A5052704218- RNA and protein synthesis mechanisms
- Bacterial Genetics and Biotechnology
- Gene Regulatory Network Analysis
- Microbial Metabolic Engineering and Bioproduction
- Theoretical and Computational Physics
- Protein Structure and Dynamics
- Genomics and Phylogenetic Studies
- Evolution and Genetic Dynamics
- Physics of Superconductivity and Magnetism
- Bacteriophages and microbial interactions
- Algorithms and Data Compression
- Microbial Community Ecology and Physiology
- Complex Systems and Time Series Analysis
- Evolutionary Game Theory and Cooperation
- RNA Research and Splicing
- Stochastic processes and statistical mechanics
- Micro and Nano Robotics
- Bioinformatics and Genomic Networks
- Nonlinear Dynamics and Pattern Formation
- Nanopore and Nanochannel Transport Studies
- Cell Image Analysis Techniques
- Diffusion and Search Dynamics
- Material Dynamics and Properties
- Gut microbiota and health
- Genomics and Chromatin Dynamics
University of California, San Diego
2016-2025
Technical University of Denmark
2024
ETH Zurich
2014-2024
Technical University of Munich
2024
Instituto de Física Teórica
2016
Center for Theoretical Biological Physics
2005-2014
University of Illinois Urbana-Champaign
2012
Loewe Center for Synthetic Microbiology
2011
Harvard University Press
2008
North Carolina State University
2008
The similarity in the three-dimensional structures of homologous proteins imposes strong constraints on their sequence variability. It has long been suggested that resulting correlations among amino acid compositions at different positions can be exploited to infer spatial contacts within tertiary protein structure. Crucial this inference is ability disentangle direct and indirect correlations, as accomplished by recently introduced direct-coupling analysis (DCA). Here we develop a...
In bacteria, the rate of cell proliferation and level gene expression are intimately intertwined. Elucidating these relations is important both for understanding physiological functions endogenous genetic circuits designing robust synthetic systems. We describe a phenomenological study that reveals intrinsic constraints governing allocation resources toward protein synthesis other aspects growth. A theory incorporating can accurately predict how affect one another, quantitatively accounting...
Understanding the molecular determinants of specificity in protein–protein interaction is an outstanding challenge postgenome biology. The availability large protein databases generated from sequences hundreds bacterial genomes enables various statistical approaches to this problem. In context covariance-based methods have been used identify correlation between amino acid positions interacting proteins. However, these important shortcoming, that they cannot distinguish directly and...
Cells receive a wide variety of cellular and environmental signals, which are often processed combinatorially to generate specific genetic responses. Here we explore theoretically the potentials limitations combinatorial signal integration at level cis-regulatory transcription control. Our analysis suggests that many complex transcription-control functions type encountered in higher eukaryotes already implementable within much simpler bacterial system. Using quantitative model invoking only...
The Burgers equation is the simplest nonlinear generalization of diffusion equation. We present a detailed dynamical renormalization-group analysis this subject to random noise. noise itself can be product another stochastic process and hence allowed have correlations in space and/or time. In dimensions higher than critical ${d}_{c}$ weak strong lead different scaling exponents, while for d${d}_{c}$ any amount relevant resulting strong-coupling behavior. absence temporal we find two regimes...
Bacteria must constantly adapt their growth to changes in nutrient availability; yet despite large-scale protein expression associated with sensing, adaptation, and processing different environmental nutrients, simple laws connect the ribosome abundance rate. Here, we investigate origin of these by analyzing features ribosomal regulation that coordinate proteome-wide cell a variety conditions model organism Escherichia coli. We identify supply-driven feedforward activation synthesis as key...
A synthetic circuit implementing density-controlled bacterial motility autonomously produces a tunable stripe pattern.
An increasing number of small RNAs (sRNAs) have been shown to regulate critical pathways in prokaryotes and eukaryotes. In bacteria, regulation by trans-encoded sRNAs is predominantly found the coordination intricate stress responses. The mechanisms which modulate expression its targets are diverse. common most possibility that interference with translation mRNA may also alter abundance functional sRNAs. Aiming understand unique role played gene regulation, we studied examples from two...
Article12 February 2015Open Access Quantitative proteomic analysis reveals a simple strategy of global resource allocation in bacteria Sheng Hui Department Physics, University California at San Diego, La Jolla, CA, USA Search for more papers by this author Josh M Silverman Integrative Structural and Computational Biology, The Skaggs Institute Chemical Scripps Research Institute, Chemistry, Stephen S Chen David W Erickson Markus Basan Jilong Wang Terence Hwa Corresponding Author Section...
Significance In rapidly growing bacteria, one-third of the proteins are ribosomal and another one-sixth ternary complexes (TCs) that bring amino acids to ribosomes, making TCs most abundant protein species. This study reveals this very high TC content is forced upon cell due slow diffusion large in crowded cytoplasm. A model presented describe how a bacterial solves problem proteomic resource allocation, balancing two requirements for many ribosomes rapid translation. The shows proportional...
We introduce a theoretical framework that exploits the ever-increasing genomic sequence information for protein structure prediction. Structure-based models are modified to incorporate constraints by large number of non-local contacts estimated from direct coupling analysis (DCA) co-evolving sequences. A simple hybrid method, called DCA-fold, integrating DCA with an accurate knowledge local (e.g., secondary structure) is sufficient fold proteins in range 1–3 Å resolution.
Abstract Understanding how the homeostasis of cellular size and composition is accomplished by different organisms an outstanding challenge in biology. For exponentially growing Escherichia coli cells, it long known that cells exhibits a strong positive relation with their growth rates nutrient conditions. Here, we characterized cell sizes set orthogonal limitations. We report mass exhibit or negative dependences rate depending on limitation applied. In particular, synthesizing large amounts...
To predict the emergence of antibiotic resistance, quantitative relations must be established between fitness drug-resistant organisms and molecular mechanisms conferring resistance. These are often unknown may depend on state bacterial growth. bridge this gap, we have investigated Escherichia coli strains expressing resistance to translation-inhibiting antibiotics. We show that expression drug inhibition linked in a positive feedback loop arising from an innate, global effect drug-inhibited...
New experimental results on bacterial growth inspire a novel top-down approach to study cell metabolism, combining mass balance and proteomic constraints extend complement Flux Balance Analysis. We introduce here Constrained Allocation Analysis, CAFBA, in which the biosynthetic costs associated are accounted for an effective way through single additional genome-wide constraint. Its roots lie experimentally observed pattern of proteome allocation metabolic functions, allowing bridge...