The Macromolecules and Interfaces Institute and the Fralin Life Science Institute at Virginia Tech are pleased to announce that David Tirrell, the Ross McCollum-William H. Corcoran Professor of Chemistry and Chemical Engineering and Director of the Beckman Institute at the California Institute of Technology, will be the Fralin-MII Visiting Scholar from Nov. 12-15.

Tirrell is a world-renowned polymer and materials scientist whose research involves the application of organic, biological, and materials chemistry to make new macromolecular systems of controlled size and shape and novel functional performance characteristics. A major focus of his research is the design and synthesis of new proteins based on the use of non-canonical amino acids in recombinant DNA techniques to prepare artificial proteins with specific design and performance characteristics. Tirrell’s contributions have earned him membership in the Institute of Medicine and the American Academy of Arts and Sciences. He has also won numerous medals and awards from various scientific societies.

Tirrell will deliver three lectures that demonstrate the progress and potential of using molecular genetics to bridge the gap between the synthetic polymer/materials sciences and the biology/protein sciences. These lectures are open to the entire Virginia Tech community and also to neighboring academic and industrial students and scientists.  Lectures will be held in the ICTAS-I (headquarters) building seminar room (310). Tirrell will also be available to participate in informal faculty and student discussions. Meetings can be scheduled through the Macromolecules and Interfaces Institute office by contacting Tammy Jo Hiner.  A list of hotels for overnight guests is also available. 

"The theme of our successful Visiting Scholar activity is to enhance interdisciplinary interactions among the polymer and materials communities and the life science communities on the Virginia Tech campus and we are extremely pleased to sponsor our third visiting scholar in this series," said Dennis Dean, director of life sciences at Virginia Tech.

"Professor David Tirrell is the pioneer in bridging synthetic macromolecular science with the biology and biomedical engineering communities and we are delighted that he will share his science with our students and faculty," said S. Richard Turner, director of the Macromolecules and Interfaces Institute.  

The overall theme of Tirrell's three lectures is summarized in the following title and description:

"Reinterpreting the Genetic Code: From Polymers to Proteomics" 

The genetic code, elucidated in the 1960s through the work of Nirenberg, Ochoa, Khorana and their coworkers, provides a set of molecular instructions for translating nucleic acids into proteins. Codons are assigned to amino acids through high-fidelity charging of transfer RNAs, and through accurate base-pairing between charged tRNAs and messenger RNA. Over the last decade, cells have been outfitted with modified translational machinery that enables the participation of an expanded set of amino acids in protein synthesis. These developments have stimulated a unified view of the chemistry of natural and synthetic macromolecules, and provide a basis for powerful new approaches to materials design, protein evolution, biological imaging, and proteome-wide analysis of cellular processes.

The specific titles, location and times of each lecture are listed below:

  • Lecture 1: Genetically Programmed Synthesis of Novel Macromolecules (Monday, Nov. 12, 310 ICTAS-I, 11:15 a.m.-12:15 p.m.): The first lecture will provide an overview of the use of molecular genetics to prepare novel macromolecules.  The motivation for adopting this approach will be discussed, along with challenges in implementation.  Use of the approach to control macromolecular assembly, to evolve proteins of novel composition, and to engineer proteins for therapeutic applications will be described.  Results of recent clinical trials will be presented.
  • Lecture 2: Proteins that Nature Never Made (Tuesday, Nov. 13, 310 ICTAS-I, 11:15 a.m.-12:15 p.m.) Macromolecular chemistry has traditionally been divided into two fields, with biochemists and biochemical engineers working on proteins and nucleic acids while polymer chemists and materials scientists have concerned themselves with synthetic polymers. These two classes of macromolecules are profoundly different from one another; proteins and nucleic acids are uniform, well folded, and evolvable, whereas polymers are heterogeneous and for the most part adopt random-coil conformations. These differences in molecular structure and behavior have led to striking differences in the ways in which natural and synthetic polymers are used-- largely for information storage and transfer in biology, and largely as materials in the technological world. This lecture will describe an ongoing attempt to bridge the gap between polymers and proteins by using artificial genes to direct the synthesis of artificial proteins in bacterial cells, and to combine the physical and informational properties of macromolecules.
  • Lecture 3: Non-Canonical Amino Acids in the Interrogation of Cellular Protein Synthesis (Thursday, Nov. 15, 310 ICTAS-I, 11:15 a.m.-12:15 p.m.) Proteins can be rendered susceptible to bio-orthogonal chemistries through metabolic labeling with appropriately designed, non-canonical amino acids (ncAAs). In the simplest approach to metabolic labeling, an amino acid analog replaces, in whole or in part, one of the natural amino acids specified by the protein gene(s) of interest. This approach allows the ncAA to be introduced at a controlled rate into positions normally occupied by the natural amino acid residue. Because this approach permits labeling of proteins throughout the cell, it has enabled us to develop strategies to track cellular protein synthesis by tagging proteins with reactive ncAAs.

In procedures similar to those used in isotopic labeling, translationally active ncAAs are incorporated into proteins during a “pulse” in which newly synthesized proteins are tagged. The set of tagged proteins can be distinguished from those made prior to the pulse through bio-orthogonal ligation of the ncAA side chain to probes that permit detection, isolation, and visualization of the labeled proteins. The selectivity of the method can be enhanced through the use of mutant aminoacyl-tRNA synthetases (aaRSs) that permit incorporation of ncAAs that are not used by the endogenous machinery. Controlled expression of mutant synthetases has been combined with ncAA-tagging to permit cell-selective and state-selective metabolic labeling of proteins. Expression of a mutant synthetase in a subset of cells in a complex cellular mixture -- or in a live animal -- restricts labeling to that subset; proteins synthesized in cells that do not express the synthetase are neither labeled nor detected.



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