Isao Masuda, PhD

My research interest lies in elucidating the mechanism of codon-specific translation and its significance to antibiotic resistance in pathogenic bacteria. In particular, my colleagues and I have focused on the importance of the m1G37 modification on a specific subset of the transfer RNAs (tRNAs). This post-transcriptional modification is generated by a bacterium-specific methyltransferase TrmD. We have shown that this modification is required for an efficient and accurate translation on the ribosome, conferring a strong membrane structure that leads to an antibiotic resistance. In the absence of this modification, increased ribosome stalling and ribosomal frameshift disrupt a normal translation on the ribosome, and cells not only become more susceptible to drugs, but die. By using both genetic and biochemical approaches, we are uncovering the epigenetic regulatory mechanism through a differential, codon-specific translation by m1G37-tRNAs, which fine-tunes the biological processes for the pathogens to survive various stress conditions. Furthermore, the m1G37-tRNAs and the enzyme TrmD are thus essential for bacterial survival, therefore these factors are promising antibacterial targets. We are performing a high-throughput drug screening that targets TrmD, in order to tackle the antibiotic resistance crisis by discovering a novel class of drugs.

PhD, Health Science, School of Medicine, The University of Tokyo, Japan - 2011
MSc, Agriculture, Kyoto University - 2008