A multidisciplinary training network for the bioinspired development of glycomimetics tuning the Siglec-Sialoglycan axis

Project Information

GLYTUNES

Grant agreement ID: 956758

DOI

10.3030/956758

Project closed

EC signature date 13 August 2020

Start date 1 March 2021

End date 28 February 2025

Funded under

• EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions

Total cost

€ 3 744 223,56

EU contribution

€ 3 744 223,56

Coordinated by

UNIVERSITA DEGLI STUDI DI NAPOLI FEDERICO II
Italy

Periodic Reporting for period 2 - GLYTUNES (A multidisciplinary training network for the bioinspired development of glycomimetics tuning the Siglec-Sialoglycan axis)

Reporting period: 2023-03-01 to 2025-02-28

Summary of the context and overall objectives of the project

The GLYTUNES program is tackling the growing need for the development of new diagnostic and therapeutic strategies infectious, cancer, and autoimmune diseases within the biotech, healthcare, and pharmaceutical sectors. To achieve this, GLYTUNES has created a collaborative, interdisciplinary training program in Europe, led by experts and working closely with industry partners in the EU.
The project recognizes that glycoscience—the study of sugars and their roles—is now vital in modern medicine, especially for developing diagnostic tools and therapies. A key focus is on understanding how glycans (sugar molecules) and glycosylation (a crucial process where sugars are added to other molecules, influencing their function) affect the immune system. This knowledge is crucial for improving our understanding of how immune diseases develop and progress.
Specifically, GLYTUNES has investigated Siglecs, a type of receptor on immune cells that interacts with sialylated glycans (sugars containing sialic acid). These interactions play a critical role in regulating the immune system, influencing whether it triggers an immune response or tolerates certain molecules. Research over the past decade has revealed that disruptions in Siglec-sialylated glycan interactions are linked to various diseases, including infections, autoimmune disorders, and cancer. Therefore, the Siglec-sialoglycan axis is a promising target for developing new treatments.
The main goal of GLYTUNES has been to generate new knowledge and provide advanced training to:
• Understand how Siglecs and their sialylated ligands interact in immune-related diseases at a molecular and dynamic level.
• Develop new therapeutic approaches by designing glycomimetics (molecules that mimic glycans) to precisely modulate the Siglec-glycan axis.

Work performed from the beginning of the project to the end of the period covered by the report and main results achieved so far

The GLYTUNES project has recruited 14 early-stage researchers and provided them with training in research and development, including consortium-wide training, personalized training, and training in entrepreneurship, management, presentation skills, and ethics. The consortium includes 7 academic partners and 4 companies from 7 European countries, bringing together expertise in various fields such as carbohydrate chemistry, structural biology, drug design, and immunology.
The research has been organized into four main areas:
• Production of sialylated ligands: This has involved isolating and synthesizing endogenous (from the body) and exogenous (bacterial) sialylated ligands, then used in binding and immunological studies.
• Depiction of 3D complexes: This has focused on understanding the molecular basis of how Siglecs bind to their ligands using techniques like NMR spectroscopy, X-ray crystallography, and CryoEM.
• Immunological studies: aimed at understanding the immune mechanisms and signaling pathways involved in Siglec-ligand interactions.
• Development of novel glycomimetics: centered on designing and synthesizing new glycomimetics to modulate Siglec activity.
Each researcher has worked on a unique project supervised by a multidisciplinary team, combining expertise and technology from across the consortium.

Progress beyond the state of the art and expected potential impact (including the socio-economic impact and the wider societal implications of the project so far)

Significant progress has been made in defining the structure, conformation, and properties of Siglec ligands, isolating and purifying glycan libraries, expressing and characterizing Siglecs (Siglec-2, Siglec-10, Siglec-7, Siglec-9 among the others), describing 3D complexes, performing immunological studies, and designing glycomimetics. This interdisciplinary effort combined chemical, biological, biophysical, and immunological research strategies.

GLYTUNES trained 14 ESRs in a highly integrated and collaborative environment, underpinned by extensive interactions between academic and industrial partners and by their experience in higher education, training and mentoring, and endowed with state-of-the art scientific and technical expertise and infrastructures. The ESRs have acquired scientific and transferable skills to make them highly competitive and new leaders in top EU academia and research institutions, healthcare and biotech job markets.

The combined multidisciplinary and glycobiotechnological approach of GLYTUNES