Biology subjects

Wasinger, S.

Publications and source records attributed to Wasinger, S..

2 recordsLinked to original sources

bioRxiv2026

Programming Targeted Immune Cell Migration Using Orthogonal Chemokine-Receptor Pairs

Chemokines orchestrate the migration of immune cells throughout the body, but harnessing chemokine signaling to engineer targeted cell trafficking is challenging because of their overlapping interactions and broad expression patterns. Here we used structure-guided protein design to engineer orthogonal chemokine-receptor pairs with minimal crosstalk to native systems. T cells engineered with an ortho-receptor selectively infiltrated tissues producing the ortho-chemokine, in vitro and in vivo. By engineering T cells that both sense and secrete the ortho-chemokine, we generated collective swarming behavior in which pioneer cells attract follower cells via an ortho-chemokine gradient self-organized by positive feedback. By providing orthogonal genetic control over both the generation and sensing of chemokine gradients, this system enables the construction of autonomous spatial targeting programs in engineered cells.

synthetic biology↗

bioRxiv2022

Deep learning-enabled design of synthetic orthologs of a signaling protein

Evolution-based deep generative models represent an exciting direction in understanding and designing proteins. An open question is whether such models can represent the constraints underlying specialized functions that are necessary for organismal fitness in specific biological contexts. Here, we examine the ability of three different models to produce synthetic versions of SH3 domains that can support function in a yeast stress signaling pathway. Using a select-seq assay, we show that one form of a variational autoencoder (VAE) recapitulates the functional characteristics of natural SH3 domains and classifies fungal SH3 homologs hierarchically by function and phylogeny. Locality in the latent space of the model predicts and extends the function of natural orthologs and exposes amino acid constraints distributed near and far from the SH3 ligand-binding site. The ability of deep generative models to specify orthologous function in vivo opens new avenues for probing and engineering protein function in specific cellular environments.

molecular biology↗