Research & Development for Medical Glycomics



Ludger mass spectrometry analysis




Ludger's Medical Glycomics Programmes have been established to study changes in glycosylation in different body states. These include inflammation, cancers, diabetes and CVD.

This area of study originated in the work published in Nature by Parekh et al in 1985 entitled 'Association of Rheumatoid Arthritis and Primary Osteoarthritis with Changes in the Glycosylation Pattern of Total Serum IgG' : Nature 316, 452-457 (01 August 1985) and has led to a strong initiative to explore the relevance of glycomics in Precision Medicine.

The glycomics data generated from our studies is being used for the following:

  • To identify new biomarkers
  • For patient stratification in specific diseases

Core capabilities and expertise:

  • High throughput sample preparation and analysis utilising kits and glycan standards developed and manufactured at Ludger
  • Methods have been adapted for a liquid handling robot
  • Tens of thousands of samples have been processed and analysed to date
  • Ability to process a wide range of glycoproteins, including biopharmaceutical samples, cell lines, plasma and saliva
  • Expertise in LC-MS, quantitative NMR for glycans and glycopeptides, detailed glycan characterisation via exoglycosidase sequencing




Collaborative Projects:

Ludger-GlySign

2016-2020

GlySign - EU Horizon 2020 research and innovation programme (Marie Sklodowska-Curie grant agreement No 722095): a research training network on glycomic clinical markers and assay development for Precision Medicine.

The importance of glycomics to healthcare is summarised in a recent report endorsed by the US Academies which stated that "glycans are directly involved in the pathophysiology of every major disease" and that "additional knowledge from glycoscience will be needed to realize the goals of precision medicine and to take advantage of the substantial investments in human genome and proteome research and its impact on human health". The name GlySign refers to the distinctive and complex changes in the glycomics profiles or 'Glycan Signatures' of the body's glycoproteins that occur during progression of many chronic diseases including cancers and inflammatory conditions. GlySign aims to train skilled glycomics specialists and offers 6 PhD positions for EarlyStage Researchers (2 based at Ludger). Ludger is joined in the GlySign consortium by Genos and Leiden University Medical Center.

www.glysign.eu




ludger-GlyCoCan

2015-2019

GlyCoCan - EU funded Marie Curie European Training Network: Exploiting Glycosylation of Colorectal Cancer for the development of improved diagnostics and therapeutics.

Colorectal cancer (CRC) is the second most common cancer in Europe and is one of the most curable cancers when detected in its early stages. However, the heterogeneous nature of CRC leads to highly variable disease progression and outcome as well as treatment response, resulting in an urgent need for personalized treatment and biomarkers. GlyCoCan will enhance our understanding on the structure-function relationship of glycosylation in CRC. The goal is to discover improved diagnostic and prognostic biomarkers and pave the way for novel therapeutic targets.

https://glycocan.eu/




ludger-innovate uk

Feb 2017- Jan 2018

GlycanDx-MODY: Biomedical Catalyst 2016 - Feasibility Study grant funding from Innovate UK, for a glycomics precision diagnostic assay for Maturity Onset Diabetes of the Young (MODY)

MODY affects 1-4% of the diabetes patient population and it is estimated that at least 90% MODY patients are misdiagnosed and therefore, often prescribed ineffective treatment. A clinical diagnostics 'MODY' assay has been developed to identify patients with the most common form of MODY, HNF1A-type. These patients have reduced plasma outer arm fucosylation which is caused by defects in the HNF1A gene. The MODY assay is a plate based biochemical assay which provides a faster and more affordable alternative to genetic testing.

This exciting project, named GlycanDx-MODY, will be led by Ludger Ltd and includes the following partners; Genos (Croatia) and OCDEM (Oxford University, UK). The goal is to develop a clear business and technology plan for this assay to facilitate its incorporation into a diagnostic pathway for MODY which will ultimately be adopted by healthcare providers at the primary care level.






Ludger-GlycoPar

2013-2017

GlycoPar - EU FP7-funded Marie Curie Initial Training Network on parasite glycobiology.

Protozoan parasites and helminths are the cause of some of the most devastating diseases worldwide and a major effort is needed to be able to control or eliminate these diseases. Glycoconjugates are present on the surface of many parasites and they are frequently involved in their survival strategies by forming a protective barrier against host defences. GlycoPar has been set up to study parasite glycobiology in detail and translate this research into successful therapeutic strategies.

www.glycopar.eu




Ludger-IBDBIOM

2012-2016

IBD-BIOM - EU FP7-funded programme for development of glycan based clinical diagnostics for patients with inflammatory bowel diseases.

The aim of IBD-Biom is to discover new, more reliable clinical biomarkers for IBD to allow the early diagnosis of patients and to point to possible molecular targets for new, improved therapies for patients. To date, genome-wide association studies have identified around 100 IBD susceptibility loci but clinical application has been limited. In this programme, an IBD biomarker discovery and assay system (IBD-BDAS) will be developed and used for biological samples from 6000 well characterised IBD patients and controls with the aim of identifying possible biomarkers.

www.ibdbiom.eu







Relevant posters and papers:


Jenner HT O-Glycosyaltion Analysis Poster

Development of a High Throughput Method for
O-Glycosylation Analysis

Kotsias M, Gardner R, Kozak RP, Wuhrer M, Spencer D
Presented at: 12th Jenner Glycobiology and Medicine Symposium: Translational Glycobiology
Dubrovnik, Croatia. May 6-9th 2017

Keywords: Colorectal cancer (CRC), O-glycosylation, permethylation, MALDI-TOF-MS, high throughput analysis, GlycoCan




Ludger GlycoPar 2016 poster

Procainamide labelling as part of a sensitive workflow for the identification and quantitation of potential glycan drug targets in parasite cell membrane, insect vector saliva and host tissue models of infection by HILIC-HPLC-ESI-MS/MS

Wongtrakul-Kish K, Kozak RP, Spencer D
Presented at the GlycoPar Symposium & Workshop
Liverpool, UK. Sept 12-14th 2016

Keywords: Procainamide, LC-MS, HILIC-HPLC-ESI-MS/MS, parasitic glycans, insect vector glycans, host glycans, GlycoPar




Ludger GlycoPar 2016 poster

First steps in the development of a high throughput method for O-glycosylation analysis

Kotsias M, Kozak RP, Shubhakar A, Fernandes DL, Spencer D
Presented at the GlycoPar Symposium & Workshop
Liverpool, UK. Sept 12-14th 2016

Keywords: Colorectal cancer (CRC), O glycans, permethylation, MALDI-TOF-MS, GlycoCan






Ludger poster

Investigating the role of insect vector glycosylation in African sleeping sickness transmission: Characterisation of procainamide-labelled tsetse fly saliva N-glycans

Kozak RP, Wongtrakul-Kish K, Williams C, Fernandes DL, Perally S, Rose C, Spencer DI, Acosta-Serrano A
Presented at Glyco23: 23rd International Symposium on Glycoconjugates
Split, Croatia. September 2015

Keywords: trypanosomiasis, saliva, 2AB, procainamide, UHPLC, ESI-MS/MS




Ludger poster

Investigating the role of insect vector glycosylation in African sleeping sickness transmission: Characterisation of procainamide-labelled tsetse fly saliva N-glycans

Kozak RP, Wongtrakul-Kish K, Williams C, Perally S, Rose C, Spencer DI, Acosta-Serrano A
Presented at:
Gordon Research Conference
Lucca, Italy. March 2015
and CASSS Analytical Technologies Conference
Berlin, Germany. March 2015




Ludger poster

Studies on Salivary Glycosylation

Urbanowicz PA, Kozak RP, Fernandes DL
Presented at ACTA: 10th European Symposium on Saliva
Egmond aan Zee, Netherlands. May 2014

Keywords: saliva, O glycans, Orela, 2AB, glucose homopolymer standard, T1 cartridges, UHPLC, MALDI-MS








Contacts

R&D Programmes

Dr. Daniel Spencer

Dr. Daniel Spencer
Head of Development
daniel.spencer@ludger.com