David A. Tirrell
Provost; Carl and Shirley Larson Provostial Chair; Ross McCollum-William H. Corcoran Professor of Chemistry and Chemical Engineering
Research InterestsBiocatalysis; Biomaterials; Polymer Science; Protein Engineering; Macromolecular Chemistry
Assistant: Irina Meininger
Research in the Tirrell group combines organic, biological, and materials chemistry to make new macromolecular systems of controlled architecture and novel function.
Artificial proteins represent a new class of macromolecular materials that bridge the gap that has traditionally separated natural polymers from their synthetic counterparts. While synthetic polymers are interesting and enormously important, their utility derives in large part from their physical properties; chemists have yet to capture in synthetic polymers the more subtle catalytic and informational properties of proteins and nucleic acids. The reason for this distinction lies in the levels of architectural control to be found in each class of polymers; proteins and nucleic acids are characterized by defined lengths, sequences, and stereochemistries, while synthetic polymers are highly heterogeneous molecular mixtures. This raises interesting questions about the kinds of novel science and engineering that could be done if new macromolecular architectures could be created with precise control of the most important structural variables.
Microbial expression of artificial genes provides a means of doing just that. The process begins with molecular design--the specification of a chain structure that the investigator believes will exhibit interesting (and perhaps useful) behavior. The target structure is then encoded into an artificial gene, and the gene is expressed in an appropriate microbial host. Current targets include reversible hydrogels and artificial extracellular matrices for use in tissue regeneration and repair.
An important theme of all of our projects is the development of methods for efficient incorporation of new monomers (beyond the twenty "normal" amino acids) into proteins made in vivo. The chemistry of non-canonical amino acids enables important new approaches to biomaterials design, protein modification, proteomic analysis and protein evolution.