Browsing by Author "Mitchison, Timothy"
Now showing items 1-20 of 25
-
Actin Disassembly by Cofilin, Coronin, and Aip1 Occurs in Bursts and Is Inhibited by Barbed-end Cappers
Kueh, Hao Yuan; Charras, Guillaume T.; Mitchison, Timothy J.; Brieher, William M. (The Rockefeller University Press, 2008)Turnover of actin filaments in cells requires rapid actin disassembly in a cytoplasmic environment that thermodynamically favors assembly because of high concentrations of polymerizable monomers. We here image the disassembly ... -
Assembly and Regulation of the Inflammasome Governed by a Unified Polymerization Mechanism
Lu, Alvin Z. (2016-05-13)The innate immune system employs a diverse set of pattern recognition receptors to detect intrinsic and extrinsic danger signals for host protection. Inflammasomes represent an important class of receptors that elicit ... -
The Atg1-Tor Pathway Regulates Yolk Catabolism in Drosophila Embryos
Kuhn, Hallie; Sopko, Richelle; Coughlin, Margaret; Perrimon, Norbert; Mitchison, Timothy (The Company of Biologists, 2015-11-15)Yolk provides an important source of nutrients during the early development of oviparous organisms. It is composed mainly of vitellogenin proteins packed into membrane-bound compartments called yolk platelets. Catabolism ... -
Computational imaging reveals mitochondrial morphology as a biomarker of cancer phenotype and drug response
Giedt, Randy J.; Fumene Feruglio, Paolo; Pathania, Divya; Yang, Katherine S.; Kilcoyne, Aoife; Vinegoni, Claudio; Mitchison, Timothy J.; Weissleder, Ralph (Nature Publishing Group, 2016)Mitochondria, which are essential organelles in resting and replicating cells, can vary in number, mass and shape. Past research has primarily focused on short-term molecular mechanisms underlying fission/fusion. Less is ... -
The Development of Chemical and Computational Tools to Study Transcriptional Regulation in Cancer
Federation, Alexander Joel (2015-05-01)Eukaryotic gene regulation is a complex process requiring the action of many multicomponent complexes in the cell. Specific inhibitors of chromatin-associated factors allow the functional study of protein domains without ... -
Directly Probing the Mechanical Properties of the Spindle and Its Matrix
Gatlin, Jesse C.; Matov, Alexandre; Danuser, Gaudenz; Mitchison, Timothy J.; Salmon, Edward D. (The Rockefeller University Press, 2010)Several recent models for spindle length regulation propose an elastic pole to pole spindle matrix that is sufficiently strong to bear or antagonize forces generated by microtubules and microtubule motors. We tested this ... -
Experimental and Computational Tools to Study P53 Dynamics at the Single-Cell Level
Karhohs, Kyle Wayne (2015-09-21)One of the most commonly mutated genes found in cancer is the tumor suppressor p53. p53 is a transcription factor capable of inducing cell-cycle arrest, apoptosis, senescence, and other cellular processes thought to halt ... -
Experiments and Analysis of Mitochondrial DNA Segregation, Yeast Polarization and RNA Polymerase Dynamics
Jajoo, Rishi Har (2015-03-27)This thesis presents work done in three different topics in biology with a combination of experiments, mathematical modeling and quantitative data analysis. All cellular materials are partitioned between daughters at cell ... -
A high-throughput cell migration assay using scratch wound healing, a comparison of image-based readout methods
Yarrow, Justin C; Perlman, Zachary E; Westwood, Nicholas J; Mitchison, Timothy J. (BioMed Central, 2004)Background: Cell migration is a complex phenomenon that requires the coordination of numerous cellular processes. Investigation of cell migration and its underlying biology is of interest to basic scientists and those in ... -
Hydrolysis of 2′3′-cGAMP by ENPP1 and design of non-hydrolyzable analogs
Li, Lingyin; Yin, Qian; Kuss, Pia; Maliga, Zoltan; Millán, José L.; Wu, Hao; Mitchison, Timothy J. (2014)Agonists of mouse STING (TMEM173) shrink and even cure solid tumor by activating innate immunity; human STING agonists are needed to test this therapeutic hypothesis in man. The endogenous STING agonist is 2′3′-cGAMP, a ... -
Identifying Mechanisms of Apoptotic Pore Formation With Programmatic Ensemble Modeling
Bachman, John (2016-02-05)Mitochondrial outer membrane permeabilization is a key step in the apoptotic cell death program, regulating life-death decisions in response to cytotoxic drugs and other forms of cell stress. In this thesis I use mathematical ... -
In search of breast cancer cell secretions with therapeutic and diagnostic value.
Georgoulia, Nefeli Eleonora (2014-06-06)The first end point of this study was to identify specific pro-apoptotic or anti-proliferative factors in the breast cancer cell secretome. To this end, we designed an in vitro screen that effectively cross-cultured 20 ... -
In vivo cell cycle profiling in xenograft tumors by quantitative intravital microscopy
Chittajallu, Deepak R; Florian, Stefan; Kohler, Rainer H; Iwamoto, Yoshiko; Orth, James D; Weissleder, Ralph; Danuser, Gaudenz; Mitchison, Timothy J (2015)Quantification of cell-cycle state at a single-cell level is essential to understand fundamental three-dimensional biological processes such as tissue development and cancer. Analysis of 3D in vivo images, however, is very ... -
An Intermittent Live Cell Imaging Screen for siRNA Enhancers and Suppressors of a Kinesin-5 Inhibitor
Tsui, Melody; Xie, Tiao; Orth, James Daniel; Carpenter, Anne E.; Rudnicki, Stewart; Kim, Suejong; Shamu, Caroline Elizabeth; Mitchison, Timothy J. (Public Library of Science, 2009)Kinesin-5 (also known as Eg5, KSP and Kif11) is required for assembly of a bipolar mitotic spindle. Small molecule inhibitors of Kinesin-5, developed as potential anti-cancer drugs, arrest cell in mitosis and promote ... -
IRF3 and type I interferons fuel a fatal response to myocardial infarction
King, Kevin R; Aguirre, Aaron Dominic; Ye, Yu-Xiang; Sun, Yuan; Roh, Jason David; Ng, Richard Patrick; Kohler, Rainer H.; Arlauckas, Sean Philip; Iwamoto, Yoshiko; Savol, Andrej J; Sadreyev, Ruslan; Kelly, Mark; Fitzgibbons, Timothy P; Fitzgerald, Katherine A; Mitchison, Timothy J.; Libby, Peter; Nahrendorf, Matthias; Weissleder, Ralph (Springer Nature, 2017)Interferon regulatory factor 3 (IRF3) and type I interferons (IFNs) protect against infections and cancer, but excessive IRF3 activation and type I IFN production cause autoinflammatory conditions such as Aicardi–Goutières ... -
MELK is an oncogenic kinase essential for mitotic progression in basal-like breast cancer cells
Wang, Yubao; Lee, Young-Mi; Baitsch, Lukas; Huang, Alan; Xiang, Yi; Tong, Haoxuan; Lako, Ana; Von, Thanh; Choi, Christine; Lim, Elgene; Min, Junxia; Li, Li; Stegmeier, Frank; Schlegel, Robert; Eck, Michael J; Gray, Nathanael S; Mitchison, Timothy J; Zhao, Jean J (eLife Sciences Publications, Ltd, 2014)Despite marked advances in breast cancer therapy, basal-like breast cancer (BBC), an aggressive subtype of breast cancer usually lacking estrogen and progesterone receptors, remains difficult to treat. In this study, we ... -
On the growth of microtubule asters spanning millimeter-sized cells
Ishihara, Keisuke (2016-01-12)The large cells in early vertebrate embryos are organized by radial arrays of microtubules called asters. Asters grow, interact, and move to precisely position the cleavage planes of for each cell division. Cell-spanning ... -
Pin-Hole Array Correlation Imaging: Highly Parallel Fluorescence Correlation Spectroscopy
Needleman, Daniel Joseph; Xu, Yangqing; Mitchison, Timothy J. (Elsevier, 2009)In this work, we describe pin-hole array correlation imaging, a multipoint version of fluorescence correlation spectroscopy, based upon a stationary Nipkow disk and a high-speed electron multiplying charged coupled detector. ... -
Rapid De-Localization of Actin Leading Edge Components with BDM Treatment
Yarrow, Justin C; Lechler, Terry; Li, Rong; Mitchison, Timothy J. (BioMed Central, 2003)Background: 2,3-Butanedione monoxime (BDM) has been widely used as a non-muscle myosin inhibitor to investigate the role of non-muscle myosinII in the process of actin retrograde flow and other actin cytoskeletal processes. ... -
Small-Molecule and Mutational Analysis of Allosteric Eg5 Inhibition by Monastrol
Maliga, Zoltan; Mitchison, Timothy J. (BioMed Central, 2006)Background: A recent crystal structure of monastrol in a ternary complex with the kinesin Eg5 motor domain highlights a novel, induced-fit drug binding site at atomic resolution. Mutational obliteration of the monastrol ...