Description:

The Department of Pharmacology and the Center for Synthetic Biology are pleased to present a seminar by Faculty Candidate, Ross Thyer, Ph.D., Postdoctoral Research Fellow, Center for Systems and Synthetic Biology, University of Texas at Austin.

Below is a brief description of the seminar as described by Dr. Thyer:

The sequence of a protein defines its structure and ultimately its function. While traditional protein engineering efforts have greatly enhanced our ability to customize nature and resulted in the modern bioeconomy, some functionality is difficult or impossible to achieve with standard protein sequences. Nature's solution to this problem is to expand the pool of building blocks available for protein synthesis through the use of non-canonical amino acids such as selenocysteine, a rare, naturally occurring amino acid which has a mosaic distribution across all domains of life. Unlike canonical amino acids, selenocysteine does not exist freely, and is directly synthesized on its tRNA which is pre-charged with serine. In bacteria, selenocysteine is co-translationally incorporated in response to specific opal stop codons, designated by the presence of a selenocysteine insertion sequence (SECIS) element which recruits the selenocysteine specific elongation factor and charged tRNASec needed to reassign the UGA codon. The SECIS element is a stem-loop RNA structure immediately following the UGA codon and forms part of the coding sequence in bacterial selenoproteins. With a low pKa and strong nucleophilicity, the site specific incorporation of selenocysteine has great potential for protein engineering, but the sequence constraints imposed by the adjoining SECIS element severely limit its use. Using an amber suppressor tRNASec variant and a recoded E. coli host to overcome these problems, we have produced new recombinant seleno-scFvs with improved formation of covalent diselenide bonds and increased resistance to reducing conditions compared to their disulfide counterparts.