- B.A., Physics, Brandeis University
- Ph.D., Physics, University of California, Santa Barbara
- Marriage of Biological & Artificial Systems
- Biomechanics and Motor Control
- Cell and Tissue Engineering and Biomaterials
- Materials & Devices
- Biophysics and Self-Assembly
- Materials Science
- Soft Condensed Matter
- Surface and Interface Science
Primary Teaching Area
The Needleman laboratory investigates how the cooperative behaviors of molecules give rise to the architecture and dynamics of self-organizing subcellular structures. These collective effects are not only directly relevant to cellular organization, they also raise a number of fascinating questions concerning the mechanics and statistical physics of these highly non-equilibrium systems. Our long term goal is to use our knowledge of subcellular structures to quantitatively predict biological behaviors and to determine if there are general principles which govern these non-equilibrium steady-state systems.
Our work currently focuses on studying the spindle, the self-organizing molecular machine that segregates chromosomes during cell division. The spindle is a dynamic steady-state structure composed of a plethora of molecules, most notably DNA, which is compacted into chromosomes, and the protein tubulin, which forms long fibers, called microtubules, which are oriented into a bipolar array that constitutes the bulk of the spindle. Even though the overall structure of the spindle can remain unchanged for hours, the molecules that make up the spindle undergo rapid turnover with a half-life of tens of seconds or less, and if the spindle is damaged, or even totally destroyed, it can repair itself. While many of the individual components of the spindle have been studied in detail, it is still unclear how these molecular constituents self-organize into this structure and how this leads to the internal balance of forces that are harnessed to divide the chromosomes.
Research in the Needleman laboratory uses three complementary approaches:
- We are using a range of methods, from single molecule tracking, to magnetic tweezers, to high resolution fluorescence and polarized light microscopy, to study microtubule nucleation, polymerization, and translocation throughout spindles, as well as the activity of motors and other proteins. These quantitative measurements are combined with biochemical and genetic perturbations, and theoretical analysis, to relate the underlying protein dynamics to spindle architecture and, finally, chromosome motion.
- We are developing novel experimental techniques to collect data that is currently inaccessible. This work includes the development of a massively parallel form of fluorescence correlation spectroscopy which will be able to measure the concentration, dynamics, and interactions of soluble proteins at hundreds of points in and around spindles. We are also working on new image analysis methods for optical and electron microscopy.
- We will study self-organization in simple model systems of highly purified cytoskeletal components designed to mimic specific aspects of spindle assembly. Experiments performed on in vitro systems reconstituted from purified components can be highly controlled and therefore provide the ability to test theories in a more rigorous manner than is possible in vivo.
- Danyiar Nurgaliev, Timur Gatanov, and Daniel J. Needleman, Automated Identification of Microtubules in Cellular Electron Tomography. Methods in Cell Biology, 2010, 97. PDF
- Leonid A. Mirny and Daniel J. Needleman, Quantitative Characterization of Filament Dynamics by Single-Molecule Lifetime Measurements. Methods in Cell Biology, 2010, 95. PDF
- Daniel J. Needleman and Reza Farhadifar, Mitosis: Taking the Measure of the Spindle Length. Current Biology, 2010, 20, 8 R360. PDF
- Jan Brugues and Daniel J. Needleman, Nonequilibrium Fluctuations in Metaphase Spindles: Polarized Light Microscopy, Image Registration, and Correlation Functions. Proc. SPIE , 2010, 7618. PDF
- Daniel J. Needleman, Aaron Groen, Ryoma Ohi, Leonid Mirny, Tim Mitchison, Fast Microtubule Dynamics in Meiotic Spindles Measured by Single Molecule Imaging: Evidence that the Spindle Environment does not Stabilize Microtubules. Molecular Biology of the Cell, 2010, 21, 323-333. PDF
- Daniel Needleman, Cellular Allometry: The Spindle in Development and Inheritance. Current Biology , 2009, 19, R846-R847. PDF
- Alexander F. Schier and Daniel Needleman, Rise of the Source-Sink Model. Nature , 2009, 2461, 480-481. PDF
- M.C. Choi, U. Raviv, H.P. Miller, M.R. Gaylord, E. Kiris, D. Ventimiglia, D.J. Needleman, M.W. Kim, L. Wilson, S.C. Feinstein, C.R. Safinya, Human Microtubule-Associated-Protein Tau Regulates the Number of Protofilaments in Microtubules: A Synchrotron X-Ray Scattering Study. Biophysical Journal , 2009, 97, 519-527. PDF
- Martin Wuhr, Sophie Dumont, Aaron C. Groen, Daniel J. Needleman, Tim Mitchison, How Does A Millimeter-Sized Cell Find Its Center? Cell Cycle , 2009, 8, 1115-1121. PDF
- Daniel J. Needleman, Yangqing Xu, Tim Mitchison, Pin-Hole Array Correlation Imaging: Highly Parallel Fluorescence Correlation Spectroscopy. Biophysical Journal, 2009, 96, 5050-5059. PDF
- Jesse C. Gatlin, Alexandre Matov, Aaron C. Groen, Daniel J. Needleman, Thomas J. Maresca, Gaudenz Danuser, Tim Mitchison, E.D. Salmon, Spindle Fusion Requires Dynein-Mediated Sliding of Oppositely Oriented Microtubules. Current Biology, 2009, 19, 287-296. PDF
- Martin Wuehr, Yao Chen, Sophie Dumont, Aaron Groen, Daniel J. Needleman, Adrian Salic, Timothy J. Mitchison, Evidence for an Upper Limit to Mitotic Spindle Length. Current Biology, 2008, 18, 1256-1261. PDF
- Aaron C. Groen, Daniel J. Needleman, Clifford Brangwynne, Christain Gradinaru, Brandon Fowler, Ralph Mazitschek, Timoth J. Mitchison, A Novel Small-Molecule Inhibitor Reveals a Possible Role of Kinesin-5 in Anastral Spindle-Pole Assembly. Journal of Cell Science, 2008, 121, 2293-2300. PDF
- Daniel J. Needleman, Plasmid Segregation: Is a Total Understanding within Reach? Current Biology, 2008, 18, R212-R214. PDF
- Uri Raviv, Daniel J, Needleman, Kai Ewert, Cyrus R. Safinya, Hierarchical Bionanotubes Formed by the Self Assembly of Microtubules with Cationic Membranes or Polypeptides. Journal of Applied Crystallography. 2007, 40, s83-s87. PDF
- Uri Raviv, Toan Nguyen, Rouzbeh Ghafouri, Daniel J, Needleman, Youli Li, Herbert P. Miller, Leslie Wilson, Robijn F. Bruinsma, Cyrus R. Safinya, Microtubule Protofilament Number is Modulated in a Step-Wise Fashion by the Charge Density of an Enveloping Layer. Biophysical Journal. 2007, 92, 278-287. PDF
- Cyrus R. Safinya, Kai Ewert, Ayesha Ahmad, Heather M. Evans, Uri Raviv, Daniel J. Needleman, Alison J. Lin, Nele L. Slack, Cyril George. Cationic Liposome-DNA Complexes: From Liquid Crystal Science to Gene Delivery Applications. Philosophical Transactions of the Royal Society A, 2006, 364, 2573-2596.
- Uri Raviv, Daniel J. Needleman, Cyrus R. Safinya, Cationic Membranes Complexed with Oppositely Charged Microtubules: Hierarchical Self-Assembly Leading to Bio-Nanotubes. Journal of Physics: Condensed Matter, 2006, 18, S1271-S1279. PDF
- Daniel J. Needleman, Jayna B. Jones, Uri Raviv, Miguel A. Ojeda-Lopez, Herbert P. Miller, Youli Li, Leslie Wilson, Cyrus R. Safinya, Supramolecular Assembly of Biological Molecules Purified from Bovine Nerve Cells: from Microtubule Bundles and Necklaces to Neurofilament Networks. Journal of Physics: Condensed Matter, 2005, 17, S3225-S3230. PDF
- Daniel J. Needleman, Miguel Ojeda-Lopez, Uri Raviv, Kai Ewert, Herbert P. Miller, Leslie Wilson, Cyrus R. Safinya, Radial Compression of Microtubules and the Mechanism of Action of Taxol and Associated Proteins. Biophysical Journal, 2005, 89, 3410-3423. PDF
- Uri Raviv, Daniel J. Needleman, Miguel Ojeda-Lopez, Herbert P. Miller, Leslie Wilson, Cyrus R. Safinya, Cationic Liposome-Microtubule Complexes: Pathways to the Formation of Two-State Lipid-Protein Nanotubes with Open or Closed Ends. Proceedings of the National Academy of Sciences, Track II, August 2005, 102, 11167-11172. PDF
- Daniel J. Needleman, Miguel Ojeda-Lopez, Uri Raviv, Herbert P. Miller, Leslie Wilson, Cyrus R. Safinya, Higher Order Assembly of Microtubules by Counter-ions: From Hexagonal Bundles to Living Necklaces. Proceedings of the National Academy of Sciences, Track II, November 2004, 101, 16099-16103. PDF
- Daniel J. Needleman, Miguel Ojeda-Lopez, Uri Raviv, Kai Ewert,
Jayna B. Jones, Herbert P. Miller, Leslie Wilson, Cyrus R. Safinya, Microtubule
Buckling and Bundling Under Osmotic Stress: A Synchrotron X-ray
Diffraction Study Probing Inter-Protofilament Interactions. Physical Review Letters, November 2004, 93, 198104.
- Deborah K. Fygenson, Daniel J. Needleman, Kim Sneppen, Variability Based Sequence Alignment Identifies Residues Responsible for Functional Differences in a and b Tubulin. Protein Science, January 2004, 13, 25-31
- Daniel J. Needleman, Paul Tiesinga, Terrence J. Sejnowski, Collective Enhancement of Precision in Networks of Coupled Oscillators. Physica D, July 2001, 155, 324-336
- Stephen Monks, Daniel J. Needleman, Christopher Miller, Helical Structure and Packing Orientation of the S2 Segment in the Shaker K+ Channel. Journal of General Physiology, March 1999, 113, 415-423