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DORIT HANEIN, PH.D.
Associate Professor
Infectious Diseases Program
858.646.3134 (phone)
858.646.3172 (fax)
dorit@burnham.org
Hybrid Methods 2008 Conference
RESEARCH FOCUS, BIOGRAPHY, PUBLICATIONS
Research Focus
My group studies molecular machines involved in the assembly and regulation of the actin cytoskeleton at the leading edge of motile cells. Structural characterization of these multimolecular protein complexes is likely to reveal potential mechanisms underlying cell growth, differentiation and migration as well as the role of these interactions in tumor invasion, metastasis and bacterial invasion. In particular, we study the role of Arp2/3 complex in actin filament network assembly, the role of myosin in cell migration, and the role of actin binding proteins in providing a scaffold for cell protrusions and adhesion.
We combine various electron cryomicroscopy, image analysis and bioinformatics techniques to extract high-resolution structural information of these large dynamic assemblies in their fully hydrated state. Electron cryomicroscopy is the principal method for solving the structures of large complexes that remain beyond the reach of NMR and x-ray crystallography. The high-resolution electron microscopy field is in a state of rapid development both on the instrumentation and computational fronts, utilizing a variety of new technology breakthroughs and image analysis approaches for producing 3D reconstructions of key macromolecular complexes.
Although high-resolution structural approaches provide critical information about individual molecules and complexes, a barrier to progress remains their structural and functional integration at the cellular level. Towards this end we are currently developing techniques and protocols that allows us to image whole cell, in their fully hydrate state, and to use bioinformatics tools, to correlate between the high-resolution structural information motives with the in situ characterization obtained from living cells.
Biography
Dorit Hanein earned her Ph.D. in Chemistry from the Weizmann Institute in Science, Rehovot, Israel in 1995. She received postdoctoral training at Boston University Medical School and Brandeis University, prior to her appointment as Assistant Professor at Burnham Institute for Medical Research in 1999. In 2000, Dr. Hanein was selected as a PEW Scholar in the Biomedical Sciences. In 2005, Dr. Hanein was promoted to an Associate Professor at the Burnham Institute and in 2006 has been also appointed an adjunct professor at the University of California, San Diego.
Selected Publications
Rouiller I, Xu XP, Amann KJ, Egile C, Nickell S, Nicastro D, Li R, Pollard TD, Volkmann N, Hanein D.
The structural basis of actin filament branching by the Arp2/3 complex. J Cell Biol. 180(5): 887-95, 2008.
Volkmann N, Liu H, Hazelwood L, Trybus KM, Lowey S, Hanein D. The R403Q Myosin Mutation Implicated in Familial Hypertrophic Cardiomyopathy Causes Disorder at the Actomyosin Interface. PLoS ONE. 2(11):el 123, 2007.
Faustin B, Lartigue L, Bruey JM, Luciano F, Sergienko E, Bailly-Maitre B, Volkmann N, Hanein D, Rouiller I, Reed JC. Reconstituted NALP1 inflammasome reveals two-step mechanism of caspase-1 activation. Mol Cell. 25(5): 713-24, 2007.
Janssen ME, Kim E, Liu H, Fujimoto LM, Bobkov A, Volkmann N, Hanein D. Three-dimensional structure of vinculin bound to actin filaments. Mol Cell. 21(2): 271-81, 2006.
Volkmann N, Liu H, Hazelwood L, Krementsova EB, Lowey S, Trybus KM, Hanein D. The structural basis of myosin V processive movement as revealed by electron cryomicroscopy. Mol Cell. 19(5): 595-605, 2005.
List of Publications via PubMed
(NIH National Library of Medicine)
