Dorit Hanein's Research Focus
Dorit Hanein's Research Report
Electron cryo-microscopy (cryo-EM) has grown to be a powerful imaging technique applicable to almost any kind of specimen, is parsimonious in its material requirements, and allows imaging of large macromolecular assemblies close to their physiological environment. Cryo-EM provides the means to determine three-dimensional (3D) structures of pleiomorphic macromolecular assemblies in fully hydrated state, close to their native environment. Dr. Hanein’s laboratory is continuously developing and applying various cryo-EM, image analysis and bioinformatics approaches and techniques to extract high-resolution structural information of these large dynamic assemblies at the highest level of fidelity. Using a hybrid approach, Hanein and collaborators combine the generated 3D maps of the assemblies with high resolution information such as that derived from atomic resolution structures of their components, yeast two-hybrid screening, mutagenesis, biochemical and biophysical data to link structural correlates to functional outputs. The derived molecular models enable understanding of the mechanisms by which large and dynamic assemblies function and by which mutations or pathogens elicit non-regulated responses, providing benchmarks for the kinds of regulatory mechanisms associated with function in vivo.
One of the prime biological interests in Dr. Hanein’s laboratory is elucidating the molecular mechanisms underlying the assembly and regulation of the actin cytoskeleton and its associated integrin-mediated adhesions at the leading edge of motile cells. Dr. Hanein successfully applied the hybrid approaches described above to several biomedically relevant systems. Examples include studying the role of Arp2/3 complex in actin filament network assembly, the role of myosin in cell migration, the role of actin binding proteins in providing a scaffold for cell protrusions and adhesion (for example Vinculin, Talin, EPS8, Tensin, Fimbrin), and the connection of this machinery to the extracellular matrix (Integrins, Fibronectin). Other biological interests in the Hanein laboratory include pathogen invasion, the inflammatory pathway, and apoptosis.
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. Toward this end, the Hanein laboratory is currently developing techniques and protocols that allow imaging whole eukaryotic cell, in their fully hydrated state, and to use computational tools to correlate between the high-resolution structural information we obtained from the isolated molecules and assemblies with the in situ characterization obtained from living cells (correlative light and electron microscopy). All these projects are in close collaboration with biology, biochemistry and computational biology labs, some of them extremely long standing within the Sanford Burnham Prebys, in the US and in the world.
Dorit Hanein's Bio
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 Sanford-Burnham Medical Research Institute 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 Sanford-Burnham and in 2006 has been also appointed an adjunct professor at the University of California, San Diego.
Chair, Hybrid Methods 2008 Conference
Organizing Committee, Hybrid Methods 2010 Conference
2011: Sanford-Burnham Symposium: Structural Systems Biology
Hanein D, Horwitz AR
Curr Opin Cell Biol 2012 Feb ;24(1):134-40
Methods Enzymol 2010 ;483:203-14
Hertzog M, Milanesi F, Hazelwood L, Disanza A, Liu H, Perlade E, Malabarba MG, Pasqualato S, Maiolica A, Confalonieri S, Le Clainche C, Offenhauser N, Block J, Rottner K, Di Fiore PP, Carlier MF, Volkmann N, Hanein D, Scita G
PLoS Biol 2010 Jun 1 ;8(6):e1000387
Biophysical Characterization of a Nanodisc with and without BAX: An Integrative Study Using Molecular Dynamics Simulations and Cryo-EM.
López CA, Swift MF, Xu XP, Hanein D, Volkmann N, Gnanakaran S
Structure 2019 Jun 4 ;27(6):988-999.e4
Metlagel Z, Krey JF, Song J, Swift MF, Tivol WJ, Dumont RA, Thai J, Chang A, Seifikar H, Volkmann N, Hanein D, Barr-Gillespie PG, Auer M
J Struct Biol 2019 May 1 ;206(2):149-155
High Rac1 activity is functionally translated into cytosolic structures with unique nanoscale cytoskeletal architecture.
Marston DJ, Anderson KL, Swift MF, Rougie M, Page C, Hahn KM, Volkmann N, Hanein D
Proc Natl Acad Sci U S A 2019 Jan 22 ;116(4):1267-1272
Anderson KL, Swift MF, Hanein D, Volkmann N
Biophys Rev 2018 Dec ;10(6):1571-1575
Kumar A, Anderson KL, Swift MF, Hanein D, Volkmann N, Schwartz MA
Biophys J 2018 Oct 16 ;115(8):1569-1579
Conformational Equilibrium of Human Platelet Integrin Investigated by Three-Dimensional Electron Cryo-Microscopy.
Hanein D, Volkmann N
Subcell Biochem 2018 ;87:353-363