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Upinder S Bhalla

Publications and source records attributed to Upinder S Bhalla.

22 records · Page 2Linked to original sources

Mechanisms for temporal tuning and filtering by postsynaptic signaling pathways.

Networks of signaling pathways perform complex temporal decoding functions in diverse biological systems, including the synapse, development, and bacterial chemotaxis. This paper examines temporal filtering and tuning properties of synaptic signaling pathways as a possible substrate for emergent temporal decoding. A mass action kinetic model of 16 synaptic signaling pathways was used to dissect out the contribution of these pathways in linear cascades and when coupled to form a network. The model predicts two primary mechanisms of temporal tuning of pathways: a weighted summation of responses of pathways with different timings and the presence of biochemical feedback loop(s) with emergent dynamics. Regulatory inputs act differently on these two tuning mechanisms. In the first case, regulators act like a gain-control on pathways with different intrinsic tuning. In the case of feedback loops, the temporal properties of the loop itself are changed. These basic tuning mechanisms may underlie specialized temporal tuning functions in more complex signaling systems in biology.

Animals↗

The chemical organization of signaling interactions.

MOTIVATION: Cellular chemical signaling pathways form complex networks that are beginning to be studied at the level of chemical kinetics and databases of reactions. Chemical reaction details are traditionally represented as lists of reactions and rates. This does not map readily to the block diagram representation familiar to biologists, and obscures the functional organization of signaling networks. This study examines motifs in signaling chemistry and reports common features that may help to formalize such a mapping between pathway block diagrams and the chemistry. The same motifs may facilitate data representation and provide functional abstraction of the chemistry. RESULTS: I classified 74 interactions between 25 signaling pathways in terms of shared chemical motifs. All interactions in this dataset consist of a few communicating molecules from one set of pathways, and a replicating set of reactions and molecules from another. Each unique combination of interacting pathways duplicates the chemical reaction scheme of this replicating set, but involves different rate constants. Signaling pathways can therefore be described in an object-oriented manner as sets of core reactions with well-defined interfaces between pathways. This generalization lends itself to designing simulators and databases for signaling networks. AVAILABILITY: Software and example models are freely available from http://www.ncbs.res.in/~bhalla/examples/EGFR_example.html.

Computational Biology↗

Biochemical signaling networks decode temporal patterns of synaptic input.

Synapses exhibit a wide repertoire of responses to different temporal patterns of synaptic input. Many of these responses are expressed as short and long-term changes in synaptic strength. Electrical properties of channels and calcium buildup can account for rapid aspects of pattern decoding, but it is not clear how more complex input patterns, especially those lasting over many minutes, could be discriminated. This paper shows that a network of signaling pathways can discriminate between complex input patterns lasting tens of minutes, and can give rise to distinct combinatorial patterns of biochemical signaling activity in pathways involved in synaptic change. Regulatory signaling input can alter and even reverse the strengths of responses to input patterns. Thus the synaptic signaling network may function as a temporal decoder that transforms patterns from the time domain into the domain of chemical signaling. This may underlie different synaptic responses to different stimulus patterns.

Calcium↗