A bottom-up approach to gene regulation. Export

@article{citeulike:506455, abstract = {The ability to construct synthetic gene networks enables experimental investigations of deliberately simplified systems that can be compared to qualitative and quantitative models. If simple, well-characterized modules can be coupled together into more complex networks with behaviour that can be predicted from that of the individual components, we may begin to build an understanding of cellular regulatory processes from the 'bottom up'. Here we have engineered a promoter to allow simultaneous repression and activation of gene expression in Escherichia coli. We studied its behaviour in synthetic gene networks under increasingly complex conditions: unregulated, repressed, activated, and simultaneously repressed and activated. We develop a stochastic model that quantitatively captures the means and distributions of the expression from the engineered promoter of this modular system, and show that the model can be extended and used to accurately predict the in vivo behaviour of the network when it is expanded to include positive feedback. The model also reveals the counterintuitive prediction that noise in protein expression levels can increase upon arrest of cell growth and division, which we confirm experimentally. This work shows that the properties of regulatory subsystems can be used to predict the behaviour of larger, more complex regulatory networks, and that this bottom-up approach can provide insights into gene regulation.}, author = {Guido, Nicholas J. and Wang, Xiao and Adalsteinsson, David and McMillen, David and Hasty, Jeff and Cantor, Charles R. and Elston, Timothy C. and Collins, J. J.}, citeulike-article-id = {506455}, citeulike-linkout-0 = {http://dx.doi.org/10.1038/nature04473}, citeulike-linkout-1 = {http://dx.doi.org/10.1038/nature04473}, citeulike-linkout-2 = {http://view.ncbi.nlm.nih.gov/pubmed/16482159}, citeulike-linkout-3 = {http://www.hubmed.org/display.cgi?uids=16482159}, day = {16}, doi = {10.1038/nature04473}, issn = {1476-4687}, journal = {Nature}, keywords = {modelling, synthetic\_biology}, month = {February}, number = {7078}, pages = {856--860}, posted-at = {2006-10-05 09:14:55}, priority = {2}, title = {A bottom-up approach to gene regulation.}, url = {http://dx.doi.org/10.1038/nature04473}, volume = {439}, year = {2006} }

TY - JOUR ID - citeulike:506455 L3 - citeulike-article-id:506455 N2 - The ability to construct synthetic gene networks enables experimental investigations of deliberately simplified systems that can be compared to qualitative and quantitative models. If simple, well-characterized modules can be coupled together into more complex networks with behaviour that can be predicted from that of the individual components, we may begin to build an understanding of cellular regulatory processes from the 'bottom up'. Here we have engineered a promoter to allow simultaneous repression and activation of gene expression in Escherichia coli. We studied its behaviour in synthetic gene networks under increasingly complex conditions: unregulated, repressed, activated, and simultaneously repressed and activated. We develop a stochastic model that quantitatively captures the means and distributions of the expression from the engineered promoter of this modular system, and show that the model can be extended and used to accurately predict the in vivo behaviour of the network when it is expanded to include positive feedback. The model also reveals the counterintuitive prediction that noise in protein expression levels can increase upon arrest of cell growth and division, which we confirm experimentally. This work shows that the properties of regulatory subsystems can be used to predict the behaviour of larger, more complex regulatory networks, and that this bottom-up approach can provide insights into gene regulation. IS - 7078 JF - Nature SN - 1476-4687 EP - 860 TI - A bottom-up approach to gene regulation. VL - 439 SP - 856 KW - modelling KW - synthetic_biology AU - Guido, Nicholas AU - Wang, Xiao AU - Adalsteinsson, David AU - McMillen, David AU - Hasty, Jeff AU - Cantor, Charles AU - Elston, Timothy AU - Collins, JJ PY - 2006/02/16/ UR - http://dx.doi.org/10.1038/nature04473 ER -