Our research focused on elucidating the role of noise, redundancy, and multivalency in glycan-mediated cell communication, with the aim of understanding fundamental principles underlying biological systems where glycans serve as a primary communication language. For this we first established a glycan-based communication model system. This served as the basis to quantify how noise and redundancy of glycan-recognition receptors during innate immune response using NFkB reporter cell lines work. More specific, we quantified glycan information decoded by individual receptors or combinations thereof, demonstrating modulation of signaling capacity by co-presentation of different glycans.
Moreover, to better understand the reading process of the message encoded in cell surface glycans we advanced single-particle tracking by developing a biophysical method to investigate real-time glycan-receptor recognition dynamics using microscopy. This led to tracked glycan nanoparticles using deep learning methods, revealing insights into receptor engagement dynamics and endolysosomal sorting processes.
Furthermore, we initiated the characterization of glycome heterogeneity on a single level. The heterogeneity of glycans displayed on individual cells is unchartered ground and using machine learning algorithms and lectin probes we paved the way for future research in this direction since glycome variation contributes to cell fate determination, signaling, and communication at single-cell level.
From a methodological standpoint, out work led to several innovative findings. We applied information theory to evaluate cellular signaling at the single-cell level, providing guidelines for computation of channel capacity. Next, our approach for tracking nanoparticles within cells, enhancing tracking accuracy will help understanding the decoding mechanism using machine learning-based tracking methods. Finally, on a biological level, we identified dectin-2 as a "noisy lectin" with implications for host-pathogen interactions and immune response modulation. The advanced understanding of multivalent interactions, receptor diffusivity, and endocytosis dynamics in glycan-lectin interactions, has potential applications in targeted drug delivery and vaccine design.
