个人简介

B.S., Massachusetts Institute of Technology, 1974; M.S., University of Massachusetts, 1976; Ph.D., 1978. D.h.c., Eindhoven Technical University. McCollum-Corcoran Professor and Professor, Caltech, 1998-. Chair, Division of Chemistry and Chemical Engineering, 1999-2009; Director, Beckman Institute, 2012-2018; Provost, 2017-present

研究领域

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.

Biochemistry and Molecular Biophysics; Chemistry; Chemical Engineering

近期论文

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Deforest CA, Tirrell DA. A photoreversible protein-patterning approach for guiding stem cell fate in three-dimensional gels. Nat. Mat. (2015) PMID: 25707020 Yuet KP, Doma MK, Ngo JT, Sweredoski MJ, Graham RLJ, Moradian A, Hess S, Schuman EM, Sternberg PW, Tirrell DA. Cell-specific proteomic analysis in Caenorhabditis elegans. Proc Natl Acad Sci USA. (2015) PMID: 25691744 Feng L, Rutherford ST, Papenfort K, Bagert JD, van Kessel JC, Tirrell DA, Wingreen NS, Bassler BL. A Qrr Noncoding RNA Deploys Four Different Regulatory Mechnanisms to Optimize Quorum-Sensing Dynamics. Cell. 160: 228-240 (2015). PMID: 25579683 Jin L, Feng T, Chai J, Ghazalli N, Gao D, Zerda R, Li Z, Hsu J, Mahdavi A, Tirrell DA, Riggs AD, Ku HT. Colony-Forming Progenitor Cells in the Postnatal Mouse Liver and Pancreas Give Rise to Morphologically Distinct Insulin-Expressing Colonies in 3D Cultures. Rev. Diabet. Stud. 11: 35-50 (2014). PMID: 25148366 Sun F, Zhang W-B, Mahdavi A, Arnold FH, Tirrell DA. Synthesis of bioactive protein hydrogels by genetically encoded SpyTag-SpyCatcher chemistry. Proc Natl Acad Sci USA. 111: 11269-11274 (2014). PMID: 25049400 Van Deventer JA, Yuet KP, Yoo TH, Tirrell DA. Cell Surface Display Yields Evolvable, Clickable Antibody Fragments. Chembiochem. 15: 1777-1781 (2014). PMID: 25045032 Lesman A, Notbohm J, Tirrell DA, Ravichandran G. Contractile forces regulate cell division in three-dimensional environments. J. Cell Biol. 205(2):155-62. (2014). PMID: 24778310 Hatzenpichler R, Scheller S, Tavormina PL, Babin BM, Tirrell DA, Orphan VJ. In situ visualization of newly synthesized proteins in environmental microbes using amino acid tagging and click chemistry. Environ Microbiol. 16: 2568-90 (2014). PMID: 24571640 Bagert JD, Xie Y, Sweredoski M, Qi Y, Hess S, Schuman E, Tirrell DA. Quantitative, Time-Resolved Proteomic Analysis by Combining Bioorthogonal Noncanonical Amino Acid Tagging and Pulsed Stable Isotope Labeling by Amino Acids in Cell Culture. Mol. Cell Prot. 13(5):1352-8. (2014). PMID: 24563536 Tirrell DA. The Wonder of Life in Its Chemical Aspect. Advances in Polymer Science, 261: 199-210. (2013). Mahdavi A, Szychowski J, Ngo JT, Sweredoski MJ, Graham RL, Hess S, Schneewind O, Mazmanian SK, Tirrell DA. Identification of secreted bacterial proteins by noncanonical amino acid tagging. Proc Natl Acad Sci USA. 111(1): 433-8. (2014). PMID: 24347637 Lu Y-Y, Sweredoski M, Huss D, Lansford R, Hess S, Tirrell DA. Prometastatic GPCR CD97 Is a Direct Target of Tumor Suppressor microRNA-126. ACS Chem. Biol. 9: 334-338 (2014). PMID: 24274104 Burts AO, Liao L, Lu Y-Y, Tirrell DA, Johnson JA. Brush-first and click: efficient synthesis of nanoparticles that degrade and release doxorubicin in response to light. Photochem. Photobiol. 90: 380-385 (2014). PMID: 24117423 Yuet KP, Tirrell DA. Chemical Tools for Temporally and Spatially Resolved Mass Spectrometry-Based Proteomics. Ann. Biomed. Eng. 42: 299-311 (2014). PMID: 23943069 Kulkarni C, Kinzer-Ursem TL, Tirrell DA. Selective Functionalization of the Protein N Terminus with N-Myristoyl Transferase for Bioconjugation in Cell Lysate. ChemBioChem. 14: 1958-1962 (2013). PMID: 24030852 Zhang WB, Sun F, Tirrell DA, Arnold FH. Controlling Macromolecular Topology with Genetically Encoded SpyTag-SpyCatcher Chemistry. J. Am. Chem. Soc. 135: 13988-13997 (2013). PMID: 23964715 Tzlil S, Tirrell DA. Strain propagation in artificial extracellular matrix proteins can accelerate cell spreading and polarization. Soft Matter. 9: 5602-5608 (2013). Dooling LJ, Tirrell DA. Peptide and Protein Hydrogels. Polymeric and Self Assembled Hydrogels: From Fundamental Understanding to Applications. XJ Loh and OA Scherman, eds., RSC Publishing, Cambridge, (2013), pp. 93–124. Le DH, Hanamura R, Pham DH, Kato M, Tirrell DA, Okubo T, Sugahara-Narutaki A. Self-Assembly of Elastin-Mimetic Double Hydrophobic Polypeptides. Biomacromolecules. 14: 1028-1034 (2013). PMID:23495825 Ngo JT, Schuman EM, Tirrell DA. Mutant Methionyl-tRNA Synthetase from Bacteria Enables Site-Selective N-terminal Labeling of Proteins Expressed in Mammalian Cells. Proc Natl Acad Sci USA. 110: 4992-4997 (2013). PMID:23479642