in her bid to host "The Complex Life of Sugars" at BBSRC The Great British Biosciences Festival, 14-16th November 2014, London. The exhibition was visited by over 6,500 visitors including people from the following categories: students, teachers, public, scientists, media, potential donors/key decision makers and celebrities. One of the main exhibition activities was focused on cell surface sugars and visitors were encouraged to build a cell surface sugar and explore its interaction with cell invaders both on a cell surface and also a gold glycan array. For more contents please visit our blog http://sugar-complexity.tumblr.com/ and twitter feed @sugarcomplexity.
Year(s) Of Engagement Activity 2014
 
Description Gateways Widening Participation Event 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Schools
Results and Impact The activities included glycan building through arts-and-crafts, enzymatic glucose testing and a luminol demonstration, with all activities linked to the science of blood - something familiar to all the students attending. This helped high-school students to link classroom science to the real world and explore different options as a career in science. It also integrated current research topics form this project and the wider research institute.
Year(s) Of Engagement Activity 2019
 
Description Manchester Institute of Biotechnology Open Day, 8th November 2013 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Schools
Results and Impact The MIB Open Day was specifically aimed at A-Level students nationally. The day focused on hands-on experiments and lectures to promote working at the interface between chemistry and biology to solve problems with a biological 'green' solution and encourage science students to pick applied science subjects. The feedback was very positive with pupils reporting that they now realized there were a lot more options for further study and jobs than they previously knew about.
Year(s) Of Engagement Activity 2013
 
Description New Scientist Live (EXCEL London) 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact 22,476 visitors, 81 pieces of news coverage, 208 journalists attended and reached 623 million people - we had visitors following up asking for resources which we have made into an activity pack for schools.
Year(s) Of Engagement Activity 2016
URL https://live.newscientist.com/
 
Description Royal Society Satellite Science Exhibition (Manchester Museum of Science and Industry) 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Public/other audiences
Results and Impact Family friendly hands on exhibition "The Complex Life of Sugars" showcasing stands from previous Royal Society Summer Science Exhibitions, estimated attendance at the stand, over 200 people per day for 5 days
Year(s) Of Engagement Activity 2016
URL https://royalsociety.org/science-events-and-lectures/science-exhibition-manchester/
 
Description Science Spectacular, Manchester Museum 2nd November 2014 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Public/other audiences
Results and Impact The Science Spectacular is aimed at families to promote sciences as fun and useful. The feedback from individuals questioned were all positive, reporting changes in their opinions and behaviour and more pupils expressing an interest in studying science further.
Year(s) Of Engagement Activity 2014
 
Description ScienceX (The Trafford Centre Manchester) 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Public/other audiences
Results and Impact ScienceX was part of Manchester City of Science/ESOF. We took hands on experiments including sugar building and smelling compounds in cola which can be made using biotechnology. It reached passers-by at The Trafford Centre and an audience that would not normally attend science exhibitions. The participants said that they did not like science at school and then really enjoyed the activities and discussions. It gave lots of people more confidence in their scientific abilities.
Year(s) Of Engagement Activity 2016
 
Description The Science Spectacular, Manchester Museum, 2nd November 2013 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Public/other audiences
Results and Impact The Royal Society Summer Science Exhibition proved so popular that we were asked to be part of The Science Spectacular, 2nd November 2013 at The Manchester Museum http://www.manchestersciencefestival.com/whatson/science-spectacular. The Science Spectacular was aimed primarily at young children and families to encourage children to enjoy science. The feedback from parents was very positive.
Year(s) Of Engagement Activity 2013
URL http://www.manchestersciencefestival.com/whatson/science-spectacular