Periodic Reporting for period 3 - GLYCONOISE (Emergent properties of cell surface glycosylation in cell-cell communication)
Reporting period: 2020-02-01 to 2020-08-31
How can such a specially and temporally regulated, complex and stochastic system encode reliable for information that can successfully be decoded by other cells through the use of lectin receptors? Here we address the fundaments of how cell surface exposed sugars in multicellular organisms serve as information storage and how they are decoded. For this we treat this system like a communication channel in which a sender cell conveys a defined message to a receiver cell. This formalism opens the door for cross-disciplinary approaches coming from theoretical physics (i.e. information theory) to aid the analysis of the biological data. A central figure in any communication channel is noise and we will assess the different layers of noise and dissect their origin and influence. We combine insights from atomic resolution understanding the biophysics of protein glycan interaction with experimental assessment of cellular mechanisms addressing these questions: How often does a protein-carbohydrate interaction on a cell surface lead to a productive, biological response? How do lectins and glycans find each other on two-dimensional surfaces? How much information can be transferred through such a communication channel and how does this compare to glycan-independent pathways of cell-cell communication?
Taken together these insights will help us to understand why almost all tumor cells change their cell surface glycans in a similar way. Moreover, we gain insight into fundamental processes in biology that lead to better understanding of how glycosylation became such an essential posttranslational modification present in every living organism. Furthermore, nature uses sugar for specific delivery of cargo to certain cells in the body and with our knowledge on how such system works, we can address molecular drug targeting strategies more efficiently to reduce side effects of novel therapeutics. Finally, our insights might stimulate the design of novel communication channels based on heteromultivalent low affinity interactions.
Moreover, an approach has been developed, which allows us to investigate several hundred incoming particles on the cell surface during single particle tracking analysis. In such a high density of particles, an analysis was impossible. With our technology, including newly developed code, particle fusion and splitting can be monitored in terabytes of life cell imaging data.
We are also addressing the problem of single cell glycome analysis. Important key experiments have been performed and we are now approaching a solution of this longstanding problem in glycobiology in the remaining funding period.