U Alon

..Here I review network motifs and their functions, with an emphasis on experimental studies. Network motifs in other biological networks are also mentioned, including signalling and neuronal networks...

..We experimentally find this order reversal under the predicted conditions. This study supports a view in which the evolutionary path to adaptation in a new environment can be captured by theory and experiment...

..This is a step toward understanding the human ability to create novelty by improvising together...

..The input function that we studied thus appears to be plastic, in the sense that many of the mutations do not ruin the regulation completely but rather result in new ways to integrate the inputs...

..To address this, we studied the negative auto-regulation motif in the arabinose utilization system of Escherichia coli, in which negative auto-regulation is part of a complex regulatory network...

..Here, I describe how to prepare, present, and answer questions in a scientific talk. We will see how a talk prepared with a single premise and delivered with good eye contact is clear and enjoyable...

..It highlights the surprising discovery of "good-engineering" principles in biochemical circuitry that evolved by random tinkering...

..Motivated group members experience a full sense of choice: of doing what one wants. Such behavior shows high performance, is enjoyable, and enhances innovation. This essay describes principles of building a motivated research group...

..This lack of explicit discussion leaves a vacuum that can lead to approaches such as choosing problems that can give results that merit publication in valued journals, resulting in a job and tenure...

..We asked how PEP formation rate, a key step in the carbon fixation pathway, might work at a precise rate, regulated by light, despite fluctuations in substrate and enzyme levels constituting and regulating this process...

..Using mathematical modeling, we describe the information processing functions of the different motif generalizations in transcription, neuronal, and electronic networks...

..Response acceleration may be performed by the incoherent feed-forward loop modules that are found in diverse systems from bacteria to humans...

..The observed temporal program of transcription was much more detailed than was previously thought and was associated with multiple steps of flagella assembly...

..The motif structure also allows an easily interpretable view of the entire known transcriptional network of the organism. This approach may help define the basic computational elements of other biological networks...

..The present cost-benefit theory can be used to understand the shape of other gene regulatory functions in terms of environment and noise constraints...

..This information-processing function may be performed by the feedforward loop regulation modules that are found in diverse systems from bacteria to humans...

..The total number of transcription factors encoded in a genome increases with the number of genes in the genome. Here, we examined the number of transcription factors from each super-family in diverse organisms...

..Instead, we suggest a robust mechanism where both substrates bind the bifunctional enzyme to form a ternary complex...

..Thus, our approach provides an efficient tool for studying dynamic relationship between components of systems of interest at a single-cell level...

..This agrees with an analytical solution of a mathematical model for negative autoregulation. This may help in understanding the function of negative autoregulation, which appears in over 40% of known transcription factors in E.coli...

..The raw movies may be useful as a benchmark for developing image analysis tools for individual-cell dynamic-proteomics. The database is available at http://www.dynamicproteomics.net/...

..Thus, biochemical parameters, noise, and slowly varying cellular states together determine the effective single-cell GRF. These results can form a basis for quantitative modeling of natural gene circuits and for design of synthetic ones...

..This study highlights a fundamental difference between the architecture of sensory and developmental transcription networks...

..The error-minimization framework raises several experimentally testable hypotheses. It may also apply to other biological regulation systems, such as those involving protein-protein interactions...

..This first broad survey of two-dimensional input functions can be extended to map the logic of gene regulation in other systems...

..Thus, environments that change in a systematic, modular fashion seem to promote facilitated variation and allow evolution to generalize to novel conditions...

..This approach can be generally used to study the evolutionary selection of other network motifs...

..Additional features, such as pulse generation and cooperativity, are discussed. This study defines the function of one of the most significant recurring circuit elements in transcription networks...

..In particular, the model suggests a mechanism for the dramatic speedup in evolution observed under such temporally varying goals...

..The SUM-FFL in this system works as theoretically predicted despite being embedded in at least two additional feedback loops. The present function might be carried out by the SUM-FFL in systems found across organisms...

..This may be due to differences in the pair-wise energy functions used and the dynamic nature of these proteins. AVAILABILITY: A web-based tool to calculate network motifs is available at http://bioinfo.weizmann.ac.il/protmot/...

..The present study thus experimentally demonstrates how upstream circuitry can affect gene input functions and how an I1-FFL functions within its natural context in the cell...

..The present approach can be used to define blueprints of other gene networks and to quantitatively reprogram their dynamics...

..This finding opens the possibility of assigning kinetic parameters to transcriptional networks on a genomic scale...

..Additional superfamilies include power grids, protein-structure networks and geometric networks, World Wide Web links and social networks, and word-adjacency networks from different languages...

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..Thus, protein expression from the lac operon seems to be a solution of a cost-benefit optimization problem, and can be rapidly tuned by evolution to function optimally in new environments...

..Tasks can be inferred from measured phenotypes based on the behavior of organisms nearest the archetypes...

..AVAILABILITY: A software tool for estimating subgraph concentrations and detecting network motifs (mfinder 1.1) and further information is available at http://www.weizmann.ac.il/mcb/UriAlon/..

..We identify proteins whose dynamics differ widely between cells, in a way that corresponds to the outcomes-cell death or survival. This opens the way to understanding molecular responses to drugs in individual cells...

..Motifs may thus define universal classes of networks. This approach may uncover the basic building blocks of most networks...

..This possibility means that the wild-type region is selected to perform an elaborate computation in setting the transcription rate. The present approach can be generally used to map the input functions of other genes...

..The present study may shed light on the evolutionary forces that promote structural simplicity in biological networks and offers ways to improve the evolutionary design of engineered systems...

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..Our findings suggest that metabolic regulation networks are designed to generate precision promoter timing and activity programs that can be understood using the engineering principles of production pipelines...

..The persistent memory for protein levels that we found might underlie individuality in cell behaviour and could set a timescale needed for signals to affect fully every member of a cell population...

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..Our technique should provide a quantitative internal calibration to systems biology studies of both synthetic and endogenous cellular networks...

..This study suggests, therefore, that extinctions in heterogeneous environments promote the evolution of modular biological network structure, allowing local populations to effectively recombine their modules to recolonize niches...

..This approach to dynamic proteomics can aid in discovery and accurate quantification of the extensive regulation of protein concentration and localization in individual living cells...

..coli, including putative internal promoters within previously known operons, such as the lac operon. This library can serve as a tool for accurate, high-resolution analysis of transcription networks in living E. coli cells...

..This study suggests that varying environments might significantly contribute to the speed of natural evolution. In addition, it suggests a way to accelerate optimization algorithms and improve evolutionary approaches in engineering...

..Thus gene functional order may be inferred by analyzing the operon structure across different genomes...

..More generally, our study proposes a mechanistic description of the cellular response to growth factors by defining architectural motifs that underlie the function of signaling networks...

..This demonstration that quantitative characterization of regulatory elements can predict the behavior of genetic circuits supports a fundamental requirement of synthetic biology...

..This study provides a view of the extensive variability of the behavior of a protein circuit in living human cells, both from cell to cell and in the same cell over time...

..This suggests an optimality principle for the structure of central carbon metabolism. The present approach may be used to study other metabolic networks and to design new minimal pathways...

..It seems to be a useful way to find the in vivo design of circuits and may be applied to other systems by monitoring their power spectrum in individual cells...

..It explains how specific molecular details can work together to provide robustness. Moreover, it suggests an approach that can help identify a wide family of nonequilibrium mechanisms that potentially have robust input-output relations...

..Whereas many of the known regulatory codes reside in nontranslated regions of the genome, the present findings suggest that protein-coding regions can readily carry abundant additional information...

..The present approach may be used to simplify a variety of directed and nondirected, natural and designed networks...

..Our approach might eliminate the need to increase the number of experiments exponentially with the number of drugs and suggests that it might be possible to rationally control protein dynamics with specific drug combinations...

..Virtually all four-protein motifs consisted of combinations of smaller motifs. This study presents a basic framework for detecting the building blocks of networks with multiple types of interactions...