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Eva Nogales

structural biologist and biophysicist: Biosciences

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

 

Eva's lab is dedicated to gaining mechanistic insight into crucial molecular processes in the life of the eukaryotic cell.  Her primary research areas are, on one hand, the dynamic self-assembly of the cytoskeleton during its essential functions in cell division, and on the other, the molecular machines involved in macromolecular synthesis and degradation within the central dogma.

The unifying principle in her work is the emphasis on studying macromolecular assemblies as whole units of molecular function by direct visualization of their architecture, functional states and regulatory interactions. With this overall aim in mind, Eva's lab uses electron microscopy and image analysis, complemented with biochemical and biophysical assays, towards a molecular understanding of their systems of interest.

Recent research

Microtubule Dynamics and Interactions with Kinetochore Complexes

A long-standing interest of Eva's lab concerns the process of microtubule dynamic instability. She and her team have characterized tubulin polymers that they propose mimic the structural intermediates in the processes of microtubule assembly and disassembly. Eva is particularly interested in the role of nucleotide state in microtubule polymerization and structure.

Microtubule dynamic instability is essential during mitosis, and a number of cellular factors, included structural kinetochore components, interact with the dynamic ends of microtubules and are able to modify the behavior of these polymers. Most importantly, outer kinetochore complexes appear to make use of the unique structures at microtubule ends to harvest the energy of the nucleotide-coupled assembly and disassembly processes to carry out cellular work.  Eva's lab is defining the structure and regulated interaction of aouter kinetochores complexes with microtubules, including member of the KMN kinetochore network, the Ska complex and the yeast Dam1 complex.

Septins Assembly and Membrane Interactions

Septins are highly conserved GTPases that form filaments in vivo and in vitro and are essential in a variety of membrane remodeling processes, most notably cytokinesis. Eva is particularly interested in the combinatorial character of septin-septin interactions and the interplay between membrane interaction and septin self-assembly. Her lab has shown how the four essential mitotic yeast septins (cdc3, cdc10, cdc11 and cdc12) and the non-essential Shs1 come together in functional complexes and how they interact within filaments. They have described a marked enhancement in assembly that is totally dependent on and specific to PIP2, a signaling lipid known to be localized at the bud neck and to be essential to the cytokinetic process. Our recent characterization of the bud neck ultrastructure has shown the presence of coexisting septin filaments running both parallel and perpendicular to the bud axis. The relationship between in vivo phenotypes and septin assembly, organization, and interaction with different proteins, is a major interest in her lab.

Molecular Machines of the Central Dogma

During the last five years Eva has teamed her lab up with a number of collaborators in the study of molecular machines dedicated to nucleic acid information flow, with special emphasis on the mechanism of gene regulation. They defined the overall architecture of a number of complexes involved in the critical initiation steps of DNA replication, RNA transcription and translation, for which very little crystallographic information yet exist (e.g. ORC, TFIID, eIF3). They have also placed the crystal structures of essential elements in RNA processing and degradation in the context of fully functional complexes (e.g. exosome, RLC). A unique contribution of Eva's Lab EM studies in these projects, going beyond architecture and the bringing together of functional motifs, has been, and will continue to be, the capacity to detect conformational flexibility in large complexes and to place it in a functional context (e.g. TFIID regulation/promoter binding, functional elements in the RLC). They aim to gain mechanistic insight by describing conformational landscapes and their relationship to interactions with ligands and regulatory factors, and to use this information to formulate testable models of regulated, complex function.

Recent Publications

Wu, Z., Nogales, E. and Xing, J. (2012) Comparative Studies of Microtubule Mechanics with Two Competing Models Suggest Functional Roles of Alternative Tubulin Lateral Interactions. Biophys. J., in press

Querol-Audí J., Yan, C., Xu, X., Tsutakawa, S.E., Tsai, M-S., Tainer, J.A., Cooper, P.K., Nogales, E., Ivanov, I. (2012) Repair complexes of FEN1, DNA and Rad9-Hus1-Rad1 are distinguished from their PCNA counterparts by functionally important stability. PNAS, 109(22) 8528-33

Hudak JE, Barfield RM, de Hart GW, Grob P, Nogales E, Bertozzi CR, Rabuka D. (2012) Synthesis of Heterobifunctional Protein Fusions Using Copper-Free Click Chemistry and the Aldehyde Tag. Angew Chem Int Ed Engl., 51(17), 4161-5.

Patel, K., Nogales, E. and Heald R (2012) Multiple domains of human CLASP contribute to microtubule dynamics and organization in vitro and in Xenopus egg extracts Cytoskeleton , 69, 155-165

Lander, G.C., Estrin, E., Matyskiela, M.E., Bashore, C., Nogales, E. and Martin, A. (2012) Complete subunit architecture of the proteosome regulatory particle. Nature, 482 186-91

Bonacci W, Teng PK, Afonso B, Niederholtmeyer H, Grob P, Silver PA, Savage DF (2012) Modularity of a carbon-fixing protein organelle. Proc Natl Acad Sci, 109(2) 478-83

Bertin, A., MacMurray, M., Pierson, J., Thai, L., MacDonald, K., Zerh, E., Peters, P., Garcia III, G., Thorner, J. and Nogales, E. (2012) Three-dimensional ultrastructure of the septin filament network in Saccharomyces cerevisiae. MBoC , 23 423-432

Grob, P., Zhang, T.T., Hannah, R., Yang, H., Hefferin, M.L., Tomkinson, A.E. and Nogales, E. (2012) Electron microscopy visualization of DNA-protein complexes formed by Ku and DNA ligase IV. DNA Repair , 11, 74-81

Awards and Memberships

2007-2008      Fundación BBVA Chair in Biomedicine, Spain.
2005               Early Career Award by the American Society for Cell Biology
2005               Chabot Science Award for Excellence
2000               Burton Award by the Microscopy Society of America
1998               Outstanding Performance Award by LBNL
1989-1992      Bursary from the MRC (U.K.)
1989-1992      Doctoral fellowship by the Spanish Ministry of Education.
1984-1988      Undergraduate fellowship by the Spanish Ministry of Education

Education

PhD, Biophysics, University of Keele (UK)

BS, Physics, Universidad Autonoma de Madrid (Spain)

Videos


What It Means to Be an HHMI Investigator - Eva Nogales talks about her approach to science and why it's good to be fearless.

Eva Nogales, HHMI Investigator, University of California, Berkeley from Jim Keeley on Vimeo.



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