Biology subjects

Kiessling, L.

Publications and source records attributed to Kiessling, L..

3 recordsLinked to original sources

bioRxiv2026

Identification of Direct and Network-Mediated Activation of Retinal Ganglion Cells from Visually Evoked Potentials Using Machine Learning

ObjectiveTo preserve the encoding of visual information in prosthetic vision as close to natural as possible, subretinal photovoltaic implants, which replace the lost photoreceptors, strive to stimulate the second-order retinal neurons, the bipolar cells, while avoiding direct activation of the downstream retinal ganglion cells. To assess the range of such selective subretinal activation, we implanted the devices in rodent models of retinal degeneration and measured the stimulation thresholds based on the visually evoked potentials. After assessment of the bipolar cell-mediated thresholds, direct activation of retinal ganglion cells was measured following intraocular injection of synaptic blockers. Since these chemicals are toxic to the retina, this procedure can only be done once in each animal. ApproachWe developed a machine-learning model that identifies the stimulation pathway directly from the recorded visually evoked potentials, eliminating the need for synaptic blockers. The model was trained on recordings from rats implanted with PRIMA subretinal arrays and evaluated on two additional implant architectures, a second rat species, and a different anesthesia protocol. Main ResultsThe classifier achieved a balanced accuracy of 92% in cross-validation on the training data. Generalization to all unseen experimental conditions yielded an average balanced accuracy of 91%. Integrated Gradients analysis showed that combined bipolar and ganglion cell responses were driven by the early P1 component, while bipolar cell responses relied on later waveform components, consistent with thalamocortical processing dynamics. SignificanceThe described computational alternative to pharmacological blockers should improve the experimental throughput, allow multiple recordings over the lifetime of the same animal, and might be applicable to optimization of the stimulation settings in patients.

bioengineering↗

bioRxiv2026

Single-Cell and Spatial Methods for Multimodal Functional Glycan Profiling in Tissues

Glycans regulate multiple physiological processes, including immune recognition and cancer progression. In disease, altered glycan landscapes are interpreted by human lectins. Functional glycan-lectin interactions are difficult to profile because glycans are not genome-encoded and their changes are poorly captured by existing multimodal methods. We present two platforms, single-cell outlining and transcriptome sequencing (scGOAT-seq) and GlycoScope, which use human lectins to enable functional glycan accessibility into single-cell and spatial multiomic measurements. ScGOAT-seq quantifies lectin-accessible glycan states with gene expression, while GlycoScope enables multiplexed in situ co-detection of glycans and proteins in tissues. Applying these approaches to immune cells, we identify stimulus-specific glycan remodeling and show that distinct Siglec-ligand-defined programs stratify immune activation states not captured by traditional methods; in follicular lymphoma, GlycoScope, resolves spatial glycan programs associated with malignant B cells and localized immune microenvironments. The presented methods provide a general framework for integrating functional glycan accessibility into single-cell and spatial multiomics.

molecular biology↗

bioRxiv2019

Antigen structure affects cellular routing through DC-SIGN

Dendritic cell (DC) lectins mediate the recognition, uptake, and processing of antigens, but they can also be co-opted by pathogens for infection. These distinct activities depend upon the routing of antigens within the cell. Antigens directed to endosomal compartments are degraded and the peptides presented on MHC class II molecules thereby promoting immunity. Alternatively, HIV-1 can avoid degradation, as virus engagement with C-type lectin receptors (CLRs), such as DC-SIGN, results in trafficking to surface-accessible invaginated pockets. This process appears to enable infection of T cells in trans. We sought to explore whether antigen fate upon CLR-mediated internalization was affected by antigen physical properties. To this end, we employed the ring-opening metathesis polymerization to generate glycopolymers that each display multiple copies of mannoside ligand for DC-SIGN yet differ in length and size. The rate and extent of glycopolymer internalization depended upon polymer structure--longer polymers were internalized more rapidly and more efficiently than were shorter polymers. The trafficking, however, did not differ, and both short and longer polymers colocalized with transferrin-labeled early endosomes. To explore how DC-SIGN directs larger particles, such as pathogens, we induced aggregation of the polymers to access particulate antigens. Strikingly, these particulate antigens were diverted to the invaginated pockets that harbor HIV-1. Thus, antigen structure has a dramatic effect on DC-SIGN-mediated uptake and trafficking. These findings have consequences for the design of synthetic vaccines. Additionally, the results suggest new strategies for targeting DC reservoirs that harbor viral pathogens.\n\nSignificance StatementDendritic cells (DCs) express cell-surface proteins (lectins) that bind to carbohydrates displayed on the surface of pathogens. The binding of pathogens to these lectins results in internalization to endosomal compartments where the pathogens are destroyed and an immune response is initiated. HIV-1 can subvert this process - lectin engagement routes HIV-1 to cellular compartments that allow the virus to evade destruction. We synthesized glycopolymers to test whether the size and physical properties of the antigens impact trafficking. Small polymers trafficked to endosomes, as expected. Alternatively, large particulate polymers localized in the non-endosomal compartments occupied by HIV. These data indicate that antigen structure affects routing by DC lectins. Our findings can be exploited to direct cargo to different compartments.

immunology↗