for control of biological function. Such tools will become increasingly important as synthetic biology embraces more fully the design of complex multicellular systems.

• What are the most promising approaches to chemical and physical control of biological function? Inhibition or re-wiring of cellular pathways? Introduction of light-sensitive or mechanically-sensitive components? Others?

• Which cellular pathways are most promising with respect to control by chemical and physical means?

• What advantages might accrue from the development of novel chemical substrates (e.g., “abiological” nucleotides, amino acids, sugars, and other biosynthetic intermediates) for use in synthetic biology?

• Can we create organisms that prefer or even require altered sets of molecular substrates? If so, what kinds of biological behavior might emerge from such adaptations?

• To what extent can we change the properties of biological macromolecules? Will such changes allow us to overcome some of the most important limitations of macromolecular therapeutics or industrial enzymes (e.g., sensitivity to proteases, surfactants, or dehydration)?

• How can control of spatial relationships among cells contribute to the engineering of novel biological function?

• Are there advances in bioreactor design and micro- and nano-fluidic technologies that should be brought to bear on problems in synthetic biology?

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Justman QA, Serber Z, Ferrel Jr. JE, El-Samad H, Shokat KM. Tuning the activation threshold of a kinase network by nested feedback loops. Science 2009;324:509: http://www.sciencemag.org/cgi/content/full/324/5926/509. Accessed online 28 July 2009.