PhD projects within GlyCoCan:
Glycoproteomic analysis of cell surface and secreted glycoproteins from colorectal cancer cell lines (The Netherlands)
Aim of the project
The project aims, first of all, at the design and optimization of a robust, (high-throughput) glycoproteomics workflow for the analysis of cell surface and secreted glycoproteins from CRC cell lines. This will provide insight into differentially expressed/glycosylated proteins associated with CRC development. Finally, differentially expressed/glycosylated proteins will be evaluated as targets for (genetic) manipulation to study their functional importance to CRC development. More information (PDF)
PhD student Martina Pirro
Supervisor P. Hensbergen
LUMC, Center for Proteomics and Metabolomics
The Netherlands
Functional relationship of CRC-associated glycans with malignant phenotype and transcriptome changes (Italy)
Aim of the project
The project aims, first of all, at the identification of gene expression signatures associated with specific glycosylation changes in CRC tissues and cell lines. Secondly, the data produced during research will pinpoint phenotypic changes specifically associated with the expression of glycosyltransferases and of sugar structure expression. Finally, interactions between cancer cells and the immune system will be further elucidated. More information (PDF)
PhD student Inês Gomes Ferreira
Supervisor F. Dall’Olio
University of Bologna, Laboratory of Glycobiology
Italy
Development of a chemical reporter strategy to define the dynamics of intake and utilisation of monosaccharides in colorectal cancer cells (France)
Aim of the project
The project aims at linking monosaccharide uptake/metabolism to glycome expression: how different monosaccharides are scavenged and used differently in cancer / non-cancer cells, and how this influences the aggressiveness of the tumor. The effect on the glycan metabolic fluxes and glycan expression of known anti-cancer drugs and glycosylation-impairing chemicals will be assessed, to finally better understand the relationships between glycosylation and cancer and how anti-cancer drugs influence glycan metabolism, synthesis and expression. More information (PDF)
PhD student James Biwi
Supervisor Y. Guérardel
Université de Lille, Unité de Glycobiologie Structurale et Fonctionnelle
France
Automated techniques for assessment of novel O-linked glycan-associated biomarkers from colorectal cancer tissues (United Kingdom)
Aim of the project
The project aims at the optimization of a workflow for O-glycan extraction from both cancer cell line models and tissue samples. HPLC and MS-based methods will be used for profile analysis and glycan/glycopeptide characterization. Finally, automated and validated analysis methods for colorectal biomarker glycans, from both plasma and tissue samples will be developed. More information (PDF)
PhD student Maximilianos Kotsias
Supervisor D. Spencer
LUDGER LTD
United Kingdom
Towards personalised medicine: Investigating Colon Cancer Tissue glyco-microheterogeneity in individual CRC specimens using FFPE-sections (Germany)
Aim of the project
The project aims at developing a robust analytical workflow for N- and O- glycomics based on histopathological FFPE slides. The analysis will allow the establishment of a high-quality CRC-glycan library, also available to the public and will finally shed light onto CRC-specific glycosylation signatures and microheterogeneity with diagnostic/prognostic potential. More information (PDF)
PhD student Katarina Madunic
Supervisor D. Kolarich
Max Planck Institute of Colloids and Interfaces, Glycoproteomics
Germany
Structural characterization of colorectal cancer cell glyco-signature(s) contributing to the polarization of macrophages (France)
Aim of the project
This project aims at elucidating the impact of colorectal cancer cell (CRC) glycosylation on the modulation of the immune system with a specific focus on monocytes and macrophages. The influence of various CRC cell lines on the monocyte-to-macrophage differentiation and polarization of macrophages will be tested in vitro and then correlated with the glycan features of CRC cell lines determined beforehand by mass spectrometry and transcriptomics. Once glycoantigens with an immunological role have been identified, they will be validated by using the purified glycoantigens as well as genetically-modified CRC cell lines positive or negative for glycoantigens, and through the identification of glycan-binding receptors on monocytes/macrophages recognizing the CRC glycoantigens. More information (PDF)
PhD student Giulia Trimaglio
Supervisor Y. Rombouts
University of Toulouse, Institute of Pharmacology and Structural Biology
France
Evaluation of the in vitro and in vivo immune modulation of tumorigenic Lewis Antigens on dendritic cells (The Netherlands)
Aim of the project
The project will start with the generation of a panel of Lewis antigen negative and positive CRC cell lines, which will then be glycoprofiled as well as screened with specific C-type lectins. Human dendritic cells exposed to these cell lines will undergo functional assessment. In vivo evaluation of immune cell infiltration into the differently glycosylated CRC tumors will provide the final proof of concept that the Lewis – C-type lectin interactions contribute to immune escape in CRC. More information (PDF)
PhD student Athanasios Blanas
Supervisor S.van Vliet
VU University Medical Center Amsterdam, Molecular Cell Biology and Immunology
The Netherlands
In vitro and in vivo studies of the role of Lewis antigens in selectin binding and trans-endothelial migration (Portugal)
Aim of the project
The project aims to study the role of CRC glycosylation in cell migration, growth and immunemodulation. Specifically, to elucidate the molecular effectors that allow cancer cells to bind endothelial and leukocyte selectins. We will identify and isolate selectin ligands, and assess in vitro and in vivo its role on the binding of CRC cells to leukocyte and endothelium and its metastasizing profiles. More information (PDF)
PhD student Fanny Deschepper
Supervisor P. Videira
Faculdade de Ciências e Tecnologia, Universidade Nova de Lisboa
Portugal
Development and in vitro and in vivo validation of novel antibodies for Lewis antigens (Portugal)
Aim of the project
The project aims to evaluate the therapeutic potential of antibodies against CRC-associated antigens, namely Lewis antigens. We will evaluate existing antibodies for in vitro anti-tumour efficacy.. Newly developed antibodies, obtained by phage display library or hybridoma technology, will be characterized in vitro and in vivo. We will develop luciferase-expressing CRC cell lines to be used as xenografts in animal models. More information (PDF)
PhD student Roberta Zoppi
Supervisor P. Videira
Faculdade de Ciências e Tecnologia, Universidade Nova de Lisboa
Portugal
Haptoglobin glycosylation in CRC (Croatia)
Aim of the project
The project aims at the development of a robust high-throughput analytical workflow for analysis of haptoglobin glycosylation (N-glycome by HILIC; N- and O- glycomics, site specific N-glycosylation by LC-ESI-MS/MS). Establishment of a high throughput MS based assay for targeted and quantitative glycopeptide marker analysis using synthetic glycopeptides After establishment of a comprehensive site-specific glycosylation map for haptoglobin isolated from healthy controls and CRC patients, a high-throughput screening of CRC specific haptoglobin glycopeptide signatures will result in a thorough evaluation of this plasma protein for its prognostic/biomarker potential in CRC diagnosis, patient stratification and patient survival. More information (PDF)
PhD student Jelena Šimunović
Supervisor: G. Lauc
GENOS
Croatia
Total plasma, IgG and IgA glycosylation in CRC and inflammatory bowel disease (IBD) for prognosis, patient stratification and differential diagnosis (Croatia)
Aim of the project
The project aims at a systematic comparative analysis of CRC, IBD patients’ and healthy controls’ plasma N-glycome (by HILIC), as well as peripheral blood IgG N-glycome and IgA N- and O-glycome (by LC-ESI-MS). In a second step, a thorough evaluation of the prognostic and biomarker value of these biological traits will provide insight into their use for (differential) diagnosis, patient stratification and patient survival. More information (PDF)
PhD student Ana Momčilović
Supervisor M. Pucic Bakovic
GENOS
Croatia
N-glycosylation of CEA and TIMP-1 as colorectal cancer biomarkers (The Netherlands)
Aim of the project
First, the project aims at the development of a systematic method for high-throughput sample preparation of carcinoembrionic antigen (CEA) and tissue-inhibitor of metalloproteinase 1 (TIMP-1) from from human plasma, followed by high sensitivity MS analysis of glycosylation. Second, the method will be applied for the characterization of CEA and TIMP-1 from both colorectal cell lines and plasma samples of patients, evaluating the potential in early detection and disease prognosis. More information (PDF)
PhD student Valeria Kuzyk
Supervisors M. Wuhrer and G.W. Somsen
Vrije Universiteit Amsterdam, Divison of BioAnalytical Chemistry
The Netherlands
Establishing a chemo-enzymatic platform for the synthesis of highly defined glycopeptide standards (Germany)
Aim of the project
First of all the project aims at the production of a library of glycosylated Fmoc-protected asparagine building blocks isolated from natural sources for solid phase glycopeptide synthesis. Secondly, following in silico sequence screening, a library of immobilized recombinant glycosyltransferases will be established and characterized for activity and stability. The two libraries, combined with a comprehensive dataset of the in vitro activity of the enzymes and their influencing factors, will form the platform for the synthesis and highly selective tailoring of glycoconjugates. More information (PDF)
PhD student Hyun Il Oh
Supervisor D. Kolarich
Max Planck Institute of Colloids and Interfaces, Glycoproteomics
Germany