Publications by authors named "Anthony Meger"

Article Synopsis
  • The study explores how the function of proteins shapes their fitness landscapes, distinguishing between smooth landscapes (where small changes lead to gradual function variations) and rugged landscapes (where changes result in unpredictable function shifts).
  • Through examining 1,158 sequences from the LacI/GalR transcriptional repressor family, the research found a rugged landscape with rapid changes in specificity between closely related sequences.
  • The ruggedness of this landscape is linked to the need for the repressor to evolve a specific function while avoiding conflicting regulatory interactions, providing new insights into the evolution of genetic regulation.
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Bacteriophages can adapt to new hosts by altering sequence motifs through recombination or convergent evolution. Where such motifs exist and what fitness advantage they confer remains largely unknown. We report a new method, Metagenomic Sequence Informed Functional Scoring (Meta-SIFT), to discover sequence motifs in metagenomic datasets that can be used to engineer phage activity.

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The interaction between a bacteriophage and its host is mediated by the phage's receptor binding protein (RBP). Despite its fundamental role in governing phage activity and host range, molecular rules of RBP function remain a mystery. Here, we systematically dissect the functional role of every residue in the tip domain of T7 phage RBP (1660 variants) by developing a high-throughput, locus-specific, phage engineering method.

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Splitting bioactive proteins into conditionally reconstituting fragments is a powerful strategy for building tools to study and control biological systems. However, split proteins often exhibit a high propensity to reconstitute, even without the conditional trigger, limiting their utility. Current approaches for tuning reconstitution propensity are laborious, context-specific or often ineffective.

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Allostery is a fundamental regulatory mechanism of protein function. Despite notable advances, understanding the molecular determinants of allostery remains an elusive goal. Our current knowledge of allostery is principally shaped by a structure-centric view, which makes it difficult to understand the decentralized character of allostery.

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