Research Expertise and Interest

cryo-EM, biochemistry, complex biological assemblies, structure and regulation of the cytoskeleton, microtubule dynamics, human transcriptional initiation machinery, epigenetics, gene silencing, biophysics

Research Description

Eva Nogales is a Professor of Biochemistry, Biophysics and Structural Biology, and a Howard Hughes Investigator.  The Nogales lab is dedicated to gaining mechanistic insight into crucial molecular processes in the life of the eukaryotic cell. Their two main research themes are the dynamic self-assembly of cytoskeleton during its essential functions in cell division, and the molecular machines governing the regulation of gene expression, specially at the transcriptional level. The unifying principle in their 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 they use electron microscopy and image analysis, complemented with biochemical and biophysical assays, towards a molecular understanding of their systems of interest.

Current Projects

Microtubule Structure and Dynamics
Microtubules are essential cytoskeletal polymers involved in processes as diverse as intracellular traffic and cell division. A long-standing interest of her lab concerns the process of microtubule dynamic instability and its role in mitosis. A large number of cellular factors regulate this dynamic behavior. We have defined the structure of the microtubule at the atomic level, and the conformational changes that accompany GTP hydrolysis and lead to microtubule destabilization, Their microtubule cytoskeleton studies also emphasize the dynamic interactions of microtubule  with cellular factors, specially those involved in cell division. Many such factors, by interacting with the dynamic ends of microtubules, are able to modify the behavior of these polymers and to make use of the unique structures at microtubule ends to localize in space and time, or to change microtubule dynamics.

Regulation of Gene Expression: Transcription Initiation
The regulated transcription of genes in all eukaryotes requires the assembly of a complex molecular machine around the transcription start site. Electron microscopy is ideally suited to the study large macromolecular complexes. The Nogales lab has used cryo-EM to define the structure and functional transitions of the human transcription preinitiation complex, which includes TFIID, TFIIA, TFIIB, TFIIE, TFIIF, TFIIH and RNA pol II. Their goal is now to characterize their mechanism of action in the context of chromatin, as well as their interaction activators, repressors and cofactors to generate an integrated, mechanistic model of transcriptional regulation.

Regulation of Gene Expression: Gene Silencing by PRC2

Polycomb Repressive Complex 2 (PRC2) is essential for gene silencing, establishing transcriptional repression of specific genes by tri-methylating Lysine 27 of histone H3, which ultimately lead to chromatin compaction. The NOgales lab have used cryo-EM to define the structure of PRC2 bound to two critical cofactors, and visualized the interaction of PRC2 bound to a dinucleosome. We are continuing our structural studies, complemented with activity assays, to explore the complex regulation that arises form the cross-talk between PRC2 dofferent cofactors and different chromatin state (post-translational modifications of histone tails).

In the News

AAAS Adds Ten New Fellows From UC Berkeley

Ten members of the UC Berkeley community – including nine faculty and one staff member — have been elected American Association for the Advancement of Science (AAAS) fellows, one of the most distinctive honors within the scientific community.

Five Berkeley scientists named to National Academy

The National Academy of Sciences, the nation’s oldest and most prestigious scientific organization, has elected five UC Berkeley faculty members to its ranks, raising the number of members on campus to 143.

New insight into an emerging genome-editing tool

Biochemist Jennifer Doudna and biophysicist Eva Nogales led an international collaboration with results that point the way to the rational design of new and improved versions of Cas9 enzymes for basic research and genetic engineering.

New Key to Organism Complexity Identified

The enormously diverse complexity seen amongst individual species within the animal kingdom evolved from a surprisingly small gene pool. The key to morphological and behavioral complexity, a growing body of scientific evidence suggests, is the regulation of gene expression by a family of DNA-binding proteins called “transcription factors.”

Focusing on a key event in life of a chromosome

If chromosomes are to separate properly during cell division, the microtubules in the cell must grab onto them and pull them apart. The place where the microtubules latch on is a large molecular complex called the kinetochore. Eva Nogales and her UC Berkeley/LBNL team have created the first high-resolution image of this junction and identified regulators that prevent errors that can lead to cancer or death.

Featured in the Media

Please note: The views and opinions expressed in these articles are those of the authors and do not necessarily reflect the official policy or positions of UC Berkeley.
November 29, 2018
In a significant advance in cryo-electron microscopy and progress in understanding how the body converts DNA into RNA, a team of Berkeley scientists led by molecular and cell biology professor Eva Nogales has captured freeze-frames of a critical molecular process. The research is expected to help drug developers design drugs that interfere with the process to alter the expression of genes causing disease. This story originated at Berkeley News.
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