Dr. Chris J. Brandl
B.Sc. Western University
Ph.D. University of Toronto
Post-doctoral researcher, Harvard Medical School
Office: Molecular Biology Laboratory C210
Phone: 519.679.2111, ext. 86857
tRNA Biology: Applications in Synthetic Biology and Cellular Function
Our lab has a long-standing interest in the mechanisms regulating gene expression. Our current research projects focus on tRNA biology, mistranslation and evolution of the genetic code. The standard genetic code consists of 61 sense codons that are translated into 20 amino acids and three stop codons designating termination. The accuracy of translation requires high fidelity codon decoding at the ribosome and properly aminoacylated tRNA substrates. tRNA aminoacylation is the first specificity step in translation and is catalyzed by aminoacyl-tRNA synthetases (aaRS), which specifically ligate the amino acid to the 3’ end of a cognate tRNA.
In contrast to the textbook version of translation, life does not require a perfectly accurate proteome. Errors in protein synthesis occur at a rate of one mis-incorporated amino acid in 104 to 105 codons, with cells increasing this to use mistranslation as an adaptive response to cope with different forms of stress. The use of mistranslation as an adaptive response combined with known variation to the code (e.g. mitochondria, C. albicans) plus the decoding of stop codons with pyrrolysine and selenocysteine indicate that the genetic code continues to evolve. Furthermore, mistranslation caused by genetic variation in tRNAs, either to the identity elements responsible for targeting of the correct aaRS or to a tRNA's anticodon, is able to compensate for otherwise deleterious mutations in the cell.
The goals of our research are to
(1) Determine how cells cope and evolve with mistranslation,
(2) Identify tRNA variants that will mistranslate for use in synthetic biology applications, and
(3) Determine the extent to which mistranslation contributes to cellular function, misfunction and disease.
Complete list of publications from PubMed.