of evolutionary stability, population synchronization, and the constraints inherent in complex metabolic pathways. In addition, problems inherent to all synthetic biology projects, such as uncertainty about the effects of a synthetic circuit on host growth rate, or uncertainty in biochemical parameters, could be even more challenging in the polyculture context.
Here we will discuss the key issues, opportunities, and challenges that we will face in efforts to make use of the “parallelism” inherent in polyculture systems.
How can one engineer self-synchronizing populations, that behave coherently, despite cell-cell variability?
How do we achieve effective cell communication over multiple length and time scales. For example, what are strategies for cell communication to nearest neighbors, over several cell layers and across an entire culture? How do we design cells to self-organize into defined three-dimensional structures (Example: organs). Temporally, how do we synchronize cell cycles or metabolic states?
What kinds of metabolic processes are best carried out through the cooperative action of distinct strains, rather than consolidated in a single cell? Are there advantages to spreading out metabolic functions even when the individual pathways involved are chemically compatible with each other? (Example: Chris Voigt’s research, www.voigtlab.ucsf.edu.)
What are optimal strategies for engineering ecological systems that maintain programmable population fractions? How can such a system be made ecologically and evolutionarily stable (i.e., robust to invasion by “cheaters”)? (Example: Alexander van Oudenaarden’s research, http://web.mit.edu/biophysics; and Wenying Shou’s COSMO, see reading reference below.) What applications might exist for controlled multi-population systems?
Trojan horses: How do we engineer organisms that can invade and flourish in natural populations while altering the behavior of the affected organism/ecosystem in a controlled and desirable manner? (Example: Bruce Hay’s work on making elements that invade and spread through mosquito populations while making them resistant to malaria, www.its.caltech.edu/~haylab.)