Scientific Programme

INTERNATIONAL SCHOOL OF NANOMEDICINE

INNOGLY WG2:

THE GLYCOBIOLOGY OF CELL
METABOLIC PROCESSES
AT THE NANOSCALE IN HUMAN

PATHOLOGY
July 19-24, 2023

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A) The aim of INNOGLY COST action is to build up a multidisciplinary group of researchers to address the same pioneering goal: Gaining new insight into the biological function of glycans in different biological contexts. Innogly addresses the following two main topics:

1. Glycan profiling in health and disease, where studies will be more specifically focused on glycan-based correlations in developmental and cancer biology, and glycan dependent modulation of the auto/endo-lysosomal system with focus on lysosomal diseases, cancer and neurodegenerative diseases

2. Glycan-based diagnostics and therapeutics, where INNOGLY investigators will focus on glycan dependent fine tuning of immunity-

B) WG2 of the INNOGLY consortium is focused on the understanding of how changes in the glycome of the auto/endo-lysosomal system cause disease, as in lysosomal diseases, cancer, neurodegenerative diseases. WG2 is also focused on the glycan-based diagnostics and therapy of these diseases.

More detailed explanation:

1. The glycome of the auto/endo-lysosomal system is here defined as the whole array of structures which contain two or more cyclic carbohydrates covalently linked together, including glycolipids, glycoproteins, proteoglycans, oligosaccharides, glycosaminoglycans, polysaccharides, DNA/RNA etc. Where glycans are part of a larger complex, as in glycoproteins, the glycan part is the focus of attention.

2. The glycome of the auto/endo-lysosomal system is among the most complex, dynamic and heterogenous in any part of the organism. The origin of this glycome is not only a result of the biosynthetic machinery of the cell, but the uptake of extracellular glyco-material via endocytosis/phagocytosis, and the myriads of partially digested glycans resulting from lysosomal hydrolysis. This results in an almost incomprehensible number of different structures. The auto/endo-lysosomal system of the macrophages may exhibit the most complex glycome, due to the high extracellular uptake.

3. The need to regulate the concentration of each individual glycan-structure of the auto/endo-lysosomal glycome is best appreciated by the pathological consequences of lysosomal diseases resulting from deficiencies of glycan-processing hydrolases, as in alpha mannosidosis and Tay-Sachs disease. The clinical diversity of these and other glycome-abnormalities suggests that the type and concentration of accumulating glycans are pivotal contributors to the pathology.

4. The role of glycomic changes in complex disorders, as cancer, rheumatic diseases, CNS-diseases etc., is incompletely understood. Nevertheless, since changes in the glycome of the auto/endo-lysosomal system occurs in many complex disorders, they are likely to contribute to the pathology.

5. There is an insufficient understanding on the molecular mechanisms leading to pathology glycome abnormalities of the auto/endo-lysosomal system, for example the molecular pathomechanism of inflammation. As our understanding is increasing, improved treatments and glycan-based diagnostics can be developed.

The goal of this training school is to give European students insights into the secrets of the glycome of the auto/endo-lysosomal system, and demonstrate how abnormalities in the glycome cause human disease. Glycan based diagnostics and therapies to restore the glycome composition will be presented. The aim is also to foster collaborations among students in different laboratories and countries, each of them spurred to pursue his own research interests, in order to move forward new ideas and approaches to address glycan-related scientific challenges from wide perspectives. The interplay between students and teachers at the training school provides an unique opportunity to a life-long friendships and courage by the students in their early career, to dive into complex research, knowing that there is always an experienced person to ask for advice As an extra challenge for this training school, we aim that the school provides a suggestion for a topic of a new COST consortium, to continue the collaboration and deep dive into the unknown territory of the glycome of the auto/endo-lysosomal system and its relationship to pathology, diagnosis and therapy.