Marine Polysialyltransferases for the Generation of Immunomodulatory Bioconjugates

Contact: PD Dr. biol. hom. Sebastian Peter Galuska

Duration: 2022-2025

Funding: Deutsche Forschungsgemeinschaft, DFG GA 1755/5-1 / AOBJ: 681242

Polysialic acids (polySia) are natural carbohydrate polymers of growing interest, since they interact with important players of the innate immune system, such as antimicrobial peptides and extracellular histones. Whereas in mammals only homopolymers of N-Acetylneuraminic acid are unambiguously detected, in fish a huge diversity of differently structured polySia chains is described. We want to decipher the fish polysialylation machinery and elucidate the molecular basis underlying this biochemical diversity. Based on our findings, a range of recombinant fish polysialyltransferases will be applied to generate various polysialylated proteins and surfaces with different interacting properties. The resulting sugar chains will be used as molecular anchors for immunomodulatory substances thereby regulating their activity or mediating an accumulation of bioactive polySia-carriers to hot spot of inflammation. Thus, the project opens new avenues to target key mechanisms of the immune system.