RESEARCH
I study gene expression in yeast. I am most interested in the fine-tuning rules governing mRNA translation.
HOW DO SYNONYMS SHAPE GENETIC MESSAGES?
The genetic code uses synonyms to convey its message and, like language, synonyms are not always interchangeable. But when does a synonym-swap yield improvements? When does it yield disasters? Fluency in the grammatical rules of the genetic language equips us to better design mRNAs for vaccines, therapeutics, food production, and more.
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GENE EXPRESSION
In each of your cells your genome is constantly being accessed, so that DNA can be transcribed into mRNA, which is translated into protein. This process is called gene expression. Proteins fold as they're being synthesized.
THE CODE
Your body is comprised of chemicals. The chemical building blocks of DNA and RNA are called nucleotides. We symbolize each of the four chemicals with the letters A, T or U, C, and G.
DECRYPTING
mRNA is decoded into amino aids three nucleotides at a time. These nucleotide triplets are called codons.
REDUNDANCY IN THE CODE
Amino acids are encoded by one to six codons. Codons that encode the same amino acid are called synonymous codons.
SYNONYMOUS, NOT THE SAME
Codons decode at different speeds. Usually synonymous codons can be interchanged without incident, but sometimes swapping codons causes problems.
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Slowing translation in a position where it needs to be fast, or vice versa, can affect protein folding, abundance, and function.
CODON CHANGE AND FITNESS
In one assay, I demonstrated a fitness impact upon changing synonymous codons. I exchanged contiguous slow codons for fast codons in a yeast biosynthesis gene.
Yeast with fast-translating codons grew more slowly than yeast with slow-translating codons.
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This indicates that the translation slow down along this mRNA is critical for this protein's function. The effect of changing a few synonymous codons was severe enough to impact the whole organism!
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