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Theses Doctoral

Understanding and Engineering Multicomponent Living Systems: Examples from Synthetic Genomics and Engineered Living Materials

McBee, Andrew Ross MacKay

Much of Nature is composed of highly modular and composable nested multicomponent living systems. Synthetic biology and bioengineering exploit this modularity to understand and engineer living things. This thesis explores two projects coupled by these principles, the first utilizing a synthetic genomics approach to probe the evolutionary history, flexibility, and modularity of core metabolism, and the second adapting and engineering components of a living material to generate living architecture and embed add program new behaviors into the living biocomposite.

Chapter 1 details the synthetic resurrection of a core metabolic pathway lost from the metazoan lineage millions of years ago. All metazoans are auxotrophic for 9 of the 20 amino acids, the so-called “essential” amino acids. The pressures behind the loss of the 9 are a deep evolutionary puzzle. To investigate this event and probe the limits of core metabolic flexibility, we generated a synthetic valine prototrophic mammalian cell line, restoring valine self-sufficiency to the metazoan lineage. The restoration of this pathway implies the modern mammalian metabolism is still compatible with autogenous valine production, suggests profound modularity in core metabolism, and underscores the potential usefulness of large-scale synthetic genomics approaches in a answering deep evolutionary questions.

Chapter 2 describes the engineering of a hybrid fungal-bacterial biocomposite by adapting and leveraging existing behaviors and microbial constituents of a living material. Fungal biocomposites are composed of a particulate lignocellulosic feedstock bound together into a bulk biocomposite by a network of dense fungal mycelium. Using a bioprospecting approach, we designed architectural and design strategies that relied on the natural substrate flexibility and growth patterns of the fungal component of the biocomposite to form origami-inspired human scale folding structures. Similarly, we isolated, characterized, and engineered a natural microbial component of the biocomposite’s own microbiome and used its pre-adapted ability to engraft in the growing biomaterial to embed new genetic functionalities in biocomposite objects. We believe that the strategy of bioprospecting useful components and behaviors holds promise for the development of future biomaterials adapted from living systems.

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More About This Work

Academic Units
Biological Sciences
Thesis Advisors
Wang, Harris H.
Cornish, Virginia W.
Degree
Ph.D., Columbia University
Published Here
November 17, 2021