The Logic Backbone of a Transcription Network

The structure and dynamics of a typical biological system are complex due to strong and inhomogeneous interactions between its constituents. The investigation of such systems with classical mathematical tools, such as differential equations for their dynamics, is not always suitable. The graph theoretical models may serve as a rough but powerful tool in such cases. In this thesis, I first consider the network modeling for the representation of the biological systems. Both the...

Many biological systems approach physical limits to their performance, motivating the idea that their behavior and underlying mechanisms could be determined by such optimality. Nevertheless, optimization as a predictive principle has only been applied in very simplified setups. Here, in contrast, we explore a mechanistically-detailed class of models for the gap gene network of the Drosophila embryo, and determine its 50+ parameters by optimizing the information that gene expr...

Understanding design principles of molecular interaction networks is an important goal of molecular systems biology. Some insights have been gained into features of their network topology through the discovery of graph theoretic patterns that constrain network dynamics. This paper contributes to the identification of patterns in the mechanisms that govern network dynamics. The control of nodes in gene regulatory, signaling, and metabolic networks is governed by a variety of b...

In this paper we investigate equilibria of continuous differential equation models of network dynamics. The motivation comes from gene regulatory networks where each directed edge represents either down- or up-regulation, and is modeled by a sigmoidal nonlinear function. We show that the existence and stability of equilibria of a sigmoidal system is determined by a combinatorial analysis of the limiting switching system with piece-wise constant non-linearities. In addition, w...

Gene regulatory networks (GRNs) play a central role in cellular decision-making. Understanding their structure and how it impacts their dynamics constitutes thus a fundamental biological question. GRNs are frequently modeled as Boolean networks, which are intuitive, simple to describe, and can yield qualitative results even when data is sparse. We assembled the largest repository of expert-curated Boolean GRN models. A meta-analysis of this diverse set of models reveals sever...

Here we propose a new approach to modeling gene expression based on the theory of random dynamical systems (RDS) that provides a general coupling prescription between the nodes of any given regulatory network given the dynamics of each node is modeled by a RDS. The main virtues of this approach are the following: (i) it provides a natural way to obtain arbitrarily large networks by coupling together simple basic pieces, thus revealing the modularity of regulatory networks; (i...

A Boolean network is a finite state discrete time dynamical system. At each step, each variable takes a value from a binary set. The value update rule for each variable is a local function which depends only on a selected subset of variables. Boolean networks have been used in modeling gene regulatory networks. We focus in this paper on a special class of Boolean networks, namely the conjunctive Boolean networks (CBNs), whose value update rule is comprised of only logic AND o...

This Thesis presents research at the boundary between Statistical Physics and Biology. First, we have devised a class of Boolean constraint satisfaction problems (CSP) whose solutions describe the feasible operational states of a chemical reaction network. After developing statistical mechanics techniques to generate solutions and studying the properties of the solution space for both ensembles and individual instances of random reaction networks, we have applied this framewo...

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 randomness of individual molecular events. Here we explore how cells can maximize their control power in the presence of these physical limits; formally, we solve the theoretical problem of maximizing the information transferred from input...

The engineered control of cellular function through the design of synthetic genetic networks is becoming plausible. Here we show how a naturally occurring network can be used as a parts list for artificial network design, and how model formulation leads to computational and analytical approaches relevant to nonlinear dynamics and statistical physics.