Identifying the phase diagram structure for optimal information integration in morphogen systems

Gene regulatory networks (GRNs) perform a wide range of biological functions. It is, however, often challenging to reveal their functioning mechanism with the conventional approach focusing on the network topological structure from a bottom-up perspective. Here, we apply the top-down approach based on the optimality theory to study the information integration in morphogen systems, and show that the optimal integration strategy raises requirement on the phase diagram, rather than the topological structure, of a GRN. For the morphogen system in early fly embryos, our parameter-free model can quantitatively predict the patterning position shifts upon the dosage change of the morphogen Bicoid

Monte Carlo simulation of melting transition on DNA nanocompartment

DNA nanocompartment is a typical DNA-based machine whose function is dependent of molecular collective effect. Fundamental properties of the device have been addressed via electrochemical analysis, fluorescent microscopy, and atomic force microscopy. Interesting and novel phenomena emerged during the switching of the device. We have found that DNAs in this system exhibit a much steep melting transition compared to ones in bulk solution or conventional DNA array. To achieve an understanding to this discrepancy, we introduced DNA-DNA interaction potential to the conventional Ising-like Zimm-Bragg theory and Peyrard-Bishop model of DNA melting. To avoid unrealistic numerical calculation caused by modification of the Peyrard-Bishop nonlinear Hamiltonian with the DNA-DNA interaction, we established coarse-gained Monte Carlo recursion relations by elucidation of five components of energy change during melting transition. The result suggests that DNA-DNA interaction potential accounts for the observed steep transition.Comment: 12 pages, 5 figure

Mixed halide perovskites for spectrally stable and high-efficiency blue light-emitting diodes.

Bright and efficient blue emission is key to further development of metal halide perovskite light-emitting diodes. Although modifying bromide/chloride composition is straightforward to achieve blue emission, practical implementation of this strategy has been challenging due to poor colour stability and severe photoluminescence quenching. Both detrimental effects become increasingly prominent in perovskites with the high chloride content needed to produce blue emission. Here, we solve these critical challenges in mixed halide perovskites and demonstrate spectrally stable blue perovskite light-emitting diodes over a wide range of emission wavelengths from 490 to 451 nanometres. The emission colour is directly tuned by modifying the halide composition. Particularly, our blue and deep-blue light-emitting diodes based on three-dimensional perovskites show high EQE values of 11.0% and 5.5% with emission peaks at 477 and 467 nm, respectively. These achievements are enabled by a vapour-assisted crystallization technique, which largely mitigates local compositional heterogeneity and ion migration

Low Cell-Matrix Adhesion Reveals Two Subtypes of Human Pluripotent Stem Cells.

We show that a human pluripotent stem cell (hPSC) population cultured on a low-adhesion substrate developed two hPSC subtypes with different colony morphologies: flat and domed. Notably, the dome-like cells showed higher active proliferation capacity and increased several pluripotent genes' expression compared with the flat monolayer cells. We further demonstrated that cell-matrix adhesion mediates the interaction between cell morphology and expression of KLF4 and KLF5 through a serum response factor (SRF)-based regulatory double loop. Our results provide a mechanistic view on the coupling among adhesion, stem cell morphology, and pluripotency, shedding light on the critical role of cell-matrix adhesion in the induction and maintenance of hPSC

Studies of temperature-dependent electronic transduction on DNA hairpin loop sensor

A self-assembly monolayer (SAM) of hairpin DNA can be formed on a gold substrate in order to make special biosensors. Labeling the hairpin loop probes with electroactive compositions rather than a fluorophore illustrates interesting profiles of redox current versus temperature. For a biosensor interacting with perfectly complementary targets, the profile shows a characteristic plateau, which disappears when the targets have a single base variation. The plateau is split into multiple steps by tuning the hybridization temperature. We propose that the phenomena are due to hairpin loop compartmentalization. The novel characteristics lead to a thermal gradient detection method that permits perfect discrimination of a target sequence from single nucleotide mismatches

Singly Flagellated Pseudomonas Aeruginosa Chemotaxes Efficiently by Unbiased Motor Regulation

Pseudomonas aeruginosa is an opportunistic human pathogen that has long been known to chemotax. More recently, it has been established that chemotaxis is an important factor in the ability of P. aeruginosa to make biofilms. Genes that allow P. aeruginosa to chemotax are homologous with genes in the paradigmatic model organism for chemotaxis, Escherichia coli. However, P. aeruginosa is singly flagellated and E. coli has multiple flagella. Therefore, the regulation of counterclockwise/ clockwise flagellar motor bias that allows E. coli to efficiently chemotax by runs and tumbles would lead to inefficient chemotaxis by P. aeruginosa, as half of a randomly oriented population would respond to a chemoattractant gradient in the wron sense. How P. aeruginosa regulates flagellar rotation to achieve chemotaxis is not known. Here, we analyze the swimming trajectories of single cells in microfluidic channels and the rotations of cells tethered by their flagella to the surface of a variableenvironment flow cell. We show that P. aeruginosa chemotaxes by symmetrically increasing the durations of both counterclockwise and clockwise flagellar rotations when swimming up the chemoattractant gradient and symmetrically decreasing rotation durations when swimming down the chemoattractant gradient. Unlike the case for E. coli, the counterclockwise/clockwise bias stays constant for P. aeruginosa. We describe P. aeruginosa’s chemotaxis using an analytical model for symmetric motor regulation. We use this model to do simulations that show that, given P. aeruginosa’s physiological constraints on motility, its distinct, symmetric regulation of motor switching optimizes chemotaxis.This work, including the efforts of Vernita Gordon, was funded by UT Austin (startup funds). This work, including the efforts of Qi Ouyang, Chunxiong Luo, and Zhaojun Li, was funded by NSF of China (11174012 and 11434001). This work, including the efforts of Qiuxian Cai, was funded by China Scholarship Council (CSC) (fellowship). This work, including the efforts of Vernita Gordon, was funded by the Exxon Mobil Corporation (gift).Center for Nonlinear Dynamic

The dynamic-process characterization and prediction of synthetic gene circuits by dynamic delay model

Summary: Differential equation models are widely used to describe genetic regulations, predict multicomponent regulatory circuits, and provide quantitative insights. However, it is still challenging to quantitatively link the dynamic behaviors with measured parameters in synthetic circuits. Here, we propose a dynamic delay model (DDM) which includes two simple parts: the dynamic determining part and the doses-related steady-state-determining part. The dynamic determining part is usually supposed as the delay time but without a clear formula. For the first time, we give the detail formula of the dynamic determining function and provide a method for measuring all parameters of synthetic elements (include 8 activators and 5 repressors) by microfluidic system. Three synthetic circuits were built to show that the DDM can notably improve the prediction accuracy and can be used in various synthetic biology applications

The regulatory mechanism of the yeast osmoresponse under different glucose concentrations

Summary: Cells constantly respond to environmental changes by modulating gene expression programs. These responses may demand substantial costs and, thus, affect cell growth. Understanding the regulation of these processes represents a key question in biology and biotechnology. Here, we studied the responses to osmotic stress in glucose-limited environments. By analyzing seventeen osmotic stress-induced genes and stress-activated protein kinase Hog1, we found that cells exhibited stronger osmotic gene expression response and larger integral of Hog1 nuclear localization during adaptation to osmotic stress under glucose-limited conditions than under glucose-rich conditions. We proposed and verified that in glucose-limited environment, glycolysis intermediates (representing “reserve flux”) were limited, which required cells to express more glycerol-production enzymes for stress adaptation. Consequently, the regulatory mechanism of osmoresponse was derived in the presence and absence of such reserve flux. Further experiments suggested that this reserve flux-dependent stress-defense strategy may be a general principle under nutrient-limited environments