Research in the Tirrell group combines organic, biological, and materials chemistry to make new biological materials of controlled molecular and supramolecular architectures. Two kinds of systems are under active investigation: artificial proteins made by expression of artificial genes in microbial cells and incorporation of noncanonical amino acids into proteins. In each case, investigators are concerned not only with architectural control but also with the functional properties of the macromolecular system of interest and applications.

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, informational, and transduction properties of proteins and nucleic acids. The reason for this distinction may lie 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 regarding the kinds of materials science that could be done if new macromolecular architectures could be created with precise control of the most important structural variables.

Microbial expressions 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 novel liquid crystal phases, macromolecular surface arrays, reversible hydrogels, and artificial extracellular matrices for use in tissue regeneration and repair. An important theme of all of these projects is the development of methods for efficient incorporation of new monomers (beyond the twenty "normal" amino acids) into artificial proteins in vivo.

California Institute of Technology - Tirrell Lab
MailCode: 210-41 1200 E California Blvd, Pasadena CA 91125

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