RESEARCH HIGHLIGHTS

GENE REGULATION Infiltrating the network

An inventive approach to the engineer- extended the longevity of these . ing of gene expression networks rep- By modifying the transcription units so resents an important step in modeling that the transcription factors could regu- such complex processes as embryonic late each other’s expression (for instance, formation. expression of gene A represses expression Embryonic patterning is vital to the of genes B and C) and reducing protein developmental process, and anybody half-life by adding proteases to the cham- methods who has studied developmental ber, the patterns were considerably sharp- is aware of the byzantine temporal and ened. A , designed as spatial regulatory processes involved, a companion to the in vitro system, closely with extensive genetic cross-talk and mul- mirrored the patterns they observed under .com/nature e tiple gradients of expression interacting various experimental conditions. with each other to establish boundaries The authors found that this system .natur

w where other expression events can take effectively illustrated several key prin- place. Modeling these systems is essen- ciples of pattern formation, including the tial to deciphering them, according to importance of cross-repression. Boston

http://ww Mark Isalan, an investigator in the lab of University researcher James Collins, whose

Luis Serrano at the European Molecular own work has dealt extensively with genet-

oup Biology Laboratory (EMBL). “You’ve got ic networks, expressed admiration for this r

G all these beautiful networks,” he says, “but technique: “I think that the [focus of this]

maybe the limit of whether you under- field, going forward, is not going to be cre- stand them is whether you can rebuild ating novel circuits with useful functions lishing them from first principles.” in biotechnology, but more… designing b Isalan’s team recently demonstrated a isolated circuits with particular designs Pu new breakthrough on this front, assem- to explore natural biological phenomena bling an artificial gene network that rep- underlying gene expression and in cel- Nature

licates some key processes of Drosophila lular function. And in this case, I think 5 pattern formation (Isalan et al., [Serrano’s team] did a really nice job.”

200 2005a). They designed several bead-con- Although these in vitro studies have

© jugated transcription units using a tech- yielded interesting results, Isalan’s real nique for the linkage of expression-ready hope is to promptly move this system into PCR products to magnetic beads, with cell-based studies, using a related tech- each unit containing a T7 or SP6 promoter nique described by his group in another and a gene encoding one of three different recent paper (Isalan et al., 2005b). “I think synthetic transcription factors. it will be much more relevant to try and To simulate the early-stage Drosophila engineer networks in multicellular sys- embryo, Isalan’s group magnetically tems,” he says, “and you can use this as arranged their beads into discrete zones in a tool to program individual cells to do a chamber filled with low–melting point things in space, and make more physiolog- agarose, permitting the passive diffusion ically relevant systems.” In the meantime, of transcription factors. The arrangement however, he hopes that this will demon- was designed to spatially restrict expres- strate some of the potential applications sion for each to dif- of his team’s magnetic bead–based strat- ferent regions of the ‘embryo’, in a manner egy. “I hope that people might try playing that roughly mirrors normal expression with it, because it’s quite a neat little tool of the developmental genes hunchback, to localize genes in particular places, and giant and Krüppel. In initial experiments, I think you can do a lot with it.” the only other restriction on the range of Michael Eisenstein

expression resulted from the distribution RESEARCH PAPERS of T7 and SP6 RNA polymerases and dif- Isalan, M. et al. Engineering gene networks to fusion within the chamber. This resulted emulate Drosophila embryonic pattern formation. in the of some crude patterns; PLoS Biol. 3, 1–9 (2005a). Isalan, M. et al. Localized transfection on arrays however, the addition of further layers of of magnetic beads coated with PCR products. Nat. regulation considerably sharpened and Methods 2, 113–118 (2005b).

246 | VOL.2 NO.4 | APRIL 2005 | NATURE METHODS