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How do organisms control codon decoding?

Codon decoding is a central process in gene expression to synthesize proteins from genetic codes on mRNAs. Modulating the efficiency and accuracy of codon decoding is crucial for diverse cellular processes. Kimura Lab aims to define how microorganisms, including human pathogens and commensals, adjust their codon decoding processes for adaptation and resilience to diverse environments.

Profiles and functions of tRNA modifications

tRNA modification is chemical transformation where RNA nucleosides are converted into diverse structures. tRNA modification controls the abundance and decoding properties of tRNAs to optimize codon decoding processes. Individual organisms have distinct profiles and functions of tRNA modifications; however, tRNA modification has not been profiled in most organisms. Using a high-throughput pipeline, which led to the discovery of novel RNA modification and RNA editing process in Cholera pathogen, we conduct comprehensive profiling of tRNA modifications in pathogens and commensals to uncover organism-specific tRNA modifications and decoding systems. Such organism-specific decoding system can be novel targets of therapeutics.

Translation mechanisms underlying bacterial pathogenesis

Pathogens undergo drastic environmental changes during infection, such as nutrient limitation, exposure to stresses and antibiotic. Adaptation to such diverse conditions is crucial for robust pathogenesis. Many genome-wide genetic screen suggest that pathogens' translation modulation mechanisms are essential for efficient colonization to the host and adaptation to various stresses. However, their mechanisms are largely unclear. Using cutting-edge approaches, including Next-gen sequencing, RNA mass spectrometry, and  infection models, we investigate how pathogens modulate their translation mechanisms to adapt to environmental changes for their pathogenesis. By investigating the pathogens' translation control mechanisms in the context of infection, we aim to deepen our understanding of bacterial pathogenesis to lay the foundation for new therapeutics.

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