The overarching goal of the Biohybrid Systems Lab is to elucidate (1) how biological systems coordinate the hierarchical structures and functions of their individual components in order to produce emergent behaviors and (2) how disrupting this coordination potentiates disease.
To pursue this goal, we design, build, and test a hierarchy of engineered biological systems capable of reproducing the targeted emergent behaviors of their natural counterparts, by reconstructing the interactions between components and the interplay between components and the environment. The primary focus is to recapitulate (1) biomechanical dynamic interactions between bio-components (e.g. the cytoskeleton and the lipid membrane, cell-cell couplings) and (2) tissue- and organ-level coordinated conduction and contraction of the muscle tissues. The lessons learned from studying these primary systems are applicable to modeling other biological systems and organ systems. Importantly, these systems are prey to many diseases, and modeling them helps to identify pathogenic mechanisms and new therapeutic targets. Despite recent progress in modeling these systems, however, engineered systems still do not demonstrate the complexity and robustness of natural systems.
To overcome this gap in current models, we are refining engineered biological systems by (scale) identifying the minimum structural and functional unit needed to replicate targeted structures and functions at spatiotemporal scales while also minimizing complexity for better reproducibility; (control) integrating regulatory mechanisms to control structural organization and the activities of components at specific spatiotemporal scales; and (readouts) employing quantitative methods to capture component- and system-level structural organization and activities that can be linked to emergent behaviors. In concert with system construction, we are developing biohybrid fabrication methods and measurement systems that enable replication of hierarchical structures and improve the biotic-abiotic interface.
Constructing these systems provides insights into the mechanisms behind emergent behaviors. These scientific discoveries and technical developments will be directly translated into clinical and industrial applications. The engineered biological systems, integrated with stem cell and gene-editing technologies, provide quantitative assessment platforms for disease diagnosis and potentially accelerate therapeutic development pipelines for personalized medicine. We are also seeking to create biological autonomous systems capable of orchestrating adaptive behaviors through the combined applications of microfabrication, electronics, close-looped control, biomaterials, and tissue engineering.