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In silico investigation of the functional role of sugars in the host-pathogen interactions

English title In silico investigation of the functional role of sugars in the host-pathogen interactions
Applicant Lisacek Frédérique
Number 141215
Funding scheme Project funding
Research institution Institut Suisse de Bioinformatique Centre Médical Universitaire Université de Genève
Institution of higher education Swiss Institute of Bioinformatics - SIB
Main discipline Molecular Biology
Start/End 01.09.2012 - 31.08.2014
Approved amount 278'667.00
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All Disciplines (3)

Discipline
Molecular Biology
Medical Microbiology
Information Technology

Keywords (6)

host-pathogen; glycomics; sugar epitope; bioinformatics; body fluids; mass spectrometry

Lay Summary (English)

Lead
Lay summary

The initial cellular contact between a target cell and an invading pathogen was shown to involve one or more protein-sugar interactions, but the molecular basis for cell-cell interactions remains poorly understood. In spite of its central role in biological studies, glycomics has lagged behind other -omics mostly because, until recently, methods for characterising the branching structures of complex carbohydrates had not been developed. The gap is being filled with the development of mass spectrometry (MS) and high performance liquid chromatography (HPLC) as efficient analytical techniques. Databases and comparative tools are needed for the automated annotation of structures based on regular features detected in spectra or glycan profiles. Then, the systematic comparison of known and newly identified glycans and sugar epitopes will bring out structural and functional variations depending on protein data, microbial species and selected tissues. These variations can be scored and tentatively categorised in the prospect of the molecular characterisation of microbial carbohydrate-binding proteins and oligosaccharide/protein epitopes in infectious diseases. The project will result in a publicly available bioinformatics platform validated with the study of mammalian sugar epitopes. It will also bring out biological evidence of sugar antigenicity through a comparative study of several bacterial systems. The experimental data processing will not only reflect as closely as possible the analysis of human experts but it will also set the basis for the development of other glycomics applications involving diseases such as cancer.

Direct link to Lay Summary Last update: 21.02.2013

Responsible applicant and co-applicants

Employees

Publications

Publication
MzJava: An open source library for mass spectrometry data processing
Horlacher Oliver (2015), MzJava: An open source library for mass spectrometry data processing, in Journal of Proteomics, 129, 63-70.
Toolboxes for a standardised and systematic study of glycans.
Campbell Matthew P, Ranzinger René, Lütteke Thomas, Mariethoz Julien, Hayes Catherine A, Zhang Jingyu, Akune Yukie, Aoki-Kinoshita Kiyoko F, Damerell David, Carta Giorgio, York Will S, Haslam Stuart M, Narimatsu Hisashi, Rudd Pauline M, Karlsson Niclas G, Packer Nicolle H, Lisacek Frédérique (2014), Toolboxes for a standardised and systematic study of glycans., in BMC bioinformatics, 15 Suppl 1, S9.
GlycoDigest: a tool for the targeted use of exoglycosidase digestions in glycan structure determination.
Gotz Lou, Abrahams Jodie L, Mariethoz Julien, Rudd Pauline M, Karlsson Niclas G, Packer Nicolle H, Campbell Matthew P, Lisacek Frederique, GlycoDigest: a tool for the targeted use of exoglycosidase digestions in glycan structure determination., in Bioinformatics (Oxford, England).
SugarBindDB, a resource of pathogen lectin-glycan interactions
Mariethoz Julien, Kahtib Khaled, Campbell Matthew P, Packer Nicolle H, Mullen Elaine, Lisacek Frederique, SugarBindDB, a resource of pathogen lectin-glycan interactions, in Taniguchi Naoyuki (ed.), Springer-Verlag, SpringerReference, Berlin Heidelberg.
UniCarbKB: an emergent knowledgebase for glycomics
Campbell Matthew P, Peterson Robyn, Gasteiger Elisabeth, Mariethoz Julien, Lisacek Frederique, Packer Nicolle H, UniCarbKB: an emergent knowledgebase for glycomics, in Taniguchi Naoyuki (ed.), Springer-Verlag, SpringerReference, Berlin Heidelberg.
UniCarbKB: Building a knowledge platform for glycoproteomics
Campbell Matthew P, Peterson Robyn, Mariethoz Julien, Gasteiger Elisabeth, Akune Yuki, Aoki-Kinoshita Kiyoko F, Lisacek Frederique, Packer Nicolle H, UniCarbKB: Building a knowledge platform for glycoproteomics, in Nucleic Acid Research, 42(1), D215-D221.
UniCarbKB: First Year Report Card
Campbell Matthew P, Perterson Robyn, Gasteiger Elisabeth, Zhang Jin, Akune Yuki, Abrahams Jodie L, Mariethoz Julien, Karlsson Niclas, Aoki-Kinoshita Kiyoko F, Lisacek Frederique, Packer Nicolle H, UniCarbKB: First Year Report Card, in Hicks Martin G (ed.), Beilstein Institute Publications, Frankfurt.

Collaboration

Group / person Country
Types of collaboration
Biomolecular Frontiers Research Centre, Faculty of Science, Macquarie University, Sydney Australia (Oceania)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
- Research Infrastructure
National Institute for Bioprocessing Research & Training, Conway Institute, Dublin Ireland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
Medical Biochemistry, University of Gothenburg Sweden (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
- Research Infrastructure

Scientific events

Active participation

Title Type of contribution Title of article or contribution Date Place Persons involved
5th Warren Workshop Talk given at a conference Managing contextual information in glycobioinformatics resources 04.08.2014 National University, Ireland Lisacek Frédérique;
Annual conference of European Proteomics Association, EuPA 2013 Talk given at a conference UniCarbKB: a knowledge platform for glycoproteomics 14.10.2013 Saint-Malo, France Lisacek Frédérique;
Beilstein Glycobioinformatics Workshop 2013 Talk given at a conference Update of SugarBindDB 11.06.2013 Beilstein Institute, Postdam, Germany Mariethoz Julien;
Systems Biology Approach to Infectious Processes Talk given at a conference On-line knowledge of glycans involved in infection 13.05.2013 University of Lyon 1, France Lisacek Frédérique;
3rd meeting of COST Action FA1002 Farm Animal Proteomics Talk given at a conference Detection and annotation of common post-translational modifications in mass spectrometry data 24.04.2013 Kosice, Slovakia Lisacek Frédérique;
Proteomic Forum 2013 Talk given at a conference UniCarbKB: a knowledge platform for glycoproteomics 18.03.2013 Berlin Free University, Germany Lisacek Frédérique;
Theoretical Approaches for the Genome and the proteins, TAGp2012 Talk given at a conference Tuning and mediating protein-protein interactions 03.12.2012 in2p3, Annecy, France Lisacek Frédérique;
PROSPECTOM 2012 Talk given at a conference UniCarbKB: a knowledge platform for glycoproteomics 29.11.2012 Grenoble, France Lisacek Frédérique;
Network Tools and Applications in Biology, NETTAB 2012 Poster Glycans, the forgotten biomolecular actors of the big picture 14.11.2012 Como, Italy Mariethoz Julien; Lisacek Frédérique;


Communication with the public

Communication Title Media Place Year
Other activities Fête des Maths 2014 de l'Association Ainterremaths Western Switzerland International 2014
New media (web, blogs, podcasts, news feeds etc.) Towards a systems biology of gastric cancer International 2013

Abstract

This project aims at analysing mass spectrometry data and characterising the functional role of sugars through the systematic comparison of antigenic sugar (sub-)structures in body fluids. It will help refine the molecular characterisation of microbial carbohydrate-binding proteins and oligosaccharide/protein epitopes in infectious diseases. It will also result in a predictive platform for mammalian sugar epitopes.
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