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Embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) derived from somatic cells (SCs) provide promising resources for regenerative medicine and medical research, leading to a daily identification of new cell lines.…
Genetically encoded regulatory circuits control biological function. A major focus of systems biology is to understand these circuits by establishing the relationship between specific structures and functions. Of special interest are…
We study a mechanism for reliable switching in biomolecular signal-transduction cascades. Steady bistable states are created by system-size cooperative effects in populations of proteins, in spite of the fact that the phosphorylation-state…
DNA looping plays a fundamental role in a wide variety of biological processes, providing the backbone for long range interactions on DNA. Here we develop the first model for DNA looping by an arbitrarily large number of proteins and solve…
Signal duration (e.g. the time scales over which an active signaling intermediate persists) is a key regulator of biological decisions in myriad contexts such as cell growth, proliferation, and developmental lineage commitments.…
Living organisms rely on molecular networks, such as gene circuits and signaling pathways, for information processing and robust decision-making in crowded, noisy environments. Recent advances show that interacting biomolecules…
Mounting evidence shows that oscillatory activity is widespread in cell signaling. Here we review some of this recent evidence, focusing on both the molecular mechanisms that potentially underlie such dynamical behavior, and the potential…
Epigenetic Tracking is a mathematical model of biological cells, originally conceived to study embryonic development. Computer simulations proved the capacity of the model to generate complex 3-dimensional cellular structures, and the…
Neuronal networks alternate between high- and low-activity regimes, known as up and down states. They also display rhythmic patterns essential for perception, memory consolidation, and sensory processing. Despite their importance, the…
Dynamics maintaining diversity of cell types in a multi-cellular system are studied in relationship with the plasticity of cellular states. By adopting a simple theoretical framework for intra-cellular chemical reaction dynamics with…
We present a general computational theory of stem cell networks and their developmental dynamics. Stem cell networks are special cases of developmental control networks. Our theory generates a natural classification of all possible stem…
The dynamics of active matter driven by interacting molecular motors has a non-potential structure at the local scale. However, we show that there exists a quasi-potential effectively describing the collective self-organization of the…
The formation of polarized signaling domains on cell membranes is a fundamental example of biological pattern formation. While such patterns resemble structures from equilibrium phase separation, they are intrinsically non-equilibrium,…
We consider a heteroclinic network in the framework of winnerless competition of species. It consists of two levels of heteroclinic cycles. On the lower level, the heteroclinic cycle connects three saddles, each representing the survival of…
Presented with sensory challenges, living cells employ extensive noisy, fluctuating signalling and communication among themselves to compute a physiologically proper response which often results in symmetry breaking. We propose, based on…
The complexity of the cells can be described and understood by a number of networks such as protein-protein interaction, cytoskeletal, organelle, signalling, gene transcription and metabolic networks. All these networks are highly dynamic…
The different cell types in a living organism acquire their identity through the process of cell differentiation in which the multipotent progenitor cells differentiate into distinct cell types. Experimental evidence and analysis of…
Based on symmetry consideration of migration and shape deformations, we formulate phenomenologically the dynamics of cell crawling in two dimensions. Forces are introduced to change the cell shape. The shape deformations induce migration of…
Biological functions in living cells are controlled by protein interaction and genetic networks. These molecular networks should be dynamically stable against various fluctuations which are inevitable in the living world. In this paper, we…
To advance understanding of cellular metabolism and reduce batch-to-batch variability in cell culture processes, this study introduces a multi-scale hybrid modeling framework designed to simulate and predict the dynamic behavior of CHO cell…