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Full-Text Articles in Life Sciences
Heterogeneous Dynamics In Dna Site Discrimination By The Structurally Homologous Dna-Binding Domains Of Ets-Family Transcription Factors, Gaofei He, Ana Tolic, James Bashkin, Gregory Poon
Heterogeneous Dynamics In Dna Site Discrimination By The Structurally Homologous Dna-Binding Domains Of Ets-Family Transcription Factors, Gaofei He, Ana Tolic, James Bashkin, Gregory Poon
Chemistry & Biochemistry Faculty Works
The ETS family of transcription factors exemplifies current uncertainty in how eukaryotic genetic regulators with overlapping DNA sequence preferences achieve target site specificity. PU.1 and Ets-1 represent archetypes for studying site discrimination by ETS proteins because their DNA-binding domains are the most divergent in sequence, yet they share remarkably superimposable DNA-bound structures. To gain insight into the contrasting thermodynamics and kinetics of DNA recognition by these two proteins, we investigated the structure and dynamics of site discrimination by their DNA-binding domains. Electrophoretic mobilities of complexes formed by the two homologs with circularly permuted binding sites showed significant dynamic differences only …
Phenotypic Heterogeneity In Metabolic Traits Among Single Cells Of A Rare Bacterial Species In Its Natural Environment Quantified With A Combination Of Flow Cell Sorting And Nanosims, Matthias Zimmermann, Matthias Zimmermann, Stéphanie Escrig, Thomas Hübschmann, Mathias Kirf, Mathias Kirf, Andreas Brand, Andreas Brand, R. Inglis, R. Inglis, Niculina Musat, Susann Müller, Andres Meibom, Andres Meibom, Martin Ackermann, Martin Ackermann, Frank Schreiber, Frank Schreiber
Phenotypic Heterogeneity In Metabolic Traits Among Single Cells Of A Rare Bacterial Species In Its Natural Environment Quantified With A Combination Of Flow Cell Sorting And Nanosims, Matthias Zimmermann, Matthias Zimmermann, Stéphanie Escrig, Thomas Hübschmann, Mathias Kirf, Mathias Kirf, Andreas Brand, Andreas Brand, R. Inglis, R. Inglis, Niculina Musat, Susann Müller, Andres Meibom, Andres Meibom, Martin Ackermann, Martin Ackermann, Frank Schreiber, Frank Schreiber
Biology Department Faculty Works
Populations of genetically identical microorganisms residing in the same environment can display marked variability in their phenotypic traits; this phenomenon is termed phenotypic heterogeneity. The relevance of such heterogeneity in natural habitats is unknown, because phenotypic characterization of a sufficient number of single cells of the same species in complex microbial communities is technically difficult. We report a procedure that allows to measure phenotypic heterogeneity in bacterial populations from natural environments, and use it to analyze N2 and CO2 fixation of single cells of the green sulfur bacterium Chlorobium phaeobacteroides from the meromictic lake Lago di Cadagno. We incubated lake …
Species Interactions Differ In Their Genetic Robustness, Lon Chubiz, Brian Granger, Daniel Segrè, William Harcombe
Species Interactions Differ In Their Genetic Robustness, Lon Chubiz, Brian Granger, Daniel Segrè, William Harcombe
Biology Department Faculty Works
Conflict and cooperation between bacterial species drive the composition and function of microbial communities. Stability of these emergent properties will be influenced by the degree to which species’ interactions are robust to genetic perturbations. We use genome-scale metabolic modeling to computationally analyze the impact of genetic changes when Escherichia coli and Salmonella enterica compete, or cooperate. We systematically knocked out in silico each reaction in the metabolic network of E. coli to construct all 2583 mutant stoichiometric models. Then, using a recently developed multi-scale computational framework, we simulated the growth of each mutant E. coli in the presence of S. …
Parallel And Divergent Evolutionary Solutions For The Optimization Of An Engineered Central Metabolism In Methylobacterium Extorquens Am1, Sean Carroll, Lon Chubiz, Deepa Agashe, Christopher Marx
Parallel And Divergent Evolutionary Solutions For The Optimization Of An Engineered Central Metabolism In Methylobacterium Extorquens Am1, Sean Carroll, Lon Chubiz, Deepa Agashe, Christopher Marx
Biology Department Faculty Works
Bioengineering holds great promise to provide fast and efficient biocatalysts for methanol-based biotechnology, but necessitates proven methods to optimize physiology in engineered strains. Here, we highlight experimental evolution as an effective means for optimizing an engineered Methylobacterium extorquens AM1. Replacement of the native formaldehyde oxidation pathway with a functional analog substantially decreased growth in an engineered Methylobacterium, but growth rapidly recovered after six hundred generations of evolution on methanol. We used whole-genome sequencing to identify the basis of adaptation in eight replicate evolved strains, and examined genomic changes in light of other growth and physiological data. We observed great variety …
Human Gephyrin Is Encompassed Within Giant Functional Noncoding Yin–Yang Sequences, Sharlee Climer, Alan Templeton, Weixiong Zhang
Human Gephyrin Is Encompassed Within Giant Functional Noncoding Yin–Yang Sequences, Sharlee Climer, Alan Templeton, Weixiong Zhang
Computer Science Faculty Works
Gephyrin is a highly conserved gene that is vital for the organization of proteins at inhibitory receptors, molybdenum cofactor biosynthesis and other diverse functions. Its specific function is intricately regulated and its aberrant activities have been observed for a number of human diseases. Here we report a remarkable yin–yang haplotype pattern encompassing gephyrin. Yin–yang haplotypes arise when a stretch of DNA evolves to present two disparate forms that bear differing states for nucleotide variations along their lengths. The gephyrin yin–yang pair consists of 284 divergent nucleotide states and both variants vary drastically from their mutual ancestral haplotype, suggesting rapid evolution. …
Fighting Microbial Drug Resistance: A Primer On The Role Of Evolutionary Biology In Public Health, Gabriel Perron, R. Inglis, Pleuni Pennings, Sarah Cobey
Fighting Microbial Drug Resistance: A Primer On The Role Of Evolutionary Biology In Public Health, Gabriel Perron, R. Inglis, Pleuni Pennings, Sarah Cobey
Biology Department Faculty Works
Although microbes have been evolving resistance to antimicrobials for millennia, the spread of resistance in pathogen populations calls for the development of new drugs and treatment strategies. We propose that successful, long-term resistance management requires a better understanding of how resistance evolves in the first place. This is an opportunity for evolutionary biologists to engage in public health, a collaboration that has substantial precedent. Resistance evolution has been an important tool for developing and testing evolutionary theory, especially theory related to the genetic basis of new traits and constraints on adaptation. The present era is no exception. The articles in …