LBNL Masthead A-Z Index Berkeley Lab masthead U.S. Department of Energy logo Phone Book Jobs Search
homesearch for an expertcontact us

Berkeley Lab Experts
From accelerators to energy to supercomputers,
Berkeley Lab has a science expert for you.

background

Kenneth Downing

biophysicist: Biosciences

Media contact: Dan Krotz, (510) 486-4019, DAKrotz@lbl.gov

 

Kenneth’s research is directed toward understanding the processes that drive and regulate various subcellular processes, principally those that relate to microtubules.  Mainly using electron microscopy, tomography and crystallography, he and his team seek to understand the structure of the protein tubulin and explore its interactions with a wide range of drugs and other proteins.  Information they gain is vital to understanding the development of various subcellular structures and the movement of components within the cell.

Much of Kenneth’s lab’s activity focuses on the structure and function of tubulin, the main protein in microtubules.  Microtubules play a vital role in the life of all eukaryotic cells, as they are involved in organelle movement, separation of chromosomes during cell division, maintenance of cell shape and other critical cellular activities.  The assembly and disassembly of microtubules at particular times are essential steps in the cell cycle.  These processes are closely regulated, and interference with the regulatory mechanisms can lead to cell death.  These properties have made tubulin both a fascinating specimen for biophysical studies and a useful target for anti-cancer drugs. 

As a first step in understanding microtubule dynamics and their regulation, they have determined the structure of tubulin by electron crystallography.  The crystals used in this work contained the anti-cancer drug Taxol, which binds to tubulin and stabilizes microtubules. To complement the crystal structure, they used cryo-EM to determine the structure of intact microtubules at a resolution that allows very precise docking of the tubulin molecule. 

In further work, Kenneth’s lab is studying the interaction of tubulin with other drugs that stabilize microtubules and the interactions with some of the proteins that utilize and regulate the microtubule cytoskeleton.  They have determined the structure of the tubulin/epothilone-A complex and have preliminary data on several other drugs.  His lab has also obtained maps of kinesin-decorated microtubules at a resolution sufficient to see details of the conformational changes involved in kinesin’s binding onto microtubules and in its ATP hydrolysis cycle.  Electron tomography has now been used to study the structure of microtubule doublets and to understand the nature of some of their non-tubulin components.  This work is aimed at developing a rational understanding of the functional mechanisms of microtubule dynamics and protein interactions and may reveal the underlying mechanism of microtubule stabilization, eventually allowing development of new, more effective drugs targeted to tubulin.

Recent Publications

R. Henderson, A. Sali, M. L. Baker, B. Carragher, B. Devkota, K. H. Downing, E. H. Egelman, Z. Feng, J. Frank, N Grigorieff, W. Jiang, S. J. Ludtke, O. Medalia, P. A. Penczek2, P. B. Rosenthal, M. G. Rossmann, M. F. Schmid, G. F. Schröder, A. C. Steven, D. L. Stokes, J. D. Westbrook, W. Wriggers, H. Yang, J. Young, H. M. Berman, W. Chiu, G. J. Kleywegt and C. L. Lawson.   Outcome of the first electron microscopy validation task force meeting.   Structure 20, 205-14 (2012)

S. Yakovlev, N. P. Balsara and K. H. Downing.   Limits of spatial and compositional resolution of electron energy loss spectroscopy of soft materials.  Ultramicroscopy 116, 39-46 (2012)

H. Wang and K. H. Downing.   Specimen preparation for electron diffraction of thin crystals.  Micron 42, 132-40 (2011)

D. M. Larson, K. H. Downing and R. M. Glaeser.   The surface of evaporated carbon films is an insulating, high-bandgap material.  J. Struct. Biol. 174, 420-3 (2011)

S. Yakovlev and K. H. Downing.   Crystalline ice as a cryoprotectant: theoretical calculation of cooling speed in capillary tubes.  J. Microsc. 243, 8-14 (2011)

S. Yakovlev and K. H. Downing.  Self pressure freezing for the preparation of frozen hydrated sections.  J. Microsc. 244, 235-47 (2011)

S. Yakovlev, X. Wang, P. Ercius, N. P. Balsara and K. H. Downing.   Direct imaging of ionic clusters in a polyelectrolyte membrane by electron tomography.   J Am Chem Soc. 133, 20700-3 (2011)

L. R. Comolli, R. Duarte, D. Baum, B. Luef, K. H. Downing, D. M. Larson, R. Csencsits and J. F. Banfield.   A portable cryo-plunger for on-site intact cryogenic microscopy sample preparation in natural environments.   Microsc Res Tech. (2011)  doi: 10.1002/jemt.22001.

Y.-C. Yeh, L. R. Comolli, K. H. Downing, L. Shapiro and H. H. McAdams.  The Caulobacter Tol-Pal complex is essential for outer membrane integrity and the positioning of a polar localization factor   J. Bacteriol.  192, 4847–4858 (2010)

F. Amat, L. R. Comolli, J. F. Nomellini, F. Moussavi, K. H. Downing, J. Smit and M. Horowitz.   Analysis of the intact surface layer of Caulobacter crescentus by cryo-electron tomography.   J. Bacteriol.  192, 5855–5865 (2010)

Awards and Memberships

Fellow, Microscopy Society of America

Education

Ph.D., Cornell University, Applied Physics

Swiss Federal Institute of Technology (ETH), Institute for Cell Biology, Zurich, Switzerland



last updated: 2017-08-04 10:31:33