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We present an analytically solvable model for self-assembly of a molecular complex on a filament. The process is driven by a seed molecule that undergoes facilitated diffusion, which is a search strategy that combines diffusion in…
An approximation to the ~4 Mbp basic genome shared by 32 strains of E. coli representing six evolutionary groups has been derived and analyzed computationally. A multiple-alignment of the 32 complete genome sequences was filtered to remove…
Reconstructing transcriptional regulatory networks is an important task in functional genomics. Data obtained from experiments that perturb genes by knockouts or RNA interference contain useful information for addressing this reconstruction…
Natural protein sequences contain a record of their history. A common constraint in a given protein family is the ability to fold to specific structures, and it has been shown possible to infer the main native ensemble by analyzing…
RNA interference (RNAi) is a fundamental cellular process that inhibits gene expression through cleavage and destruction of target mRNA. It is responsible for a number of important intracellular functions, from being the first line of…
Proliferation is a defining feature of life. Through growth, division, and death, living systems consume energy and inject mass, breaking conservation laws and driving collective phenomena from biofilm formation to embryonic development.…
Genome-scale metabolic models have become a fundamental tool for examining metabolic principles. However, metabolism is not solely characterized by the underlying biochemical reactions and catalyzing enzymes, but also affected by regulatory…
Explanation of exponential growth in self-reproduction is an important step toward elucidation of the origins of life because optimization of the growth potential across rounds of selection is necessary for Darwinian evolution. To produce…
In living cells, biochemical reactions are catalyzed by specific enzymes and connect to one another by sharing substrates and products, forming complex networks. In our previous studies, we established a framework determining the responses…
Turnover of regulatory sequence and function is an important part of molecular evolution. But what are the modes of sequence evolution leading to rapid formation and loss of regulatory sites? Here, we show that a large fraction of…
Homeostasis of protein concentrations in cells is crucial for their proper functioning, and this requires concentrations (at their steady-state levels) to be stable to fluctuations. Since gene expression is regulated by proteins such as…
In Escherichia coli the response to DNA damage shows strong cell-to-cell-heterogenity. This results in a random delay in cell division and asymmetrical binary fission of single cells, which can compromise the size homeostasis of 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…
Discrete gene regulatory networks (GRNs) play a vital role in the study of robustness and modularity. A common method of evaluating the robustness of GRNs is to measure their ability to regulate a set of perturbed gene activation patterns…
Cell fate decisions in multicellular organisms are precisely coordinated, leading to highly reproducible macroscopic outcomes of developmental processes. The origins of this reproducibility can be found at the molecular level during the…
The lactose operon in Escherichia coli was the first known gene regulatory network, and it is frequently used as a prototype for new modeling paradigms. Historically, many of these modeling frameworks use differential equations. More…
In this thesis, we have studied the large scale structure and system level dynamics of certain biological networks using tools from graph theory, computational biology and dynamical systems. We study the structure and dynamics of large…
Protein expression levels optimize cell fitness: Too low an expression level of essential proteins will slow growth by compromising essential processes; whereas overexpression slows growth by increasing the metabolic load. This trade-off…
Two powerful and complementary experimental approaches are commonly used to study the cell cycle and cell biology: One class of experiments characterizes the statistics (or demographics) of an unsynchronized exponentially-growing…
Most proteins involved in processing DNA accomplish their activities as a monomer or as a component of a multimer containing a relatively small number of other elements. They generally act locally, binding to one or a few small regions of…