Julie Theriot

Professional Education

• Ph.D., Univ. California, San Francisco Cell Biology (1993)
• B.S., Mass. Institute of Technology Biology (1988)
• B.S., Mass. Institute of Technology Physics (1988)

Postdoctoral Advisees

• Eliane Trepagnier, Guy Ziv

Graduate & Fellowship Program Affiliations

• Biochemistry
• Biophysics
• Microbiology and Immunology

Web Site Links

• http://cmgm.stanford.edu/theriot

Research Interests

We study the interactions between infectious bacteria and the human host cell actin cytoskeleton. Listeria monocytogenes and Shigella flexneri are unrelated food-borne bacterial pathogens that share a common mechanism of invasion and actin-dependent intercellular spread in epithelial cells. Our studies fall into three broad areas: the biochemical basis of actin-based motility by these bacteria, the biophysical mechanism of force generation, and the evolutionary origin of pathogenesis.

Medical studies of bacterial diseases have traditionally focused on the behavior of the bacteria themselves and on the response of the host immune system to infection. However, recent advances in our understanding of the cell biology of host-pathogen relationships indicate that disease-causing bacteria have developed extraordinarily complex and subtle ways of communicating with the host. It is clear that infection is not a process performed solely by a bacterium, but rather an elaborately choreographed interaction between the bacterium and the host cell. Using a combination of videomicroscopy, biochemistry, and molecular genetics, we study the interactions between infectious bacteria and the human host cell cytoskeleton. By examining the mechanisms these bacteria use to communicate with the host cell cytoskeleton, we hope to identify new ways to interfere with the infection process, and arrive at a deeper understanding of the normal regulation of cytoskeletal shape changes and cell movement.

Listeria monocytogenes is a ubiquitous Gram-positive bacterium that can cause serious food-borne infections in pregnant women, newborns, and immunocompromised adults. Shigella flexneri is an unrelated Gram-negative bacterium, a causative agent of bacillary dysentery. Both grow directly in the cytoplasm of infected host cells, and move rapidly throughout the infected cell using a remarkable form of actin-based motility. Within a few hours after infection, host cell actin filaments initially form a dense cloud around the intracytoplasmic bacteria, and then rearrange to form a polarized "comet tail," which is associated with all moving bacteria. The comet tail is made up of short actin filaments crosslinked into a meshwork in which the majority of filaments have their barbed (rapidly growing) ends oriented toward the bacterium. We have demonstrated that new actin filament polymerization occurs only at the front of the tail, adjacent to the surface of the bacterium, and that polymerization occurs at the same rate as bacterial propulsion. Bacteria spread from cell to cell by moving into long membrane-bound protrusions that are phagocytosed by neighboring cells. We have found that a single bacterial surface protein is necessary and sufficient for motility in each organism; ActA in L. monocytogenes and IcsA in Shigella flexneri. Surprisingly, these two proteins share no primary sequence similarity, though their functions are essentially identical.

Publications

• Intracellular fluid flow in rapidly moving cells. Keren K,  Yam PT, Kinkhabwala A, Mogilner A, Theriot JA.  Nat Cell Biol.  2009; 11 (10): 1219-24
• Close packing of Listeria monocytogenes ActA, a natively unfolded protein, enhances F-actin assembly without dimerization. Footer MJ,  Lyo JK, Theriot JA.  J Biol Chem.  2008; 283 (35): 23852-62
• Mechanism of shape determination in motile cells. Keren K,  Pincus Z, Allen GM, Barnhart EL, Marriott G, Mogilner A, Theriot JA.  Nature.  2008; 453 (7194): 475-80
• Actin-myosin network reorganization breaks symmetry at the cell rear to spontaneously initiate polarized cell motility. Yam PT,  Wilson CA, Ji L, Hebert B, Barnhart EL, Dye NA, Wiseman PW, Danuser G, Theriot JA.  J Cell Biol.  2007; 178 (7): 1207-21
• Emergence of large-scale cell morphology and movement from local actin filament growth dynamics. Lacayo CI,  Pincus Z, VanDuijn MM, Wilson CA, Fletcher DA, Gertler FB, Mogilner A, Theriot JA.  PLoS Biol.  2007; 5 (9): e233
• Reduced amino acid alphabets exhibit an improved sensitivity and selectivity in fold assignment. Peterson EL,  Kondev J, Theriot JA, Phillips R.  Bioinformatics.  2009; 25 (11): 1356-62
• Direct measurement of force generation by actin filament polymerization using an optical trap. Footer MJ,  Kerssemakers JW, Theriot JA, Dogterom M.  Proc Natl Acad Sci U S A.  2007; 104 (7): 2181-6
• Comparison of quantitative methods for cell-shape analysis. Pincus Z,  Theriot JA.  J Microsc.  2007; 227 (Pt 2): 140-56
• Decoupling the coupling: surface attachment in actin-based motility. Tsuchida MA,  Theriot JA.  ACS Chem Biol.  2007; 2 (4): 221-4
• Differential force microscope for long time-scale biophysical measurements. Choy JL,  Parekh SH, Chaudhuri O, Liu AP, Bustamante C, Footer MJ, Theriot JA, Fletcher DA.  Rev Sci Instrum.  2007; 78 (4): 043711
• A kinematic description of the trajectories of Listeria monocytogenes propelled by actin comet tails. Shenoy VB,  Tambe DT, Prasad A, Theriot JA.  Proc Natl Acad Sci U S A.  2007; 104 (20): 8229-34
• Listeria monocytogenes traffics from maternal organs to the placenta and back. Bakardjiev AI,  Theriot JA, Portnoy DA.  PLoS Pathog.  2006; 2 (6): e66
• A correlation-based approach to calculate rotation and translation of moving cells. Wilson CA,  Theriot JA.  IEEE Trans Image Process.  2006; 15 (7): 1939-51
• Fine-scale time-lapse analysis of the biphasic, dynamic behaviour of the two Vibrio cholerae chromosomes. Fiebig A,  Keren K, Theriot JA.  Mol Microbiol.  2006; 60 (5): 1164-78
• Mechanism of polarization of Listeria monocytogenes surface protein ActA. Rafelski SM,  Theriot JA.  Mol Microbiol.  2006; 59 (4): 1262-79
• Listeria monocytogenes invades the epithelial junctions at sites of cell extrusion. Pentecost M,  Otto G, Theriot JA, Amieva MR.  PLoS Pathog.  2006; 2 (1): e3
• Bacterial shape and ActA distribution affect initiation of Listeria monocytogenes actin-based motility. Rafelski SM,  Theriot JA.  Biophys J.  2005; 89 (3): 2146-58
• Large-scale quantitative analysis of sources of variation in the actin polymerization-based movement of Listeria monocytogenes. Soo FS,  Theriot JA.  Biophys J.  2005; 89 (1): 703-23
• Two independent spiral structures control cell shape in Caulobacter. Dye NA,  Pincus Z, Theriot JA, Shapiro L, Gitai Z.  Proc Natl Acad Sci U S A.  2005; 102 (51): 18608-13
• Loading history determines the velocity of actin-network growth. Parekh SH,  Chaudhuri O, Theriot JA, Fletcher DA.  Nat Cell Biol.  2005; 7 (12): 1219-23
• Adhesion controls bacterial actin polymerization-based movement. Soo FS,  Theriot JA.  Proc Natl Acad Sci U S A.  2005; 102 (45): 16233-8
• Complex spatial distribution and dynamics of an abundant Escherichia coli outer membrane protein, LamB. Gibbs KA,  Isaac DD, Xu J, Hendrix RW, Silhavy TJ, Theriot JA.  Mol Microbiol.  2004; 53 (6): 1771-83
• Crawling toward a unified model of cell mobility: spatial and temporal regulation of actin dynamics. Rafelski SM,  Theriot JA.  Annu Rev Biochem.  2004; 73 209-39
• Bacteria make tracks to the pole. Fiebig A,  Theriot JA.  Proc Natl Acad Sci U S A.  2004; 101 (23): 8510-1
• Comparative analysis of gene expression among low G+C gram-positive genomes. Karlin S,  Theriot J, Mrázek J.  Proc Natl Acad Sci U S A.  2004; 101 (16): 6182-7
• Listeria monocytogenes actin-based motility varies depending on subcellular location: a kinematic probe for cytoarchitecture. Lacayo CI,  Theriot JA.  Mol Biol Cell.  2004; 15 (5): 2164-75
• Biophysical parameters influence actin-based movement, trajectory, and initiation in a cell-free system. Cameron LA,  Robbins JR, Footer MJ, Theriot JA.  Mol Biol Cell.  2004; 15 (5): 2312-23
• Repeated cycles of rapid actin assembly and disassembly on epithelial cell phagosomes. Yam PT,  Theriot JA.  Mol Biol Cell.  2004; 15 (12): 5647-58
• Discovery of antivirals against smallpox. Harrison SC,  Alberts B, Ehrenfeld E, Enquist L, Fineberg H, McKnight SL, Moss B, O'Donnell M, Ploegh H, Schmid SL, Walter KP, Theriot J.  Proc Natl Acad Sci U S A.  2004; 101 (31): 11178-92
• Differentiation and developmental pathways of uropathogenic Escherichia coli in urinary tract pathogenesis. Justice SS,  Hung C, Theriot JA, Fletcher DA, Anderson GG, Footer MJ, Hultgren SJ.  Proc Natl Acad Sci U S A.  2004; 101 (5): 1333-8
• High affinity, paralog-specific recognition of the Mena EVH1 domain by a miniature protein. Golemi-Kotra D,  Mahaffy R, Footer MJ, Holtzman JH, Pollard TD, Theriot JA, Schepartz A.  J Am Chem Soc.  2004; 126 (1): 4-5
• An introduction to cell motility for the physical scientist. Fletcher DA,  Theriot JA.  Phys Biol.  2004; 1 (1-2): T1-10
• Influences of thermal acclimation and acute temperature change on the motility of epithelial wound-healing cells (keratocytes) of tropical, temperate and Antarctic fish. Ream RA,  Theriot JA, Somero GN.  J Exp Biol.  2003; 206 (Pt 24): 4539-51
• Listeria monocytogenes rotates around its long axis during actin-based motility. Robbins JR,  Theriot JA.  Curr Biol.  2003; 13 (19): R754-6
• Ena/VASP proteins contribute to Listeria monocytogenes pathogenesis by controlling temporal and spatial persistence of bacterial actin-based motility. Auerbuch V,  Loureiro JJ, Gertler FB, Theriot JA, Portnoy DA.  Mol Microbiol.  2003; 49 (5): 1361-75
• A gene-expression program reflecting the innate immune response of cultured intestinal epithelial cells to infection by Listeria monocytogenes. Baldwin DN,  Vanchinathan V, Brown PO, Theriot JA.  Genome Biol.  2003; 4 (1): R2
• Compression forces generated by actin comet tails on lipid vesicles. Giardini PA,  Fletcher DA, Theriot JA.  Proc Natl Acad Sci U S A.  2003; 100 (11): 6493-8
• A hitchhiker's guide to cell biology: exploitation of host-cell functions by intracellular pathogens. Rafelski SM,  Theriot JA.  Genome Biol.  2002; 3 (3): REPORTS4006
• The making of a gradient: IcsA (VirG) polarity in Shigella flexneri. Robbins JR,  Monack D, McCallum SJ, Vegas A, Pham E, Goldberg MB, Theriot JA.  Mol Microbiol.  2001; 41 (4): 861-72
• Effects of intermediate filaments on actin-based motility of Listeria monocytogenes. Giardini PA,  Theriot JA.  Biophys J.  2001; 81 (6): 3193-203
• Actin-based motility is sufficient for bacterial membrane protrusion formation and host cell uptake. Monack DM,  Theriot JA.  Cell Microbiol.  2001; 3 (9): 633-47
• Cytoskeleton. Goldstein LS,  Theriot JA.  Curr Opin Cell Biol.  2001; 13 (1): 17-8
• Systematic mutational analysis of the amino-terminal domain of the Listeria monocytogenes ActA protein reveals novel functions in actin-based motility. Lauer P,  Theriot JA, Skoble J, Welch MD, Portnoy DA.  Mol Microbiol.  2001; 42 (5): 1163-77
• Dendritic organization of actin comet tails. Cameron LA,  Svitkina TM, Vignjevic D, Theriot JA, Borisy GG.  Curr Biol.  2001; 11 (2): 130-5
• The polymerization motor. Theriot JA,  Traffic.  2000; 1 (1): 19-28
• Secrets of actin-based motility revealed by a bacterial pathogen. Cameron LA,  Giardini PA, Soo FS, Theriot JA.  Nat Rev Mol Cell Biol.  2000; 1 (2): 110-9
• Functional analysis of a rickettsial OmpA homology domain of Shigella flexneri icsA. Charles M,  Magdalena J, Theriot JA, Goldberg MB.  J Bacteriol.  1999; 181 (3): 869-78
• Cooperative symmetry-breaking by actin polymerization in a model for cell motility. van Oudenaarden A,  Theriot JA.  Nat Cell Biol.  1999; 1 (8): 493-9
• Motility of ActA protein-coated microspheres driven by actin polymerization. Cameron LA,  Footer MJ, van Oudenaarden A, Theriot JA.  Proc Natl Acad Sci U S A.  1999; 96 (9): 4908-13
• Listeria monocytogenes exploits normal host cell processes to spread from cell to cell. Robbins JR,  Barth AI, Marquis H, de Hostos EL, Nelson WJ, Theriot JA.  J Cell Biol.  1999; 146 (6): 1333-50
• Imaging techniques in microbiology. Fung DC,  Theriot JA.  Curr Opin Microbiol.  1998; 1 (3): 346-51
• Listeria monocytogenes-based assays for actin assembly factors. Theriot JA,  Fung DC.  Methods Enzymol.  1998; 298 114-22
• Caged fluorescent probes. Mitchison TJ,  Sawin KE, Theriot JA, Gee K, Mallavarapu A.  Methods Enzymol.  1998; 291 63-78
• New wrinkles in cytokinesis. Theriot JA,  Satterwhite LL.  Nature.  1997; 385 (6615): 388-9
• Accelerating on a treadmill: ADF/cofilin promotes rapid actin filament turnover in the dynamic cytoskeleton. Theriot JA,  J Cell Biol.  1997; 136 (6): 1165-8
• The tandem repeat domain in the Listeria monocytogenes ActA protein controls the rate of actin-based motility, the percentage of moving bacteria, and the localization of vasodilator-stimulated phosphoprotein and profilin. Smith GA,  Theriot JA, Portnoy DA.  J Cell Biol.  1996; 135 (3): 647-60
• Tails from the hall of infection: actin-based motility of pathogens. Sanders MC,  Theriot JA.  Trends Microbiol.  1996; 4 (6): 211-3
• Worm sperm and advances in cell locomotion. Theriot JA,  Cell.  1996; 84 (1): 1-4
• The importance of being random. Theriot JA,  Curr Biol.  1996; 6 (8): 912-3
• The cell biology of infection by intracellular bacterial pathogens. Theriot JA,  Annu Rev Cell Dev Biol.  1995; 11 213-39
• Asymmetric distribution of the Listeria monocytogenes ActA protein is required and sufficient to direct actin-based motility. Smith GA,  Portnoy DA, Theriot JA.  Mol Microbiol.  1995; 17 (5): 945-51
• Shigella flexneri surface protein IcsA is sufficient to direct actin-based motility. Goldberg MB,  Theriot JA.  Proc Natl Acad Sci U S A.  1995; 92 (14): 6572-6
• Involvement of profilin in the actin-based motility of L. monocytogenes in cells and in cell-free extracts. Theriot JA,  Rosenblatt J, Portnoy DA, Goldschmidt-Clermont PJ, Mitchison TJ.  Cell.  1994; 76 (3): 505-17
• Actin-dependent motile forces and cell motility. Cramer LP,  Mitchison TJ, Theriot JA.  Curr Opin Cell Biol.  1994; 6 (1): 82-6
• Actin filament dynamics in cell motility. Theriot JA,  Adv Exp Med Biol.  1994; 358 133-45
• Dynamic actin structures stabilized by profilin. Finkel T,  Theriot JA, Dise KR, Tomaselli GF, Goldschmidt-Clermont PJ.  Proc Natl Acad Sci U S A.  1994; 91 (4): 1510-4
• Regulation of surface presentation of IcsA, a Shigella protein essential to intracellular movement and spread, is growth phase dependent. Goldberg MB,  Theriot JA, Sansonetti PJ.  Infect Immun.  1994; 62 (12): 5664-8
• Regulation of the actin cytoskeleton in living cells. Theriot JA,  Semin Cell Biol.  1994; 5 (3): 193-9
• Expression and phosphorylation of the Listeria monocytogenes ActA protein in mammalian cells. Brundage RA,  Smith GA, Camilli A, Theriot JA, Portnoy DA.  Proc Natl Acad Sci U S A.  1993; 90 (24): 11890-4
• Principles of locomotion for simple-shaped cells. Lee J,  Ishihara A, Theriot JA, Jacobson K.  Nature.  1993; 362 (6416): 167-71
• The three faces of profilin. Theriot JA,  Mitchison TJ.  Cell.  1993; 75 (5): 835-8
• The rate of actin-based motility of intracellular Listeria monocytogenes equals the rate of actin polymerization. Theriot JA,  Mitchison TJ, Tilney LG, Portnoy DA.  Nature.  1992; 357 (6375): 257-60
• The nucleation-release model of actin filament dynamics in cell motility. Theriot JA,  Mitchison TJ.  Trends Cell Biol.  1992; 2 (8): 219-22
• Bacterial pathogens caught in the actin. Theriot JA,  Curr Biol.  1992; 2 (12): 649-51
• The rate of actin-based motility of intracellular Listeria monocytogenes is equal to the rate of actin polymerization. Theriot, J. A.,  Mitchison, T. J., Tilney, L. G. and Portnoy, D. A.  Nature.  1992; (357): 257-260
• Comparison of actin and cell surface dynamics in motile fibroblasts. Theriot JA,  Mitchison TJ.  J Cell Biol.  1992; 119 (2): 367-77
• Actin microfilament dynamics in locomoting cells. Theriot JA,  Mitchison TJ.  Nature.  1991; 352 (6331): 126-31
• Regulation of transcript encoding the 43K subsynaptic protein during development and after denervation. Baldwin TJ,  Theriot JA, Yoshihara CM, Burden SJ.  Development.  1988; 104 (4): 557-64
• 300-kD subsynaptic protein copurifies with acetylcholine receptor-rich membranes and is concentrated at neuromuscular synapses. Woodruff ML,  Theriot J, Burden SJ.  J Cell Biol.  1987; 104 (4): 939-46