Details of Grant 

EPSRC Reference:	EP/P00573X/1
Title:	Integrated workflows for glycan analysis: tagging strategies to facilitate structural and functional characterisation of carbohydrates
Principal Investigator:	Allman, Dr S
Other Investigators:
Researcher Co-Investigators:
Project Partners:
Department:	Faculty of Sci, Tech, Eng & Maths (STEM)
Organisation:	The Open University
Scheme:	First Grant - Revised 2009
Starts:	01 December 2016	Ends:	31 January 2018	Value (£):	100,802
EPSRC Research Topic Classifications:	Carbohydrate Chemistry
EPSRC Industrial Sector Classifications:	Pharmaceuticals and Biotechnology
Related Grants:
Panel History:	Panel Date Panel Name Outcome 21 Jul 2016 EPSRC Physical Sciences Chemistry - July 2016 Announced
Summary on Grant Application Form
Proteins and other important biological molecules such as lipids are often highly decorated with complex chains of carbohydrates. These carbohydrates are involved in many processes, such as cell-cell adhesion and the recognition of pathogens. The types of carbohydrate structures involved in these interactions, however, are often not easily accessible in quantity by standard synthetic routes. This is largely due to their structural complexity and their diversity. In addition, the analysis of these complex and diverse sugars species itself poses many analytical challenges and is often also additionally hampered by the lack of available material. Although chemical synthesis of these sugars is challenging, large carbohydrate structures can be isolated directly from biological molecules and they can be tagged with a fluorescent label to aid their separation. Such technology is exploited commercially in the analysis of biopharmaceuticals, which (as of 2014) made up eight of the ten top selling drugs in Europe. An understanding of the sugars decorating the surface of such therapeutics is an important aspect of quality control, as changes in the sugars displayed on the surface can affect the storage stability, the efficacy and the safety of biologic drugs. Despite the use of this technique in the field of analysis, the labelling strategies commonly employed in this process result in the isolated carbohydrates being of little use for downstream applications and they are routinely discarded. The isolation of sufficient unlabelled material for use in biological assays often requires repeated "blind preparation" where unlabelled material is isolated from a complex mixture of sugars cleaved from the surface of a protein, and a sample of this isolate then labelled and checked for fidelity and purity. Such approaches to isolating carbohydrates require comparatively large quantities of starting material and multiple time-consuming post-processing steps. This project describes the preparation of an alternative fluorescent label exhibiting comparable properties in the separation system, whilst bearing additional functionality which can be exploited to facilitate downstream uses directly. It is the intention that this label will allow for labelled sugars isolated by procedures applied in industrial carbohydrate analysis to be utilised in the production of synthetic glycolipids. These synthetic glycolipids will be layered onto a surface to create artificial cell membranes and also inserted into droplets to mimic whole cells. Using these types of methods to present sugars, we can create systems where the sugars are displayed on a surface in such a way that they mimic the correct orientation, closely modelling how they would be displayed in a natural system. By using different combinations of synthetic glycolipids bearing different fluorescent labels and carrying different defined carbohydrates, it is envisaged that these artificial membrane can be used to investigate how proteins and pathogenic species bind to the sugars displayed on the cell surface. Creating artificial membranes in this way will allow us to investigate not only how different carbohydrates bind to protein partners, but also how combinations of glycolipids bearing different sugars are recruited by pathogens. It will allow us to investigate how such species arrange themselves to maximise binding efficiency when these recognition events take place. A deeper understanding of the nature of these events and how these molecules behave and interact can provide important insights into biological processes, and have the potential to inform the development of diagnostic tools and novel therapeutics. It is also hoped that the same tagged sugars can be made available to the wider scientific community to provide access to hitherto difficult to obtain reagents which can be used directly in a variety of different assays, analytical techniques and synthetic applications.
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