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In this study, we employed a systems biology approach to develop a dynamic model of vertebrate rod phototransduction that accounts for the details of the underlying biochemistry. Following a bottom-up strategy, we first reproduced the results of a robust model developed by Hamer et al. (Vis. Neurosci., 2005, 22(4), 417), and then added a number of additional cascade reactions including: (a) explicit reactions to simulate the interaction between the activated effector and the regulator of G-proteinsignalling (RGS); (b) a reaction for the reformation of the G-protein from separate subunits; (c) a reaction for rhodopsin (R) reconstitution from the association of the opsinapoprotein with the 11-cis-retinalchromophore; (d) reactions for the slow activation of the cascade by opsin. The extended network structure successfully reproduced a number of experimental conditions that were inaccessible to prior models. With a single set of parameters the model was able to predict qualitative and quantitative features of rod photoresponses to light stimuli ranging over five orders of magnitude, in normal and altered conditions, including genetic manipulations of the cascade components. In particular, the model reproduced the salient dynamic features of the rod from Rpe65\u2212\/\u2212 animals, a well established model for Leber congenital amaurosis and vitamin A deficiency. The results of this study suggest that a systems-level approach can help to unravel the adaptation mechanisms in normal and in disease-associated conditions on a molecular basis.<\/jats:p>\n                  <jats:p\/>","DOI":"10.1039\/b908123b","type":"journal-article","created":{"date-parts":[[2009,7,8]],"date-time":"2009-07-08T04:30:34Z","timestamp":1247027434000},"page":"1232-1246","source":"Crossref","is-referenced-by-count":45,"title":["Network-level analysis of light adaptation in rod cells under normal and altered conditions"],"prefix":"10.1093","volume":"5","author":[{"given":"Daniele","family":"Dell\u2019Orco","sequence":"first","affiliation":[{"name":"Department of Chemistry and Dulbecco Telethon Institute, University of Modena and Reggio Emilia Via Campi 183 a , 41100 Modena, Italy \u00a0 daniele.dellorco@gmail.com \u00a0 +46 46222 4543 \u00a0 +46 46222 8252"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henning","family":"Schmidt","sequence":"additional","affiliation":[{"name":"Systems Biology and Bioinformatics, University of Rostock b , Albert Einstein Str. 21, 18059 Rostock Germany \u00a0 francesca.fanelli@unimore.it \u00a0 +39 059 373543 \u00a0 +39 059 2055114"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simona","family":"Mariani","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Dulbecco Telethon Institute, University of Modena and Reggio Emilia Via Campi 183 a , 41100 Modena, Italy \u00a0 daniele.dellorco@gmail.com \u00a0 +46 46222 4543 \u00a0 +46 46222 8252"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Fanelli","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Dulbecco Telethon Institute, University of Modena and Reggio Emilia Via Campi 183 a , 41100 Modena, Italy \u00a0 daniele.dellorco@gmail.com \u00a0 +46 46222 4543 \u00a0 +46 46222 8252"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2009,7,7]]},"reference":[{"key":"2026012914033745200_cit1","doi-asserted-by":"crossref","first-page":"560","DOI":"10.1073\/pnas.93.2.560","volume":"93","author":"Baylor","year":"1996","journal-title":"Proc. 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