Design principles of protein networks

Uri and Gefen

Bionumbers

Uri's book cover
New textbook on systems biology
Solutions Manual for exercises available for instructors
Video lectures of "Introduction to Systems Biology" course

PDF

More Materials for Nurturing Scientists

Our lab picture 11/2007

Understanding the protein circuits that perform computations within the cell is a central problem in biology. From the point of view of physics, cells offer the challenge of understanding the collective behavior of interacting molecular machines designed to operate with remarkable precision under strong biological constraints. Our lab studies biological networks and circuits using a combined experimental and theoretical approach, aiming to uncover general underlying principles that govern their functioning.

Topics of interest:

To understand biological networks, our lab has defined "network motifs": basic interaction patterns that recur throughout biological networks, much more often than in random networks. The same small set of network motifs appears to serve as the building blocks of transcription networks from bacteria to mammals. Specific network motifs are also found in signal transduction networks, neuronal networks and other biological and non-biological networks.

We experimentally studied the function of each network motif in the transcription network of E. coli. Each network motifs can serve as an elementary circuit with a defined function: filters, pulse generators, response accelerators, temporal-pattern-generators and more. Evolution seems to have converged on the same motifs again and again, perhaps because they are the simplest and most robust circuits that perform these information-processing functions.

Our lab also studies topics in evolution, experimentally and theoretically. We measured the cost and benefit of gene expression in E. coli, and demonstrated in evolutionary experiments that protein levels evolve to maximize fitness within a few hundred generations. Other studies are on the origin of modularity in biological systems, and on the plasticity of the input functions of genes.

These experiments are performed using novel systems for measuring the behavior of gene circuits within living cells. We developed a library of 2000 E. coli strains in which green fluorescent protein reports for the activity of the vast majority of the organisms' promoters. We also developed ‘dynamic proteomics’, a system for dynamic monitoring of a thousand different proteins in individual living human cells (see movies).

Recently, we started a theatre lab, in which we use concepts from improvisation theatre, and tools from physics, neurobiology and computer science, to study basic principles of human interactions. Our first project studied the phenomenon of togetherness- moments of high performance and synchrony reported by improvising musicians and actors. We used a theater practice called the mirror game to find that two people can create complex novel motion together without a designated leader or follower (see publication).