TroeinOstreoClock_Jan2011

Two-gene model of the Ostreococcus circadian clock

This is a model of the circadian clock of Ostreococcus tauri, with a negative feedback loop between TOC1 and CCA1 (a.k.a. LHY) and multiple light inputs. It was used and described in Troein et al., Plant Journal (2011).

The model incorporates luciferase reporters, and in this SBML model the four different versions of the model for transcriptional and translational reporter lines (pTOC1::LUC, pCCA1::LUC, TOC1-LUC and CCA1-LUC) are all accessible by setting one of the rep_X parameters to 1 and the others to 0. You can also set all four to 0 to only simulate the non-reporter core of the system.

Input to the system should be provided by modifying the "light" function. An implementation of LD 12:12 is provided as an example, but the model was also used with more complicated light regimes that vary between data sets and are not convenient to express directly in SBML.

The functions "ox_cca1" and "ox_toc1" can be altered to add overexpression of CCA1 and TOC1. Setting either to x gives additional, constitutive transcription at x times the maximal (and typically not realizable) transcription rate of the native gene. The overexpression mutant fits in Figure 7 of Troein et al. (2011) used ox_cca1 = 0.115 and oc_toc1 = 0.0584, respectively.

The functions "copies_toc1" and "copies_cca1" are normally 1 but can be lowered to simulate knockdown experiments. The functions "transcription", "translation" and "proteasome" can be modified to simulate the effects of altering the overall rate of transcription, translation and protein degradation.

The parameters were fitted specifically to data from transgenic reporter lines TOC8, pTOC3, LHY7 and pLHY7 (Corellou et al., Plant Cell 2009). Parameters that begin with "effcopies" describe the effective number of copies of CCA1 or TOC1 in the respective translational fusion lines, with anything above 1 due to the fusion proteins.

For the model fitting, the initial values were fitted to the data in the various time courses. The initial values given here correspond to the limit cycle of the system in LD 12:12. The system converges to the limit cycle in just a few days under most light conditions, so these initial values are biologically meaningful.

The species cca1luc_c and cca1luc_n have been merged into cca1luc (which corresponds to the observable luminescence signal), because Copasi refused to run the system otherwise. For TOC1-LUC, the predicted output signal is the sum of toc1luc_1 and toc1luc_2.

2011-01-07T14:21:03Z tod tod 12 2 acc_rate acc acc_rate acc 2011-01-07T14:58:29Z tod LD1212 tod t 1 0 t 2011-01-07T14:31:03Z t 0 t 2011-01-07T14:30:53Z t 1 0 t 2011-01-07T14:30:50Z t 1 0 t 2011-01-07T14:31:02Z t 0 t 2011-01-07T18:14:42Z t 1 0 t t 1 0 t 2011-01-07T18:14:40Z t T mrna translation t T mrna t D_l D_d level proteasome t light t D_l 1 light t D_d level t Di_l Di_d level light t Di_l 1 light t Di_d level 2011-01-07T18:05:12Z t R_toc1_acc acc R_toc1_cca1 cca1_n H_toc1_cca1 rep_pTOC1 L_toc1 rep_pTOC1 transcription t L_toc1 R_toc1_acc acc 1 L_toc1 R_toc1_acc acc R_toc1_cca1 cca1_n H_toc1_cca1 2011-01-07T17:27:48Z t R_toc1_acc acc R_toc1_cca1 cca1_n H_toc1_cca1 rep_TOC1 L_toc1 rep_TOC1 transcription t copies_toc1 t L_toc1 R_toc1_acc acc 1 L_toc1 R_toc1_acc acc R_toc1_cca1 cca1_n H_toc1_cca1 2011-01-07T18:04:25Z t toc1_2 R_cca1_toc1_2_l R_cca1_toc1_2_d H_cca1_toc1 rep_pCCA1 rep_pCCA1 transcription t toc1_2 light t R_cca1_toc1_2_l 1 light t R_cca1_toc1_2_d H_cca1_toc1 toc1_2 light t R_cca1_toc1_2_l 1 light t R_cca1_toc1_2_d H_cca1_toc1 1 2011-01-07T14:22:48Z t toc1_2 R_cca1_toc1_2_l R_cca1_toc1_2_d H_cca1_toc1 rep_CCA1 rep_CCA1 transcription t copies_cca1 t toc1_2 light t R_cca1_toc1_2_l 1 light t R_cca1_toc1_2_d H_cca1_toc1 toc1_2 light t R_cca1_toc1_2_l 1 light t R_cca1_toc1_2_d H_cca1_toc1 1 2011-01-07T14:29:56Z 2000-01-01T00:00:00Z reporter effcopies tf 1 reporter effcopies 1 tf acc_rate t acc_rate light t 2011-01-07T17:28:54Z R_toc1_acc acc R_toc1_cca1 H_toc1_cca1 cca1_n t L_toc1 rep_CCA1 effcopies_cca1_LHY7 transcription t ox_toc1 t copies_toc1 t L_toc1 R_toc1_acc acc 1 L_toc1 R_toc1_acc acc R_toc1_cca1 tf_output rep_CCA1 effcopies_cca1_LHY7 cca1_n H_toc1_cca1 2011-01-07T14:30:23Z t toc1_2 R_cca1_toc1_2_l R_cca1_toc1_2_d H_cca1_toc1 rep_TOC1 effcopies_toc1_TOC8 transcription t ox_cca1 t copies_cca1 t tf_output rep_TOC1 effcopies_toc1_TOC8 toc1_2 light t R_cca1_toc1_2_l 1 light t R_cca1_toc1_2_d H_cca1_toc1 tf_output rep_TOC1 effcopies_toc1_TOC8 toc1_2 light t R_cca1_toc1_2_l 1 light t R_cca1_toc1_2_d H_cca1_toc1 1 2011-01-07T14:19:06Z 2000-01-01T00:00:00Z 2011-01-07T14:53:26Z 2011-01-07T14:53:13Z 2011-01-07T14:53:15Z 2011-01-07T14:27:49Z 2011-01-07T14:19:16Z 2011-01-07T14:53:05Z 2011-01-07T14:52:33Z 2011-01-07T14:53:15Z 2011-01-07T14:53:19Z 2011-01-07T14:52:52Z 2011-01-07T14:19:25Z 2011-01-07T14:53:12Z 2011-01-07T14:53:08Z 2011-01-07T14:20:14Z 2011-01-07T18:18:41Z 2011-01-07T14:20:31Z 2011-01-07T15:03:45Z 2011-01-07T14:38:01Z 2011-01-07T14:20:18Z 2011-01-07T14:37:50Z 2011-01-07T14:37:55Z 2011-01-07T15:03:35Z 2011-01-07T14:53:48Z 2011-01-07T14:37:48Z 2011-01-07T14:53:49Z compartment function_1 acc_rate time compartment function_2 acc_rate acc 2011-01-07T17:31:40Z compartment function_3 R_toc1_acc acc R_toc1_cca1 H_toc1_cca1 cca1_n time L_toc1 parameter_4 effcopies_cca1_LHY7 2011-01-07T17:30:20Z compartment function_4 time D_toc1_2_l D_toc1_2_d toc1_2 compartment Translation time T_toc1 toc1_mrna 2011-01-07T17:30:19Z compartment function_5 time Di_toc1_12_l Di_toc1_12_d toc1_1 2011-01-07T18:15:26Z compartment D_mrna_toc1 toc1_mrna 2011-01-07T17:31:29Z compartment function_6 time toc1_2 R_cca1_toc1_2_l R_cca1_toc1_2_d H_cca1_toc1 parameter_2 effcopies_toc1_TOC8 2011-01-07T17:30:10Z compartment D_mrna_cca1 cca1_mrna compartment Translation time T_cca1 cca1_mrna 2011-01-07T18:27:53Z compartment Di_cca1_cn cca1_c 2011-01-07T14:28:08Z compartment function_4 time D_cca1_l D_cca1_d cca1_c 2011-01-07T18:15:53Z compartment function_4 time D_cca1_l D_cca1_d cca1_n 2011-01-07T17:30:16Z compartment function_7 time R_toc1_acc acc R_toc1_cca1 cca1_n H_toc1_cca1 parameter_3 L_toc1 compartment D_mrna_luc luc_mrna compartment Translation time parameter_1 luc_mrna 2011-01-07T17:30:12Z compartment D_luc luc 2011-01-07T17:30:57Z compartment function_8 time R_toc1_acc acc R_toc1_cca1 cca1_n H_toc1_cca1 parameter_2 L_toc1 2011-01-07T17:30:52Z compartment D_mrna_toc1 toc1luc_mrna 2011-01-07T17:29:17Z compartment Translation time T_toc1 toc1luc_mrna 2011-01-07T17:30:36Z compartment function_5 time Di_toc1_12_l Di_toc1_12_d toc1luc_1 2011-01-07T17:30:42Z compartment function_4 time D_toc1_2_l D_toc1_2_d toc1luc_2 2011-01-07T17:29:21Z compartment D_luc toc1luc_1 2011-01-07T17:30:31Z compartment D_luc toc1luc_2 2011-01-07T17:30:15Z compartment function_9 time toc1_2 R_cca1_toc1_2_l R_cca1_toc1_2_d H_cca1_toc1 parameter_5 2011-01-07T14:28:14Z compartment function_10 time toc1_2 R_cca1_toc1_2_l R_cca1_toc1_2_d H_cca1_toc1 parameter_4 2011-01-07T17:29:50Z compartment D_mrna_cca1 cca1luc_mrna 2011-01-07T17:30:04Z compartment Translation time T_cca1 cca1luc_mrna 2011-01-07T17:29:39Z compartment function_4 time D_cca1_l D_cca1_d cca1luc 2011-01-07T17:29:26Z compartment D_luc cca1luc