Timothy Mitchison

Summary

Affiliation: Harvard University
Country: USA

Publications

  1. pmc Chromosomal passenger complex hydrodynamics suggests chaperoning of the inactive state by nucleoplasmin/nucleophosmin.
    Mariah L Hanley
    Mol Biol Cell 28:1444-1456. 2017
  2. doi request reprint The engine of microtubule dynamics comes into focus
    T J Mitchison
    Deptartment of Systems Biology, Harvard Medical School, Boston, MA 02115, USA Electronic address
    Cell 157:1008-10. 2014
  3. pmc An intermittent live cell imaging screen for siRNA enhancers and suppressors of a kinesin-5 inhibitor
    Melody Tsui
    Department of Systems Biology, Harvard Medical School, Boston, Massachusetts, United States of America
    PLoS ONE 4:e7339. 2009
  4. pmc The proliferation rate paradox in antimitotic chemotherapy
    Timothy J Mitchison
    Department of Systems Biology, Harvard Medical School, Boston, MA 02115, USA
    Mol Biol Cell 23:1-6. 2012
  5. pmc Rapid de-localization of actin leading edge components with BDM treatment
    Justin C Yarrow
    Dept of Cell Biology, Harvard Medical School, 240 Longwood Ave, Boston, MA 02115, USA
    BMC Cell Biol 4:5. 2003
  6. pmc A high-throughput cell migration assay using scratch wound healing, a comparison of image-based readout methods
    Justin C Yarrow
    Department of Systems Biology, Institute of Chemistry and Cell Biology, Harvard Medical School, Boston, MA 02115, USA
    BMC Biotechnol 4:21. 2004
  7. pmc Mechanism and function of poleward flux in Xenopus extract meiotic spindles
    T J Mitchison
    Department of Systems Biology, Harvard Medical School, Boston, MA, USA
    Philos Trans R Soc Lond B Biol Sci 360:623-9. 2005
  8. pmc Roles of polymerization dynamics, opposed motors, and a tensile element in governing the length of Xenopus extract meiotic spindles
    T J Mitchison
    Marine Biological Laboratory, Woods Hole, MA 02543, USA
    Mol Biol Cell 16:3064-76. 2005
  9. ncbi request reprint Small-molecule screening and profiling by using automated microscopy
    Timothy J Mitchison
    Dept Systems Biology and Institute of Chemistry and Cell Biology, Harvard Medical School, Boston, MA 02115, USA
    Chembiochem 6:33-9. 2005
  10. pmc Bipolarization and poleward flux correlate during Xenopus extract spindle assembly
    T J Mitchison
    Cell Division Group, Marine Biological Laboratory, Woods Hole, MA 02543, USA
    Mol Biol Cell 15:5603-15. 2004

Research Grants

  1. ELECTRON MICROSCOPE
    Timothy Mitchison; Fiscal Year: 2004
  2. ACTIN DYNAMICS AND CELL LOCOMOTION
    Timothy Mitchison; Fiscal Year: 2004
  3. Probing Cell Division with Synthetic Chemistry
    Timothy Mitchison; Fiscal Year: 2008
  4. Cytoskeleton polymerization dynamics in the cell cycle
    Timothy J Mitchison; Fiscal Year: 2010

Collaborators

Detail Information

Publications88

  1. pmc Chromosomal passenger complex hydrodynamics suggests chaperoning of the inactive state by nucleoplasmin/nucleophosmin.
    Mariah L Hanley
    Mol Biol Cell 28:1444-1456. 2017
    ..We propose that nucleophosmin/nucleoplasmin complexes serve as chaperones that negatively regulate the CPC and/or stabilize its inactive form, preventing CPC autophosphorylation and recruitment to chromatin and microtubules in mitosis...
  2. doi request reprint The engine of microtubule dynamics comes into focus
    T J Mitchison
    Deptartment of Systems Biology, Harvard Medical School, Boston, MA 02115, USA Electronic address
    Cell 157:1008-10. 2014
    ..Destabilization of cytoskeleton filaments by nucleotide hydrolysis is an important general principle in cell dynamics, and this work represents a major step forward on a problem with a long history...
  3. pmc An intermittent live cell imaging screen for siRNA enhancers and suppressors of a kinesin-5 inhibitor
    Melody Tsui
    Department of Systems Biology, Harvard Medical School, Boston, Massachusetts, United States of America
    PLoS ONE 4:e7339. 2009
    ..Our methodology should be applicable to other screens, and the suppressor and enhancer genes we identified may open new lines of research into mitosis and checkpoint biology...
  4. pmc The proliferation rate paradox in antimitotic chemotherapy
    Timothy J Mitchison
    Department of Systems Biology, Harvard Medical School, Boston, MA 02115, USA
    Mol Biol Cell 23:1-6. 2012
    ..Testing these potential mechanisms of drug action will facilitate rational improvement of antimitotic chemotherapy and perhaps cytotoxic chemotherapy more generally...
  5. pmc Rapid de-localization of actin leading edge components with BDM treatment
    Justin C Yarrow
    Dept of Cell Biology, Harvard Medical School, 240 Longwood Ave, Boston, MA 02115, USA
    BMC Cell Biol 4:5. 2003
    ..Recent reports show that BDM does not inhibit any non-muscle myosins so far tested, including nm-myosinII, prompting the question, how were these process affected in BDM studies?..
  6. pmc A high-throughput cell migration assay using scratch wound healing, a comparison of image-based readout methods
    Justin C Yarrow
    Department of Systems Biology, Institute of Chemistry and Cell Biology, Harvard Medical School, Boston, MA 02115, USA
    BMC Biotechnol 4:21. 2004
    ..Current migration assays for screening small molecules, siRNAs, or other perturbations are difficult to perform in parallel at the scale required to screen large libraries...
  7. pmc Mechanism and function of poleward flux in Xenopus extract meiotic spindles
    T J Mitchison
    Department of Systems Biology, Harvard Medical School, Boston, MA, USA
    Philos Trans R Soc Lond B Biol Sci 360:623-9. 2005
    ..By pulling microtubules through attachment sites at kinetochores, flux may generate poleward force on metaphase chromosomes...
  8. pmc Roles of polymerization dynamics, opposed motors, and a tensile element in governing the length of Xenopus extract meiotic spindles
    T J Mitchison
    Marine Biological Laboratory, Woods Hole, MA 02543, USA
    Mol Biol Cell 16:3064-76. 2005
    ..The response to microtubule destabilization suggests that an unidentified tensile element acts in parallel with these conventional factors, generating spindle shortening force...
  9. ncbi request reprint Small-molecule screening and profiling by using automated microscopy
    Timothy J Mitchison
    Dept Systems Biology and Institute of Chemistry and Cell Biology, Harvard Medical School, Boston, MA 02115, USA
    Chembiochem 6:33-9. 2005
    ..I discuss an example in which 100 small molecules with known bioactivity were profiled by using multiple fluorescent probes, and clustered into mechanistic classes by automated statistical analysis...
  10. pmc Bipolarization and poleward flux correlate during Xenopus extract spindle assembly
    T J Mitchison
    Cell Division Group, Marine Biological Laboratory, Woods Hole, MA 02543, USA
    Mol Biol Cell 15:5603-15. 2004
    ..Our results highlight the importance of two processes, chromatin-initiated microtubule nucleation, and sliding forces generated between antiparallel microtubules, in self-organization of spindle bipolarity and poleward flux...
  11. ncbi request reprint Mitosis: a history of division
    T J Mitchison
    Deparment of Cell Biology, Harvard Medical School, Boston, Massachusetts, USA
    Nat Cell Biol 3:E17-21. 2001
    ..Here we present a personal view of how far we have come, and where we need to go to fully understand the mechanisms involved in mitosis...
  12. pmc Anillin binds nonmuscle myosin II and regulates the contractile ring
    Aaron F Straight
    Department of Biochemistry, Stanford University School of Medicine, Stanford, CA 94305, USA
    Mol Biol Cell 16:193-201. 2005
    ..We propose a role for anillin in spatially regulating the contractile activity of myosin II during cytokinesis...
  13. pmc Direct observation of microtubule dynamics at kinetochores in Xenopus extract spindles: implications for spindle mechanics
    Paul Maddox
    Cell Division Group, Marine Biological Laboratory, Woods Hole, MA 02543, USA
    J Cell Biol 162:377-82. 2003
    ..These results provide the most complete description of spindle microtubule poleward flux to date, with important implications for the microtubule-kinetochore interface and for how flux regulates kinetochore function...
  14. ncbi request reprint Eg5 causes elongation of meiotic spindles when flux-associated microtubule depolymerization is blocked
    Mimi Shirasu-Hiza
    Department of Microbiology and Immunology, Stanford University, Stanford, CA 94305, USA
    Curr Biol 14:1941-5. 2004
    ..These results suggest that Eg5 is responsible for flux-associated MT translocation and that dynein and Xklp2 regulate flux-associated microtubule depolymerization at spindle poles...
  15. pmc NuSAP, a mitotic RanGTP target that stabilizes and cross-links microtubules
    Katharina Ribbeck
    European Molecular Biology Laboratory, D 69117 Heidelberg, Germany
    Mol Biol Cell 17:2646-60. 2006
    ..Once activated, NuSAP may aid to maintain spindle integrity by stabilizing and cross-linking microtubules around chromatin...
  16. pmc Spindle fusion requires dynein-mediated sliding of oppositely oriented microtubules
    Jesse C Gatlin
    Marine Biological Laboratory, Woods Hole, MA 02543, USA
    Curr Biol 19:287-96. 2009
    ..To study the underlying mechanisms responsible for spindle assembly and steady-state maintenance, we used microneedle manipulation of preassembled spindles in Xenopus egg extracts...
  17. ncbi request reprint A small-molecule inhibitor of Mps1 blocks the spindle-checkpoint response to a lack of tension on mitotic chromosomes
    Russell K Dorer
    Department of Molecular and Cellular Biology, Harvard University, Cambridge, Massachusetts 02138, USA
    Curr Biol 15:1070-6. 2005
    ..Our results demonstrate that Mps1 can be exploited as a target and that inhibiting the tension-sensitive branch of the spindle checkpoint may be a way of selectively killing cancer cells that display chromosomal instability...
  18. pmc Structural plasticity in actin and tubulin polymer dynamics
    Hao Yuan Kueh
    Department of Systems Biology, Harvard Medical School, Boston, MA 02215, USA
    Science 325:960-3. 2009
    ..We refer to these phenomena as "structural plasticity" and discuss emerging evidence that they play a central role in polymer dynamics and function...
  19. ncbi request reprint Rate-limiting guanosine 5'-triphosphate hydrolysis during nucleotide turnover by FtsZ, a prokaryotic tubulin homologue involved in bacterial cell division
    Laura Romberg
    Department of Cell Biology, Harvard Medical School, 250 Longwood Avenue, Boston, MA 02115, USA
    Biochemistry 43:282-8. 2004
    ..These results clarify previously conflicting results in the literature and suggest that pure FtsZ polymers, unlike microtubules, may not be able to undergo dynamic instability or to store energy in the polymer for force production...
  20. pmc Actin disassembly by cofilin, coronin, and Aip1 occurs in bursts and is inhibited by barbed-end cappers
    Hao Yuan Kueh
    Department of Systems Biology, Harvard Medical School, Boston, MA 02115, USA
    J Cell Biol 182:341-53. 2008
    ..The differential effects of drugs in cells argue for physiological relevance of this new disassembly pathway and potentially explain discordant results previously found with these drugs...
  21. ncbi request reprint Multidimensional drug profiling by automated microscopy
    Zachary E Perlman
    Institute of Chemistry and Cell Biology, Harvard Medical School, Boston, MA 02115, USA
    Science 306:1194-8. 2004
    ..Our methods will be useful for discovering the mechanism and predicting the toxicity of new drugs...
  22. ncbi request reprint Symmetry of septin hourglass and ring structures
    Alina M Vrabioiu
    Department of Systems Biology, Harvard Medical School, 200 Longwood Avenue, Boston, MA 02115, USA
    J Mol Biol 372:37-49. 2007
    ..We discuss possible anisotropic processes that could break the septin symmetry and establish the essential bud-neck asymmetry...
  23. pmc Binding partner switching on microtubules and aurora-B in the mitosis to cytokinesis transition
    Nurhan Ozlu
    Department of Systems Biology, Harvard Medical School, Boston, Massachusetts 02115, USA
    Mol Cell Proteomics 9:336-50. 2010
    ..Concretely, we report a central role for Aurora-B in regulating the C phase cytoskeleton...
  24. ncbi request reprint Poleward microtubule flux is a major component of spindle dynamics and anaphase a in mitotic Drosophila embryos
    Paul Maddox
    The Cell Division Group, Marine Biological Laboratory, Woods Hole, MA 02543, USA
    Curr Biol 12:1670-4. 2002
    ....
  25. ncbi request reprint Integrating high-content screening and ligand-target prediction to identify mechanism of action
    Daniel W Young
    Developmental and Molecular Pathways, Novartis Institutes for BioMedical Research, 250 Massachusetts Avenue, Cambridge, Massachusetts 02139, USA
    Nat Chem Biol 4:59-68. 2008
    ..By integrating these different descriptors of measured and potential biological activity, we can effectively draw mechanism-of-action inferences...
  26. ncbi request reprint Determining the position of the cell division plane
    Julie C Canman
    University of North Carolina, Department of Biology, 607 Fordham Hall, CB 3280, Chapel Hill, North Carolina 27699 3280, USA
    Nature 424:1074-8. 2003
    ..Our data are consistent with a model in which chromosomes supply microtubules with factors that promote microtubule stability and furrowing...
  27. ncbi request reprint Kinetic mechanism of blebbistatin inhibition of nonmuscle myosin IIb
    Bhagavathi Ramamurthy
    Department of Physiology, University of Pennsylvania School of Medicine, 3700 Hamilton Walk, Philadelphia, Pennsylvania 19104 6085, USA
    Biochemistry 43:14832-9. 2004
    ..These effects are likely mediated by binding of blebbistatin within the myosin cleft that progressively closes in forming the acto-myosin rigor state...
  28. pmc Dynamic stabilization of actin filaments
    Hao Yuan Kueh
    Department of Systems Biology, Harvard Medical School, 200 Longwood Avenue, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 105:16531-6. 2008
    ..Our results suggest that plasticity in the internal structure of the actin filament may play a fundamental role in regulating actin dynamics and may help cells build actin assemblies with vastly different turnover rates...
  29. ncbi request reprint A novel action of histone deacetylase inhibitors in a protein aggresome disease model
    Lisa J Corcoran
    Institute of Chemistry and Cell Biology, Harvard Medical School, Boston, MA 02115, USA
    Curr Biol 14:488-92. 2004
    ..Our findings suggest a connection between HDAC activity and aggresome formation and also lay the groundwork for a direct test of the role of aggresome formation in ALS etiology...
  30. ncbi request reprint Slide-and-cluster models for spindle assembly
    Kendra S Burbank
    Department of Physics, Harvard University, 17 Oxford Street, Cambridge, Massachusetts 02140, USA
    Curr Biol 17:1373-83. 2007
    ..This work demonstrates how the interplay between two types of motors together with continual nucleation of MTs by chromosomes could organize the MTs into spindles...
  31. ncbi request reprint The microtubule-destabilizing kinesin XKCM1 is required for chromosome positioning during spindle assembly
    Claire E Walczak
    Medical Sciences, Indiana University, Bloomington, IN 47405, USA
    Curr Biol 12:1885-9. 2002
    ..These results suggest that centromere bound XKCM1 has an important role in chromosome positioning on the spindle...
  32. pmc Exo1: a new chemical inhibitor of the exocytic pathway
    Yan Feng
    Institute of Chemistry and Cell Biology, Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 100:6469-74. 2003
    ..Thus, Exo1 allows the fatty acid exchange activity of Bars50 to be distinguished from ARF1 activity in the control of Golgi tubulation...
  33. pmc Quantitative live imaging of cancer and normal cells treated with Kinesin-5 inhibitors indicates significant differences in phenotypic responses and cell fate
    James D Orth
    Department of Systems Biology, Harvard Medical School, 200 Longwood Avenue, Boston, MA 02115, USA
    Mol Cancer Ther 7:3480-9. 2008
    ..Our analysis shows that K5Is cause cancer-selective cell killing, provides important kinetic information for understanding clinical responses, and elucidates mechanisms of drug sensitivity versus resistance at the level of phenotype...
  34. ncbi request reprint Nonredundant functions of Kinesin-13s during meiotic spindle assembly
    Ryoma Ohi
    Department of Systems Biology, Harvard Medical School, Boston, Massachusetts 02115, USA
    Curr Biol 17:953-9. 2007
    ..Rather, MCAK, but not XKIF2, plays a central role in regulating dynamic instability of plus ends and controls spindle length by that mechanism...
  35. ncbi request reprint XRHAMM functions in ran-dependent microtubule nucleation and pole formation during anastral spindle assembly
    Aaron C Groen
    Department of Systems Biology, Harvard Medical School, Boston, MA 02115, USA
    Curr Biol 14:1801-11. 2004
    ..Depending on cell type, microtubules nucleate through two different pathways: centrosome-driven or chromatin-driven. The chromatin-driven pathway dominates in cells lacking centrosomes...
  36. pmc Life and times of a cellular bleb
    Guillaume T Charras
    Department of Systems Biology, Harvard Medical School, Boston, Massachusetts, USA
    Biophys J 94:1836-53. 2008
    ..Finally, using artificially nucleated blebs as pressure sensors, we show that cells rounded up in mitosis possess a substantial intracellular pressure...
  37. pmc Differentiation of cytoplasmic and meiotic spindle assembly MCAK functions by Aurora B-dependent phosphorylation
    Ryoma Ohi
    Department of Systems Biology, Harvard Medical School, Boston, Massachusetts 02115, USA
    Mol Biol Cell 15:2895-906. 2004
    ....
  38. pmc A chemical method for fast and sensitive detection of DNA synthesis in vivo
    Adrian Salic
    Department of Cell Biology, Harvard Medical School, 240 Longwood Avenue, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 105:2415-20. 2008
    ..In contrast to BrdU, the method does not require sample fixation or DNA denaturation and permits good structural preservation. We demonstrate the use of the method in cultured cells and in the intestine and brain of whole animals...
  39. pmc Spatial patterning of metabolism by mitochondria, oxygen, and energy sinks in a model cytoplasm
    Philipp Niethammer
    Department of Systems Biology, Harvard Medical School, Boston, Massachusetts 02115, USA
    Curr Biol 18:586-91. 2008
    ....
  40. pmc Cell polarization during monopolar cytokinesis
    Chi Kuo Hu
    Department of Systems Biology, Harvard Medical School, Boston, MA 02115, USA
    J Cell Biol 181:195-202. 2008
    ..We propose that feedback loops between cortical furrow components and microtubules promote symmetry breaking during monopolar cytokinesis and regional specialization of the cytoskeleton during normal bipolar cytokinesis...
  41. pmc A novel small-molecule inhibitor reveals a possible role of kinesin-5 in anastral spindle-pole assembly
    Aaron C Groen
    Harvard Medical School, Department of Systems Biology, Boston, MA 02115, USA
    J Cell Sci 121:2293-300. 2008
    ..We also found that the spindle-pole proteins TPX2 and gamma-tubulin became redistributed to the spindle equator, suggesting that proper kinesin-5 function is required for pole assembly...
  42. pmc Microtubule plus-end dynamics in Xenopus egg extract spindles
    Jennifer S Tirnauer
    Woods Hole Marine Biological Laboratory, Woods Hole, Massachusetts 02543, USA
    Mol Biol Cell 15:1776-84. 2004
    ..These measurements move us closer to understanding the complete life history of a spindle microtubule...
  43. ncbi request reprint The majority of the Saccharomyces cerevisiae septin complexes do not exchange guanine nucleotides
    Alina M Vrabioiu
    Department of Systems Biology, Harvard University, Boston, MA 02115, USA
    J Biol Chem 279:3111-8. 2004
    ..We conclude that bound GTP and GDP play a structural, rather then regulatory, role for the majority of septins in proliferating cells as GTP does for alpha-tubulin...
  44. doi request reprint Mitosis: new roles for myosin-X and actin at the spindle
    Martin Wühr
    Department of Systems Biology, Harvard Medical School, Boston, Massachusetts 02115, USA
    Curr Biol 18:R912-4. 2008
    ....
  45. pmc Fascin-mediated propulsion of Listeria monocytogenes independent of frequent nucleation by the Arp2/3 complex
    William M Brieher
    Dept of Systems Biology, Harvard University Medical School, 250 Longwood Ave, SGM 523, Boston, MA 02115, USA
    J Cell Biol 165:233-42. 2004
    ..The biochemical and structural differences between the two motility reactions imply that each operates through distinct biochemical and biophysical mechanisms...
  46. pmc Functional overlap of microtubule assembly factors in chromatin-promoted spindle assembly
    Aaron C Groen
    Systems Biology Department, Harvard Medical School, Boston, MA 02445, USA
    Mol Biol Cell 20:2766-73. 2009
    ..These data reveal functional redundancy between specific assembly factors in the chromatin pathway, suggesting individual proteins or pathways commonly viewed to be essential may not have entirely unique functions...
  47. pmc A tissue-scale gradient of hydrogen peroxide mediates rapid wound detection in zebrafish
    Philipp Niethammer
    Department of Systems Biology, Harvard Medical School, Boston, Massachusetts 02114, USA
    Nature 459:996-9. 2009
    ..This is the first observation, to our knowledge, of a tissue-scale H(2)O(2) pattern, and the first evidence that H(2)O(2) signals to leukocytes in tissues, in addition to its known antiseptic role...
  48. pmc Pin-hole array correlation imaging: highly parallel fluorescence correlation spectroscopy
    Daniel J Needleman
    Department of Systems Biology, Harvard Medical School, Boston, Massachusetts, USA
    Biophys J 96:5050-9. 2009
    ....
  49. pmc Compression regulates mitotic spindle length by a mechanochemical switch at the poles
    Sophie Dumont
    Department of Systems Biology, Harvard Medical School, Boston, MA 02115, USA
    Curr Biol 19:1086-95. 2009
    ....
  50. ncbi request reprint An inner centromere protein that stimulates the microtubule depolymerizing activity of a KinI kinesin
    Ryoma Ohi
    Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA
    Dev Cell 5:309-21. 2003
    ..At inner centromeres, MCAK-ICIS may destabilize these microtubules and provide a mechanism that prevents kinetochore-microtubule attachment errors...
  51. pmc Evidence that mitotic exit is a better cancer therapeutic target than spindle assembly
    Hsiao Chun Huang
    Department of Systems Biology, Harvard Medical School, Boston, MA 02215, USA
    Cancer Cell 16:347-58. 2009
    ..We conclude targeting Cdc20, or otherwise blocking mitotic exit, may be a better cancer therapeutic strategy than perturbing spindle assembly...
  52. ncbi request reprint Small molecules, big impact: a history of chemical inhibitors and the cytoskeleton
    Jeffrey R Peterson
    Department of Cell Biology and Institute of Chemistry and Cell Biology, Harvard Medical School, Boston, MA 02115, USA
    Chem Biol 9:1275-85. 2002
    ..We then highlight several new inhibitors and the targeted screens used to identify them and discuss why this approach has been successful...
  53. pmc Force and length in the mitotic spindle
    Sophie Dumont
    Department of Systems Biology, Harvard Medical School, Boston, MA 02115, USA
    Curr Biol 19:R749-61. 2009
    ..We then discuss models for force integration and spindle length determination. We also emphasize key missing data that notably include absolute values of forces and how they vary as a function of position within the spindle...
  54. ncbi request reprint Evidence that monastrol is an allosteric inhibitor of the mitotic kinesin Eg5
    Zoltan Maliga
    Program in Biophysics, Harvard University, Boston, MA 02115, USA
    Chem Biol 9:989-96. 2002
    ..Future structural studies should help in designing more potent Eg5 inhibitors for possible use as anticancer drugs and cell biological reagents...
  55. ncbi request reprint Single-molecule speckle analysis of actin filament turnover in lamellipodia
    Naoki Watanabe
    Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA
    Science 295:1083-6. 2002
    ..Most of the actin filaments in the lamellipodium were generated by polymerization away from the tip...
  56. ncbi request reprint Dissecting temporal and spatial control of cytokinesis with a myosin II Inhibitor
    Aaron F Straight
    Department of Cell Biology and Institute of Chemistry and Cell Biology, Harvard Medical School, 250 Longwood Avenue, Boston, MA 02115, USA
    Science 299:1743-7. 2003
    ..Continuous signals from microtubules are required to maintain the position of the cleavage furrow, and these signals control the localization of myosin II independently of other furrow components...
  57. ncbi request reprint Tankyrase-1 polymerization of poly(ADP-ribose) is required for spindle structure and function
    Paul Chang
    Department of Systems Biology, Harvard Medical School, Boston, MA 02115, USA
    Nat Cell Biol 7:1133-9. 2005
    ..We also demonstrate a requirement for tankyrase-1 in the assembly of bipolar spindles, and identify the spindle-pole protein NuMA as a substrate for covalent modification by tankyrase-1...
  58. pmc EB1 targets to kinetochores with attached, polymerizing microtubules
    Jennifer S Tirnauer
    Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115, USA
    Mol Biol Cell 13:4308-16. 2002
    ..Our results suggest EB1 may modulate kinetochore microtubule polymerization and/or attachment...
  59. ncbi request reprint Self- and actin-templated assembly of Mammalian septins
    Makoto Kinoshita
    Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA
    Dev Cell 3:791-802. 2002
    ..We conclude that septins alone self-assemble into rings, that adaptor proteins recruit septins to actin bundles, and that septins help organize these bundles...
  60. pmc Parallel chemical genetic and genome-wide RNAi screens identify cytokinesis inhibitors and targets
    Ulrike S Eggert
    Department of Systems Biology, Harvard Medical School Boston, Massachusetts, USA
    PLoS Biol 2:e379. 2004
    ..Our study shows that parallel RNA interference and small molecule screening is a generally useful approach to identifying active small molecules and their target pathways...
  61. ncbi request reprint High-content screening and profiling of drug activity in an automated centrosome-duplication assay
    Zachary E Perlman
    Department of Systems Biology and Institute for Chemistry and Cell Biology, Harvard Medical School, Boston, MA 02115, USA
    Chembiochem 6:145-51. 2005
    ..The analysis methodology reported here is directly relevant to studies of centrosome regulation in a variety of systems and is adaptable to a wide range of other biological problems...
  62. ncbi request reprint Poly(ADP-ribose) is required for spindle assembly and structure
    Paul Chang
    Department of Systems Biology, Harvard Medical School, Boston, Massachusetts 02115, USA
    Nature 432:645-9. 2004
    ..Thus, PAR is a non-proteinaceous, non-chromosomal component of the spindle required for bipolar spindle assembly and function...
  63. pmc The kinesin Eg5 drives poleward microtubule flux in Xenopus laevis egg extract spindles
    David T Miyamoto
    Department of Systems Biology, Harvard Medical School, Boston, MA 02115, USA
    J Cell Biol 167:813-8. 2004
    ..Our results suggest that ensembles of nonprocessive Eg5 motors drive flux in metaphase Xenopus extract spindles...
  64. ncbi request reprint Vertebrate shugoshin links sister centromere cohesion and kinetochore microtubule stability in mitosis
    Adrian Salic
    Department of Systems Biology, 240 Longwood Avenue, Boston, MA 02115, USA
    Cell 118:567-78. 2004
    ..Sgo is thus critical for mitotic progression and chromosome segregation and provides an unexpected link between sister centromere cohesion and microtubule interactions at kinetochores...
  65. ncbi request reprint Screening for cell migration inhibitors via automated microscopy reveals a Rho-kinase inhibitor
    Justin C Yarrow
    Department of Systems Biology, Boston, Massachusetts 02115, USA
    Chem Biol 12:385-95. 2005
    ..We also profile the wound healing assay with a library of compounds with known bioactivities, revealing multiple pathways involved in the biology...
  66. pmc EB1-microtubule interactions in Xenopus egg extracts: role of EB1 in microtubule stabilization and mechanisms of targeting to microtubules
    Jennifer S Tirnauer
    Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115, USA
    Mol Biol Cell 13:3614-26. 2002
    ....
  67. ncbi request reprint Synthesis and phenotypic screening of a Guanine-mimetic library
    Stephen C Miller
    Department of Cell Biology and Institute of Chemistry and Cell Biology, Harvard Medical School, Boston, MA 02115, USA
    Chembiochem 5:1010-2. 2004
  68. ncbi request reprint Structural insights into yeast septin organization from polarized fluorescence microscopy
    Alina M Vrabioiu
    Department of Systems Biology, Harvard Medical School, 200 Longwood Avenue, Boston, Massachusetts 02115, USA
    Nature 443:466-9. 2006
    ..These data resolve a long-standing controversy in the field and provide strong evidence that septins have a mechanical function in cell division...
  69. pmc Reassembly of contractile actin cortex in cell blebs
    Guillaume T Charras
    Department of Systems Biology, Harvard Medical School, Boston, MA 02115, USA
    J Cell Biol 175:477-90. 2006
    ..Ezrin played no role in actin nucleation, but was essential for tethering the membrane to the cortex. The Rho pathway was important for cortex assembly in blebs...
  70. pmc A new method reveals microtubule minus ends throughout the meiotic spindle
    Kendra S Burbank
    Department of Physics, Harvard University, Cambridge, MA 03138, USA
    J Cell Biol 175:369-75. 2006
    ....
  71. ncbi request reprint Meiotic spindle: sculpted by severing
    Katharina Ribbeck
    Systems Biology, Harvard Medical School, Boston, Massachusetts 02115, USA
    Curr Biol 16:R923-5. 2006
    ..A recent study using electron tomography has found that katanin stimulates the production of microtubules in the meiotic spindles of Caenorhabditis elegans oocytes...
  72. pmc Rapid actin monomer-insensitive depolymerization of Listeria actin comet tails by cofilin, coronin, and Aip1
    William M Brieher
    Department of Systems Biology and 2Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA
    J Cell Biol 175:315-24. 2006
    ..The cooperative activities of cofilin, coronin, and Aip1 should provide a biochemical basis for understanding how actin filaments can grow in some places in the cell while shrinking in others...
  73. ncbi request reprint Small molecule screening by imaging
    Ulrike S Eggert
    Department of Systems Biology, Harvard Medical School, Boston, MA 02115, USA
    Curr Opin Chem Biol 10:232-7. 2006
    ..We discuss the use of model organisms such as zebrafish in screens and review different methods of target identification. The emerging field of automated image analysis is also introduced...
  74. ncbi request reprint Small molecules in an RNAi world
    Ulrike S Eggert
    Department of Systems Biology, Harvard Medical School, Boston, MA 02115, USA
    Mol Biosyst 2:93-6. 2006
    ..In this Opinion, we compare and contrast small molecules and RNAi. We discuss the advantages and disadvantages of both technologies focusing on timing, specificity, dose and therapeutic use...
  75. ncbi request reprint Microtubule dynamic instability
    Kendra S Burbank
    Department of Physics, Harvard University, Cambridge, Massachusetts 02115, USA
    Curr Biol 16:R516-7. 2006
  76. ncbi request reprint Animal cytokinesis: from parts list to mechanisms
    Ulrike S Eggert
    Dana Farber Cancer Institute and Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts 02115, USA
    Annu Rev Biochem 75:543-66. 2006
    ..We also discuss the extent to which classic questions have been answered and identify major outstanding questions...
  77. pmc Polar stimulation and constrained cell migration in microfluidic channels
    Daniel Irimia
    BioMEMS Resource Center, Center for Engineering in Medicine and Surgical Services, Massachusetts General Hospital, Shriners Hospital for Children, and Harvard Medical School, Boston, MA, USA
    Lab Chip 7:1783-90. 2007
    ..The microchannels constrain cell morphology and induce qualitative and quantitative changes in neutrophil chemotaxis that mimic cells crawling through tissues...
  78. pmc Targeting cell division: small-molecule inhibitors of FtsZ GTPase perturb cytokinetic ring assembly and induce bacterial lethality
    Danielle N Margalit
    Institute of Chemistry and Cell Biology, Harvard Medical School, 250 Longwood Avenue, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 101:11821-6. 2004
    ..Our results illustrate the utility of small-molecule chemical probes to study FtsZ polymerization dynamics and the feasibility of FtsZ as a novel therapeutic target...
  79. ncbi request reprint Chemical inhibitor of nonapoptotic cell death with therapeutic potential for ischemic brain injury
    Alexei Degterev
    Department of Cell Biology, Harvard Medical School, 240 Longwood Avenue, Boston, Massachusetts 02115, USA
    Nat Chem Biol 1:112-9. 2005
    ..Our study identifies a previously undescribed basic cell-death pathway with potentially broad relevance to human pathologies...
  80. ncbi request reprint Cytoskeleton: what does GTP do for septins?
    Timothy J Mitchison
    Department of Cell Biology, Harvard Medical School, 240 Longwood Avenue, Boston, MA 02115 5731, USA
    Curr Biol 12:R788-90. 2002
    ..This model cannot, however, explain the GTP-biochemistry of heteromeric septin complexes from cytosol...
  81. ncbi request reprint Dynamics of the mitotic spindle--potential therapeutic targets
    David T Miyamoto
    Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA
    Prog Cell Cycle Res 5:349-60. 2003
    ..We review in depth a number of proteins of particular interest, highlighting their known functions in mitosis and the effects of their inhibition on cell cycle progression...
  82. pmc Evidence for an upper limit to mitotic spindle length
    Martin Wühr
    Department of Systems Biology, Harvard Medical School, Boston, Massachusetts 02115, USA
    Curr Biol 18:1256-61. 2008
    ..We conclude that early mitotic spindle length in Xenopus laevis is uncoupled from cell length, reaching an upper bound determined by mechanisms that are intrinsic to the spindle...
  83. ncbi request reprint Involvement of the ubiquitin-proteasome system in the early stages of wallerian degeneration
    Qiwei Zhai
    Division of Neuroscience, Children s Hospital, Harvard Medical School, Boston, MA 02115, USA
    Neuron 39:217-25. 2003
    ..Our findings suggest a possibility that inhibiting UPS activity may serve to retard axon degeneration in pathological conditions...
  84. pmc Chemical genetics to identify NFAT inhibitors: potential of targeting calcium mobilization in immunosuppression
    Natarajan Venkatesh
    Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 101:8969-74. 2004
    ....
  85. pmc Growth, interaction, and positioning of microtubule asters in extremely large vertebrate embryo cells
    Timothy Mitchison
    Department of Systems Biology, Harvard Medical School and Marine Biological Laboratory, Woods Hole, Massachusetts, USA
    Cytoskeleton (Hoboken) 69:738-50. 2012
    ..Studying these problems in extremely large cells is starting to reveal how general principles of cell organization scale with cell size...
  86. ncbi request reprint Caspase-11 regulates cell migration by promoting Aip1-Cofilin-mediated actin depolymerization
    Juying Li
    Department of Cell Biology, Harvard Medical School, 240 Longwood Ave, Boston, MA 02115, USA
    Nat Cell Biol 9:276-86. 2007
    ..These data demonstrate a novel cell autonomous caspase-mediated mechanism that regulates actin dynamics and mammalian cell migration distinct from the receptor mediated Rho-Rac-Cdc42 pathway...

Research Grants4

  1. ELECTRON MICROSCOPE
    Timothy Mitchison; Fiscal Year: 2004
    ..The automated controls and digital image acquisition will also be optimal for introducing new users to electron microscopy and for minimizing maintenance requirements that might arise from operator inexperience. ..
  2. ACTIN DYNAMICS AND CELL LOCOMOTION
    Timothy Mitchison; Fiscal Year: 2004
    ..For perturbation experiments we will use protein tools, and also cell permeable chemicals coming out of a screening effort at the Harvard Institute of Chemistry and Cell Biology (ICCB). ..
  3. Probing Cell Division with Synthetic Chemistry
    Timothy Mitchison; Fiscal Year: 2008
    ..Having found small molecule tools that perturb cell division by novel mechanisms, we will test their ability to kill cancer cells in vitro. ..
  4. Cytoskeleton polymerization dynamics in the cell cycle
    Timothy J Mitchison; Fiscal Year: 2010
    ..Understanding midbody assembles will reveal principles for generating asymmetric assemblies in the cytoplasm, and will tell us how the cleavage furrow is positioned. ..