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The capacity of proteins to interact specifically with one another underlies our conceptual understanding of how living systems function. Systems-level study of specificity in protein-protein interactions is complicated by the fact that the…
Recent studies reported complex post-transcriptional interplay among targets of a common pool of microRNAs, a class of small non-coding downregulators of gene expression. Behaving as microRNA-sponges, distinct RNA species may compete for…
Molecular networks guide the biochemistry of a living cell on multiple levels: its metabolic and signalling pathways are shaped by the network of interacting proteins, whose production, in turn, is controlled by the genetic regulatory…
Signal transduction networks can form highly interconnected systems within cells due to network crosstalk, the sharing of input signals between multiple downstream responses. To better understand the evolutionary design principles…
Predictive understanding of the myriads of signal transduction pathways in a cell is an outstanding challenge of systems biology. Such pathways are primarily mediated by specific but transient protein-protein interactions, which are…
We quantify the influence of the topology of a transcriptional regulatory network on its ability to process environmental signals. By posing the problem in terms of information theory, we may do this without specifying the function…
How do living cells achieve sufficient abundances of functional protein complexes while minimizing promiscuous non-functional interactions? Here we study this problem using a first-principle model of the cell whose phenotypic traits are…
Living cells sense their environment through the binding of extra-cellular molecular ligands to cell surface receptors. Puzzlingly, vast numbers of signaling pathways exhibit a high degree of cross talk between different signals whereby…
Background:Typically, proteins perform key biological functions by interacting with each other. As a consequence, predicting which protein pairs interact is a fundamental problem. Experimental methods are slow, expensive, and may be error…
Signaling pathways are responsible for the regulation of cell processes, such as monitoring the external environment, transmitting information across membranes, and making cell fate decisions. Given the increasing amount of biological data…
Identity, response to external stimuli, and spatial architecture of a living system are central topics of molecular biology. Presently, they are largely seen as a result of the interplay between a gene repertoire and the regulatory…
Cellular function is widely believed to be organized in a modular fashion. On all scales and at all levels of complexity, relatively independent sub-units perform relatively independent sub-tasks of biological function. This functional…
Signal transduction within biological cells is governed by networks of interacting proteins. Communication between these proteins is mediated by signaling molecules which bind to receptors and induce stochastic transitions between different…
In order to survive, reproduce and (in multicellular organisms) differentiate, cells must control the concentrations of the myriad different proteins that are encoded in the genome. The precision of this control is limited by the inevitable…
Cells need to reliably sense external ligand concentrations to achieve various biological functions such as chemotaxis or signaling. The molecular recognition of ligands by surface receptors is degenerate in many systems leading to…
Eukaryotic cells transmit information by signaling through complex networks of interacting proteins. Here we develop a theoretical and computational framework that relates the biophysics of protein-protein interactions (PPIs) within a…
We present a new experimental-computational technology of inferring network models that predict the response of cells to perturbations and that may be useful in the design of combinatorial therapy against cancer. The experiments are…
Spatial heterogeneity is a hallmark of living systems, even at the molecular scale in individual cells. A key example is the partitioning of membrane-bound proteins via lipid domain formation or cytoskeleton-induced corralling. Yet the…
Regulatory networks consist of interacting molecules with a high degree of mutual chemical specificity. How can these molecules evolve when their function depends on maintenance of interactions with cognate partners and simultaneous…
The evolution, regulation and sustenance of biological complexity is determined by protein-protein interaction network that is filled with dynamic events. Recent experimental evidences point out that clustering of proteins has a vital role…