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Despite the greater functional importance of protein levels, our knowledge of gene expression evolution is based almost entirely on studies of mRNA levels. In contrast, our understanding of how translational regulation evolves has lagged…
Cellular differentiation is governed by gene regulatory networks, the high-dimensional stochastic biochemical systems that determine the transcriptional landscape and mediate cellular responses to signals and perturbations. Although…
Synthetic biology constructs often rely upon the introduction of "circuit" genes into host cells, in order to express novel proteins and thus endow the host with a desired behavior. The expression of these new genes "consumes" existing…
A simple stochastic model of a self regulating gene that displays bistable switching is analyzed. While on, a gene transcribes mRNA at a constant rate. Transcription factors can bind to the DNA and affect the gene's transcription rate.…
The Unfolded Protein Response is the cell mechanism for maintaining the balance of properly folded proteins in the endoplasmic reticulum , the specialized cellular compartment. Although it is largely studied from a biological point of view,…
Protein synthesis is one of the most fundamental biological processes, which consumes a significant amount of cellular resources. Despite existence of multiple mathematical models of translation, varying in the level of mechanistical…
A crucial step in the regulation of gene expression is binding of transcription factor (TF) proteins to regulatory sites along the DNA. But transcription factors act at nanomolar concentrations, and noise due to random arrival of these…
In this manuscript we propose a mathematical framework to couple transcription and translation in which mRNA production is described by a set of master equations while the dynamics of protein density is governed by a random differential…
Transcriptional and post-transcriptional regulation shape tissue-type-specific proteomes, but their relative contributions remain contested. Estimates of the factors determining protein levels in human tissues do not distinguish between (i)…
Control problem in a biological system is the problem of finding an interventional policy for changing the state of the biological system from an undesirable state, e.g. disease, into a desirable healthy state. Boolean networks are utilized…
Recent advances in DNA sequencing and fluorescence imaging have made it possible to monitor the dynamics of ribosomes actively engaged in messenger RNA (mRNA) translation. Here, we model these experiments within the inhomogeneous totally…
Regulation of mRNA decay is a critical component of global cellular adaptation to changing environments. The corresponding changes in mRNA lifetimes can be coordinated with changes in mRNA transcription rates to fine-tune gene expression.…
Individual mRNAs are translated by multiple ribosomes that initiate translation with a few seconds interval. The ribosome speed is codon dependant, and ribosome queuing has been suggested to explain specific data for translation of some…
Deprivation of essential nutrients can have stark consequences for many processes in a cell. We consider amino acid starvation, which can result in bottlenecks in mRNA translation when ribosomes stall due to lack of resources, i.e. tRNAs…
Despite growth being fundamental to all aspects of cell biology, we do not yet know its organizing principles in eukaryotic cells. Classic models derived from the bacteria E. coli posit that protein-synthesis rates are set by mass-action…
Genetic oscillators are present in the cells of many organisms and control several biological processes. The common feature of such oscillators is the presence of a protein which represses the transcription of its own gene. Recently, it has…
Many {\it ribosomes} simultaneously move on the same messenger RNA (mRNA), each synthesizing separately a copy of the same protein. In contrast to the earlier models, here {\it we develop a ``unified'' theoretical model} that not only…
The ribosome is a macromolecular complex which is responsible for protein synthesis in all living cells according to their transcribed genetic information. Using X-ray crystallography and, more recently, cryo-electron microscopy (cryo-EM),…
One of the greatest challenges in biophysical models of translation is to identify coding sequences features that affect the rate of translation and therefore the overall protein production in the cell. We propose an analytic method to…
Recent progress in large-scale flow and diffusion models raised two fundamental algorithmic challenges: (i) control-based reward adaptation of pre-trained flows, and (ii) integration of multiple models, i.e., flow merging. While current…