CARMUSYS · Carbohydrate Multivalent Systems as tools to study Pathogen interaction with DC-SIGN

The importance of glycosciences in the development of biology and medicine and the central role played by chemistry in this process have recently been pointed out by ESF. However, it appears that exposure of young scientists in their training phase to the chemical biology of carbohydrates is still lacking. This multidisciplinary project intends to approach the design and synthesis of carbohydrate multivalent systems to be used as tools to study the interaction between carbohydrates and DC-SIGN (Dendritic Cell-Specific ICAM-3 Grabbing Non-integrin), a C-type lectin implicated in the recognition of pathogens and in some of the earliest stages of the infection process. Targeting pathogens at the earliest stages of infection, before cell penetration, is of crucial importance because it can result in a significant decrease of pathogen titre in the organism and therefore will facilitate the efficiency of current therapies. The role that DC-SIGN plays in the immune response through the interaction and recognition of pathogens leads to a very complex pathway of signalling cascade that could be modulated using these carbohydrate multivalent systems as effectors. Thus the studies we propose could provide the background for the design, selection and preparation of better antiviral drugs and could afford new insights to unravel the complex mechanisms of the immune system, thus opening a strategy to develop vaccines through the modulation of dendritic cells activity. To reach these goals, a highly interdisciplinary group of scientists (synthetic chemists, computational chemists, biochemists, immunologists, etc.) has been assembled, some of whom are already collaborating on the topic. The planned flow of information between laboratories and the network-wide training activities described in this proposal will create an unrivalled environment for training of young scientists in glycosciences.