Glycoproteomics of stress and stress-associated diseases

Glycosylation is the most complex posttranslational modification that was apparently crucial for the development of multicellular life. Almost all proteins that evolved after the appearance of multicellular organisms are glycosylated and glycans represent significant part of their molecular structure. However, due to high complexity of glycan structures, the level of knowledge about glycans lags significantly behind the level of knowledge about proteins and DNA. Since a glycoprotein interacts with other molecules as an integral molecule where biosynthetic origin of its individual parts is not relevant, the lack of knowledge about glycan structures is a large obstacle to the understanding of biological processes. Molecules in which the role of glycan was studied in detail clearly demonstrate that in addition to structural roles, glycans frequently have regulatory roles, and that they modulate many physiological and pathophysiological functions.
Stress response is very complex process through which our organism prepares for treats (real or imagined)in the environment. Excessive stress is associated with the appearance and development of numerous diseases. Published data and our previous results indicate that changes of glycosylation are involved in the molecular mechanisms of the stress response. In many stress-related diseases, specific changes of glycosylation have been demonstrated, but it is mostly unknown whether these changes are just a reflection of changed cellular metabolism, or some of these changes also have a role in the etiology of a disease. The aim of this project is to study changes in protein glycosylation, the activity and expression of their lectin receptors, and the expression of genes responsible for glycan synthesis in different pathobiochemical processes and to determine to what extent these changes affect their appearance and course. Genetic polymorphisms of some key glycosyltransferases will be studied and correlated with stress-associated diseases. Tests will be conducted on patients’ blood samples, in animal models of stress and inin vitro models. In stress the line between adaptation and mal-adaptation is rather thin, and it seems that glycosylation plays an important role in crossing that line. Through suggested multidisciplinary research plan, we expect to partially enlighten these very complex processes and discover potential targets for the development of specific drugs that could alleviate adverse effects of stress.