New York Academy of Science Remembers Marshall Nirenberg
On July 31, the New York Academy of Sciences honored the work of Marshall Nirenberg – father of the genetic code. Nirenberg is often credited with deciphering the genetic code, ie, determining what the string of A’s, T’s, G’s, and C’s in DNA mean in terms of protein sequence. The event was held on the 50th anniversary of Nirenberg’s presentation at the International Union of Biochemistry and Molecular Biology meeting in New York in which he described a method to identify all 64 codons.
The atmosphere was more like a family reunion than a scientific conference, with Nirenberg’s former students and post docs paying tribute to their mentor. Two presentations in particular truly demonstrated how far science has come in transforming biology into an engineering science.
The first was by Lei Wang of the Salk Institute. Wang uses the redundancy of the genetic code to his advantage. By engineering tRNA synthetases that recognize a stop codon within mRNA, Wang can introduce non-natural amino acids into proteins. The new amino acid can incorporate new functionality – such as fluorescence or metal chelation – into the protein. In his talk at NYAS, Wang focused on bioreactive amino acids, which can introduce the ability to form covalent bonds – either within or between proteins. Wang described two such non-natural amino acids – Ffact, which forms bonds with cysteine residues, and BrClek, which forms bonds with histidine residues. One application of these amino acids is to increase the thermal stability of proteins, thus increasing the shelf life of protein therapeutics.
The second talk that illustrated a re-engineering of the genetic code was by Philipp Holliger of the MRC Laboratory of Molecular Biology, Cambridge, UK. Holliger creates synthetic nucleic acid polymers using “XNA” building blocks, which resemble DNA and RNA. Similar to Wang, Holliger capitalized on the cell’s own system. He has engineered polymerases that synthesize XNA polymers by reading a DNA template as well as reverse transcriptases that do the opposite – make DNA from an XNA polymer. One of the goals of this project is to create aptamer-based therapeutics that are resistant to the body’s nucleases.