Dataset Information

Ray2013 - Meiotic initiation in S. cerevisiae

ABSTRACT: Ray2013 - Meiotic initiation in S. cerevisiae A mathematical representation of early meiotic events, particularly feedback mechanisms at the system level and phosphorylation of signalling molecules for regulating protein activities, is described here This model is described in the article: Dynamic modeling of yeast meiotic initiation. Ray D, Su Y, Ye P. BMC Syst Biol. 2013 May 1;7:37 Abstract: BACKGROUND: Meiosis is the sexual reproduction process common to eukaryotes. The diploid yeast Saccharomyces cerevisiae undergoes meiosis in sporulation medium to form four haploid spores. Initiation of the process is tightly controlled by intricate networks of positive and negative feedback loops. Intriguingly, expression of early meiotic proteins occurs within a narrow time window. Further, sporulation efficiency is strikingly different for yeast strains with distinct mutations or genetic backgrounds. To investigate signal transduction pathways that regulate transient protein expression and sporulation efficiency, we develop a mathematical model using ordinary differential equations. The model describes early meiotic events, particularly feedback mechanisms at the system level and phosphorylation of signaling molecules for regulating protein activities. RESULTS: The mathematical model is capable of simulating the orderly and transient dynamics of meiotic proteins including Ime1, the master regulator of meiotic initiation, and Ime2, a kinase encoded by an early gene. The model is validated by quantitative sporulation phenotypes of single-gene knockouts. Thus, we can use the model to make novel predictions on the cooperation between proteins in the signaling pathway. Virtual perturbations on feedback loops suggest that both positive and negative feedback loops are required to terminate expression of early meiotic proteins. Bifurcation analyses on feedback loops indicate that multiple feedback loops are coordinated to modulate sporulation efficiency. In particular, positive auto-regulation of Ime2 produces a bistable system with a normal meiotic state and a more efficient meiotic state. CONCLUSIONS: By systematically scanning through feedback loops in the mathematical model, we demonstrate that, in yeast, the decisions to terminate protein expression and to sporulate at different efficiencies stem from feedback signals toward the master regulator Ime1 and the early meiotic protein Ime2. We argue that the architecture of meiotic initiation pathway generates a robust mechanism that assures a rapid and complete transition into meiosis. This type of systems-level regulation is a commonly used mechanism controlling developmental programs in yeast and other organisms. Our mathematical model uncovers key regulations that can be manipulated to enhance sporulation efficiency, an important first step in the development of new strategies for producing gametes with high quality and quantity. This model is hosted on BioModels Database and identified by: BIOMD0000000626 . To cite BioModels Database, please use: BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models . To the extent possible under law, all copyright and related or neighbouring rights to this encoded model have been dedicated to the public domain worldwide. Please refer to CC0 Public Domain Dedication for more information.

OTHER RELATED OMICS DATASETS IN: PRJNA93891PRJNA149975

SUBMITTER: Debjit Ray

PROVIDER: BIOMD0000000626 | BioModels | 2024-09-02

REPOSITORIES: BioModels

ACCESS DATA

Dataset's files

Source:

			Action	DRS
	BIOMD0000000626?filename=BIOMD0000000626-biopax2.owl	Owl
	BIOMD0000000626?filename=BIOMD0000000626-biopax3.owl	Owl
	BIOMD0000000626?filename=BIOMD0000000626-matlab.m	Other
	BIOMD0000000626?filename=BIOMD0000000626-octave.m	Other
	BIOMD0000000626?filename=BIOMD0000000626.m	Other

Items per page:

1 - 5 of 16

Publications

Dynamic modeling of yeast meiotic initiation.

Ray Debjit D Su Yongchun Y Ye Ping P

BMC systems biology 20130501

<h4>Background</h4>Meiosis is the sexual reproduction process common to eukaryotes. The diploid yeast Saccharomyces cerevisiae undergoes meiosis in sporulation medium to form four haploid spores. Initiation of the process is tightly controlled by intricate networks of positive and negative feedback loops. Intriguingly, expression of early meiotic proteins occurs within a narrow time window. Further, sporulation efficiency is strikingly different for yeast strains with distinct mutations or genet ...[more]

PMID: 23631506

Publication: 1/11

Similar Datasets

Project description:Novak1993 - Cell cycle M-phase control The model reproduces Figure 9 of the paper. Please note that active MPF and cyclin concentrations in the paper are given relative to total cdc2 concentration (100nM). Active MPF (dimer_p) is the cyclin-cdc2 complex that is phosphorylated at Thr161. The earlier versions of the model was successfully tested on MathSBML and Jarnac, and the current version was checked in Copasi. This model is described in the article: Numerical analysis of a comprehensive model of M-phase control in Xenopus oocyte extracts and intact embryos. Novak B, Tyson JJ. J. Cell. Sci. 1993 Dec; 106 ( Pt 4): 1153-1168 Abstract: To contribute to a deeper understanding of M-phase control in eukaryotic cells, we have constructed a model based on the biochemistry of M-phase promoting factor (MPF) in Xenopus oocyte extracts, where there is evidence for two positive feedback loops (MPF stimulates its own production by activating Cdc25 and inhibiting Wee1) and a negative feedback loop (MPF stimulates its own destruction by indirectly activating the ubiquitin pathway that degrades its cyclin subunit). To uncover the full dynamical possibilities of the control system, we translate the regulatory network into a set of differential equations and study these equations by graphical techniques and computer simulation. The positive feedback loops in the model account for thresholds and time lags in cyclin-induced and MPF-induced activation of MPF, and the model can be fitted quantitatively to these experimental observations. The negative feedback loop is consistent with observed time lags in MPF-induced cyclin degradation. Furthermore, our model indicates that there are two possible mechanisms for autonomous oscillations. One is driven by the positive feedback loops, resulting in phosphorylation and abrupt dephosphorylation of the Cdc2 subunit at an inhibitory tyrosine residue. These oscillations are typical of oocyte extracts. The other type is driven by the negative feedback loop, involving rapid cyclin turnover and negligible phosphorylation of the tyrosine residue of Cdc2. The early mitotic cycles of intact embryos exhibit such characteristics. In addition, by assuming that unreplicated DNA interferes with M-phase initiation by activating the phosphatases that oppose MPF in the positive feedback loops, we can simulate the effect of addition of sperm nuclei to oocyte extracts, and the lengthening of cycle times at the mid-blastula transition of intact embryos. This model is hosted on BioModels Database and identified by: BIOMD0000000107. To cite BioModels Database, please use: BioModels: ten-year anniversary . To the extent possible under law, all copyright and related or neighbouring rights to this encoded model have been dedicated to the public domain worldwide. Please refer to CC0 Public Domain Dedication for more information.