Design-driven, multi-use research agendas to enable applied synthetic biology for global health

Abstract

Many of the synthetic biological devices, pathways and systems that can be engineered are multi-use, in the sense that they could be used both for commercially-important applications and to help meet global health needs. The on-going development of models and simulation tools for assembling component parts into functionally-complex devices and systems will enable successful engineering with much less trial-and-error experimentation and laboratory infrastructure. As illustrations, I draw upon recent examples from my own work and the broader Keasling research group at the University of California Berkeley and the Joint BioEnergy Institute, of which I was formerly a part. By combining multi-use synthetic biology research agendas with advanced computer-aided design tool creation, it may be possible to more rapidly engineer safe and effective synthetic biology technologies that help address a wide range of global health problems.

Keywords: Computer-aided design; Model-driven design and engineering.

Fig. 1

Eschericia coli platform for p-aminostyrene production. Many synthetic biological devices, pathways and systems have multi-use potential; they can be used to produce both industrially-relevant compounds and low cost materials for global health. As shown, metabolic pathways constructed to produce industrially-relevant aromatics (p-aminostryene, p-AS) could be reengineered to producelow cost drugs, such as painkillers (opiate analgesics), experimental type II diabetes treatments (dipeptidyl peptidase IV inhibitors) and antibiotics (pristinamycin antibiotics). Gene products and molecule names are as described (Carothers et al. 2011)

Fig. 2

Design-driven RNA device engineering. We formulated a model-driven approach for engineering RNA-based genetic control devices to program pathway and circuit gene expression, with a 94 % correlation observed between the predicted and measured outputs. This approach could be used to engineer sets of static and dynamic RNA devices and implement novel designs derived from systems-level models (after Carothers et al. 2011). More broadly, this work established generalizable frameworks for integrating biochemical and biophysical modeling and developing biological CAD tools that reduce the time and resources needed to engineer functionally-complex devices, pathways and systems

Fig. 3

RNA-regulated expression devices as biosensors. Aptazyme-regulated expression devices (aREDs) (Carothers et al. 2011) could be designed for dessicated (Billi et al. 2000) engineered biosensor hosts to function as point-of-care diagnostics that produce genetically-encoded outputs upon detecting target compounds, such as pathogen biosensors or nutritional states

Fig. 4

Applied synthetic biology for global health. Research agendas should target biosynthetic and biosensor platforms with multi-use potential, as identified by market research and analysis of global health priorities. Researchers in scientifically-advanced nations could perform initial system design and experimentation, with industrially-relevant materials produced following device, pathway and system optimization focused on commercial development. Device, pathway and system reengineering for applications in global health could then be carried out in collaboration with scientists in lower-resource countries and the DIY-bio community