Dataset Information

Constructing network topologies for multiple signal-encoding functions.

ABSTRACT:

Background

Cells use signaling protein networks to sense their environment and mediate specific responses. Information about environmental stress is usually encoded in the dynamics of the signaling molecules, and qualitatively distinct dynamics of the same signaling molecule can lead to dramatically different cell fates. Exploring the design principles of networks with multiple signal-encoding functions is important for understanding how distinct dynamic patterns are shaped and integrated by real cellular networks, and for building cells with targeted sensing-response functions via synthetic biology.

Results

In this paper, we investigate multi-node enzymatic regulatory networks with three signal-encoding functions, i.e., dynamic responses of oscillation, transient activation, and sustained activation upon step stimulation by three different inducers, respectively. Taking into account competition effects of the substrates for the same enzyme in the enzymatic reactions, we searched for robust subnetworks for each signal-encoding function by three-node-network enumeration and then integrated the three subnetworks together via node-merging. The obtained tri-functional networks consisted of four to six nodes, and the core structures of these networks were hybrids of the motifs for the subfunctions.

Conclusions

The simplest but relatively robust tri-functional networks demonstrated that the three functions were compatible within a simple negative feedback loop. Depending on the network structure, the competition effects of the substrates for the same enzyme within the networks could promote or hamper the target functions, and can create implicit functional motifs. Overall, the networks we obtained could in principle be synthesized to construct dynamic control circuits with multiple target functions.

SUBMITTER: Wu L

PROVIDER: S-EPMC6330498 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Constructing network topologies for multiple signal-encoding functions.

Wu Lili L Wang Hongli H Ouyang Qi Q

BMC systems biology 20190111 1

<h4>Background</h4>Cells use signaling protein networks to sense their environment and mediate specific responses. Information about environmental stress is usually encoded in the dynamics of the signaling molecules, and qualitatively distinct dynamics of the same signaling molecule can lead to dramatically different cell fates. Exploring the design principles of networks with multiple signal-encoding functions is important for understanding how distinct dynamic patterns are shaped and integrate ...[more]

PMID: 30634968

Similar Datasets

Project description:Most models for ethylene signaling involve a linear pathway. However, measurements of seedling growth kinetics when ethylene is applied and removed have resulted in more complex network models that include coherent feedforward, negative feedback, and positive feedback motifs. The dynamical responses of the proposed networks have not been explored in a quantitative manner. Here, we explore (i) whether any of the proposed models are capable of producing growth-response behaviors consistent with experimental observations and (ii) what mechanistic roles various parts of the network topologies play in ethylene signaling. To address this, we used computational methods to explore two general network topologies: The first contains a coherent feedforward loop that inhibits growth and a negative feedback from growth onto itself (CFF/NFB). In the second, ethylene promotes the cleavage of EIN2, with the product of the cleavage inhibiting growth and promoting the production of EIN2 through a positive feedback loop (PFB). Since few network parameters for ethylene signaling are known in detail, we used an evolutionary algorithm to explore sets of parameters that produce behaviors similar to experimental growth response kinetics of both wildtype and mutant seedlings. We generated a library of parameter sets by independently running the evolutionary algorithm many times. Both network topologies produce behavior consistent with experimental observations, and analysis of the parameter sets allows us to identify important network interactions and parameter constraints. We additionally screened these parameter sets for growth recovery in the presence of sub-saturating ethylene doses, which is an experimentally-observed property that emerges in some of the evolved parameter sets. Finally, we probed simplified networks maintaining key features of the CFF/NFB and PFB topologies. From this, we verified observations drawn from the larger networks about mechanisms underlying ethylene signaling. Analysis of each network topology results in predictions about changes that occur in network components that can be experimentally tested to give insights into which, if either, network underlies ethylene responses.

Dataset Information

Constructing network topologies for multiple signal-encoding functions.

Background

Results

Conclusions

Publications

Constructing network topologies for multiple signal-encoding functions.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets