Engineering plasmid copy number heterogeneity for dynamic microbial adaptation.

Natural microbial populations exploit phenotypic heterogeneity for survival and adaptation. However, in engineering biology, limiting the sources of variability is a major focus. Here we show that intentionally coupling distinct plasmids via shared replication mechanisms enables bacterial populations to adapt to their environment.

Phenotypic Patterning through Copy Number Adaptation to Environmental Gradients.

We recently described a paradigm for engineering bacterial adaptation using plasmids coupled to the same origin of replication. In this study, we use plasmid coupling to generate spatially separated and phenotypically distinct populations in response to heterogeneous environments. Using a custom microfluidic device, we continuously tracked engineered populations along induced gradients, enabling an in-depth analysis of the spatiotemporal dynamics of plasmid coupling.

Engineered bacteria detect tumor DNA.

Synthetic biology has developed sophisticated cellular biosensors to detect and respond to human disease. However, biosensors have not yet been engineered to detect specific extracellular DNA sequences and mutations. Here, we engineered naturally competent to detect donor DNA from the genomes of colorectal cancer (CRC) cells, organoids, and tumors.

Stability, robustness, and containment: preparing synthetic biology for real-world deployment.

As engineered microbes are used in increasingly diverse applications across human health and bioproduction, the field of synthetic biology will need to focus on strategies that stabilize and contain the function of these populations within target environments. To this end, recent advancements have created layered sensing circuits that can compute cell survival, genetic contexts that are less susceptible to mutation, burden, and resource control circuits, and methods for population variability reduction. These tools expand the potential for real-world deployment of complex microbial systems by enhancing their environmental robustness and functional stability in the face of unpredictable host response and evolutionary pressure.

Wall stresses of early remodeled pulmonary autografts.

Objective: The Ross procedure is an excellent option for children or young adults who need aortic valve replacement because it can restore survival to that of the normal aged-matched population. However, autograft remodeling can lead to aneurysmal formation and reoperation, and the biomechanics of this process is unknown. This study investigated postoperative autograft remodeling after the Ross procedure by examining patient-specific autograft wall stresses.

Regional biomechanical and failure properties of healthy human ascending aorta and root.

Purpose: Aortic dissection (AD) is a life-threatening event that occurs when the intimal entry tear propagates and separates inner from outer layers of the aorta. Diameter, the current criterion for aneurysm repair, is far from ideal and additional evidence to optimize clinical decision would be extremely beneficial. Biomechanical investigation of the regional failure properties of aortic tissue is essential to understand and proactively prevent AD.