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Biology subjects

Ho, M. H.

Publications and source records attributed to Ho, M. H..

2 recordsLinked to original sources

Visual-spatial dynamics drive adaptive social learning in immersive environments

Human cognition is distinguished by our ability to adapt to different environments and circumstances. Yet the mechanisms driving adaptive behavior have predominantly been studied in separate asocial and social contexts, with an integrated framework remaining elusive. Here, we use a collective foraging task in a virtual Minecraft environment to integrate these two fields, by leveraging automated transcriptions of visual field data combined with high-resolution spatial trajectories. Our behavioral analyses capture both the structure and temporal dynamics of social interactions, which are then directly tested using computational models sequentially predicting each foraging decision. These results reveal that adaptation mechanisms of both asocial foraging and selective social learning are driven by individual foraging success (rather than social factors). Furthermore, it is the degree of adaptivity--of both asocial and social learning--that best predicts individual performance. These findings not only integrate theories across asocial and social domains, but also provide key insights into the adaptability of human decision-making in complex and dynamic social landscapes.

animal behavior and cognition↗

Rapid generation of potent antibodies by autonomous hypermutation in yeast

The predominant approach for antibody generation remains animal immunization, which can yield exceptionally selective and potent antibody clones owing to the powerful evolutionary process of somatic hypermutation. However, animal immunization is inherently slow, has poor compatibility with certain antigens (e.g., integral membrane proteins), and suffers from self-tolerance and immunodominance, which limit the functional spectrum of antibodies that can be obtained. Here, we describe Autonomous Hypermutation yEast surfAce Display (AHEAD), a synthetic recombinant antibody generation technology that imitates somatic hypermutation inside engineered yeast. In AHEAD, antibody fragments are encoded on an error-prone orthogonal DNA replication system, resulting in Saccharomyces cerevisiae populations that continuously mutate surface-displayed antibody repertoires. Simple cycles of yeast culturing and enrichment for antigen binding drive the evolution of high-affinity antibody clones in a readily parallelizable process that takes as little as 2 weeks. We applied AHEAD to generate nanobodies against the SARS-CoV-2 S glycoprotein, a GPCR, and other targets. The SARS-CoV-2 nanobodies, concurrently evolved from an open-source naive nanobody library in 8 independent experiments, reached subnanomolar affinities through the sequential fixation of multiple mutations over 3-8 AHEAD cycles that saw [~]580-fold and [~]925-fold improvements in binding affinities and pseudovirus neutralization potencies, respectively. These experiments highlight the defining speed, parallelizability, and effectiveness of AHEAD and provide a template for streamlined antibody generation at large with salient utility in rapid response to current and future viral outbreaks.

bioengineering↗