Deconstructing Synthetic Biology across Scales: a Conceptual Approach for Training Synthetic Biologists

by Ashty S. Karim, Dylan M. Brown, Chloé M. Archuleta, Sharisse Grannan, Ludmilla Aristilde, Yogesh Goyal, Josh N. Leonard, Niall M. Mangan, Arthur Prindle, Gabriel J. Rocklin, Keith J. Tyo, Laurie Zoloth, Michael C. Jewett, Susanna Calkins, Neha P. Kamat, Danielle Tullman-Ercek & Julius B. Lucks (Nature Communications) Synthetic biology allows us to reuse, repurpose, and reconfigure biological systems to address society’s most pressing challenges. Developing biotechnologies in this way requires integrating concepts across disciplines, posing challenges to educating students with diverse expertise. We created a framework for synthetic biology training that deconstructs biotechnologies across scales—molecular, circuit/network, cell/cell-free systems, biological communities, and societal—giving students a holistic toolkit to integrate cross-disciplinary concepts towards responsible innovation of successful biotechnologies. We present this framework, lessons learned, and inclusive teaching materials to allow its adaption to train the next generation of synthetic biologists.

To address this opportunity, we created a conceptual framework for synthetic biology training that can be used in any course or program, developed over the past several years as part of the National Science Foundation-sponsored “Synthesizing Biology Across Scales“ graduate training program at Northwestern University. The framework is based on the observation that every synthetic biology technology is made up of components that function across multiple scales—molecular, circuit/network, cell/cell-free systems, biological communities, and societal—and that the success of these technologies is deeply dependent on their interfaces (Fig. 1). This scales framework can be found in other engineering disciplines as well, such as in electrical and computer engineering where technologies naturally break down along scales, from transistors, to circuits, to chips, to devices, and integrate across scales to enable powerful applications.

A schematic representation of the deconstruction framework: biotechnologies can be deconstructed along scales to identify biological phenomena that are important to the technology at each scale, understand the principles by which these phenomena work at that scale, and identify the important interfaces between scales where engineering challenges often arise. Deconstructing technologies along scales allows multidisciplinary concepts to be mapped and applied at individual scales (annotated) and allows new technologies to be reconstructed by combining elements and applying concepts at each scale.

Here, we describe a course-based implementation of the scales framework that teaches undergraduates, masters, and PhD students how to deconstruct synthetic biology across scales, analyze how components interact at interfaces between scales to yield emergent phenomena, conceptualize how to combine components across scales to create new synthetic biology solutions to global challenges, and incorporate the consideration of ethics when developing synthetic biology technologies. Our vision is that training students to deconstruct synthetic biology technologies across scales will help them (1) recognize where their domain expertise fits within a particular synthetic biology technology, (2) identify their own knowledge gaps that can be filled through additional topical learning or research collaborations, and (3) gain a holistic picture of the landscape of pieces that must work together to create a successful technology. Each of these “science practices,” which allow students to actively engage in scientific inquiry, promotes disciplinary learning and development as a scientist25. Emphasizing the societal scale, we hope to drive responsible innovation by training students to think of concepts in ethics, access, equity, and societal-level impact early and often throughout the development of synthetic biology technologies. We envision that the scales framework and the corresponding deconstruction approach is a launching point for the field of synthetic biology to provide a foundational way of training the next generation of synthetic biologists. READ MORE