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Unravelling Glycosylation Codes in Cancer at the Molecular Level: An Interdisciplinary Approach for the Dissection of the Recognition Features of CD44 by Galectins and Selectins

Project description

Protein modifications and tumour progression

Proteins on the surface of cancer cells are frequently modified with abnormal sugar moieties through a process called aberrant glycosylation. Accumulating evidence indicates that aberrant glycosylation promotes tumour growth, immune evasion and metastasis. CD44 is a protein highly expressed in breast and colon cancer whose glycosylation influences the way it interacts with other molecules in the tumour microenvironment. With the support of the Marie Skłodowska-Curie Actions programme, the GLYCODECD44 project aims to investigate at atomic resolution how specific sugar structures on CD44 determine its recognition by carbohydrate-binding proteins called lectins. Researchers will use advanced nuclear magnetic resonance spectroscopy and biochemical tools to define the molecular interfaces governing these interactions. Results will ultimately reveal how aberrant glycosylation contributes to cancer-promoting signalling.

Objective

GLYCODECD44 aims to elucidate, at atomic resolution, how distinct glycan species on CD44 drive recognition by galectins and selectins, and how this translates into functional outcomes in the context of breast and colon cancer. Defined CD44 glycoforms will be generated to elucidate how glycan composition and presentation within the full glycoprotein context, determines specific recognition by lectins, and to understand the role of aberrant glycosylation in cancer

Isotopically labelled CD44 ectodomains bearing chemically defined tumour-relevant N- and O-glycan motifs through glycoengineering and chemoenzymatic remodeling will be generated to deduce the molecular interfaces, dynamics, and affinities of CD44 binding to selected galectins and selectins by employing state-of-the-art NMR experiments, complemented with ITC and BLI. Finally, the way that molecular recognition features elucidated in vitro affect the nature of the interaction on the cell-surface will be revealed.

Moreover, solidly based on the scientific aspects, the action will offer Dr Padilla a deep knowledge on the power of interdisciplinary research, particularly focused on glycosciences. It will provide him synergic expertise in Molecular Recognition, Biological Chemistry, and Glycobiology, allowing him to gain a high level of research independence and capabilities and develop a set of soft skills. It will also allow him to participate in international collaborations and reinforce his research networks. Altogether, these elements will strengthen a solid long-term competitiveness, essential for his forthcoming scientific career. Simultaneously, the host lab will highly benefit from Dr Padilla’s experience on NMR of macromolecular receptors and biophysics, key for the development of the project.

Fields of science (EuroSciVoc)

Keywords

Programme(s)

Topic(s)

Funding Scheme

HORIZON-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European Fellowships

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Call for proposal

(opens in new window) HORIZON-MSCA-2025-PF

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Coordinator

ASOCIACION CENTRO DE INVESTIGACION COOPERATIVA EN BIOCIENCIAS CIC BIOGUNE
Net EU contribution
€ 194 074,56
Address
PARQUE TECNOLOGICO EDIFICIO 801 A
48160 DERIO VIZCAYA
Spain
Region
Noreste País Vasco Bizkaia
Activity type
Research Organisations
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Total cost
No data