Glycobiochemistry
Head: prof. RNDr. Michaela Wimmerová, Ph.D.
Research Topics
Carbohydrates are essential for life and, in addition to their conventional roles as structural and energy storage components, they act as important information molecules with enormous coding capacity. This fact is given by their stability and the stereochemical diversity of the glycosidic bonds connecting individual sugar units. As such, carbohydrates play crucial roles in the recognition events at both molecular and cellular levels. Specific recognition of glycoconjugates is important in the biological systems and participates in numerous physiological (cell signaling, cell differentiation, morphogenesis, inflammatory response) and pathophysiological processes (cancerogenesis, host-pathogen interactions).
The research is focused on the structure-functional studies of proteins that participate in the oligosaccharide synthesis (glycosyltransferases) and specific carbohydrate recognition (lectins). The emphasis is placed on proteins from obligate and opportunistic pathogens that are related to the virulence/pathogenicity of the organism, and on searching for new lectins with interesting sugar-binding specificities or biological properties.
For the study of lectins and glycosyltransferases, a multidisciplinary approach is used. New protein targets are identified by bioinformatical tools and prepared in the recombinant form using molecular biology approaches. Biophysical techniques (ITC, SPR, MST) and high-resolution X-ray crystallography are used to decipher the thermodynamic and structural basis for the binding of carbohydrates. Such a structure-function correlation of protein/carbohydrate interaction forms the basis for the rational design of carbohydrate-based drugs directed against adhesion and virulence.
Research Areas
- Carbohydrate-binding proteins involved in host-pathogen and symbiotic interactions
- Lectins as tools for glyco-profiling of cells and detection of glycosylation changes associated with different physiological/pathological conditions
- Protein engineering of lectins
- Human glycosyltransferases and their role in cancerogenesis
- Glycosyltransferases participating in mycobacterial cell wall synthesis
- Biomolecular interactions
Main Objectives
- Investigating the structures of lectins and glycosyltransferases, their interactions with carbohydrates, and their relations to the functions of living systems, disease, and therapy.
- Studying the therapeutical aspects of recognition and adhesion phenomena in host-pathogen and symbiotic interactions. Testing of new carbohydrate-based drugs directed against adhesion and virulence of the pathogen.
