Synthetic biology is revolutionizing how we conceptualize and approach the
engineering of biological systems. Recent advances in the field are
allowing us to expand beyond the construction and analysis of small gene
networks towards the implementation of complex multicellular systems with a
variety of applications. In this talk I will describe our integrated
computational/experimental approach to engineering complex behavior in
living systems ranging from bacteria to stem cells. In our research, we
appropriate useful design principles from electrical engineering and other
well established fields. These principles include abstraction,
standardization, modularity, and computer aided design. But we also spend
considerable effort towards understanding what makes synthetic biology
different from all other existing engineering disciplines and discovering
new design and construction rules that are effective for this unique
discipline.
We will briefly describe the implementation of genetic circuits with
finely-tuned digital and analog behavior and the use of artificial
cell-cell communication to coordinate the behavior of cell populations for
programmed pattern formation. Arguably the most significant contribution
of synthetic biology will be in medical applications such as tissue
engineering. We will discuss preliminary experimental results for
obtaining precise spatiotemporal control over stem cell differentiation.
For this purpose, we couple elements for gene regulation, cell fate
determination, signal processing, and artificial cell-cell communication.
Towards this goal, we have implemented two types of mammalian communication
systems, one that uses bacterial quorum sensing enzymes and response
elements and one that is based on the secretion and endocytosis of
transcription factors. We will conclude by discussing the design and
preliminary results for creating an artificial tissue homeostasis system
where genetically engineered stem cells maintain indefinitely a desired
level of pancreatic beta cells despite attacks by the autoimmune response.
The system, which relies on artificial cell-cell communication, various
regulatory network motifs, and programmed differentiation into beta cells,
may one day be useful for the treatment (or cure) of diabetes.
Selected publications:
Basu S, Gerchman Y, Collins CH, Arnold FH, Weiss R (2005) A synthetic
multicellular system for programmed pattern formation. Nature 434 p1130-4
Andrianantoandro E, Basu S, Karig DK, Weiss R (2006) Synthetic biology: new
engineering rules for an emerging discipline. Molecular Systems Biology
Rinaudo K, Bleris L, Maddamsetti R, Subramanian S, Weiss R, Benenson Y
(2007) A universal RNAi-based logic evaluator that operates in mammalian
cells. Nature Biotechnology
