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Heads of Laboratories

Head shot of Thomas Walz
Thomas Walz, Ph.D.
Professor
Laboratory of Molecular Electron Microscopy
thomas.walz@rockefeller.edu

Walz is interested in processes that involve biological membranes, ranging from vesicular transport that distributes cargo molecules throughout the cell to the effects of lipids on the structure and function of membrane proteins. To address these questions, he applies cryo-electron microscopy to image macromolecular complexes and membrane proteins, aiming to visualize their dynamics and determine their structures at the atomic level.

Biological membranes surround cells and cellular compartments, and have to relay signals and allow cargo transport. They also catalyze reactions and mediate all interactions cells have with their environment and with other cells. These functions are performed by proteins embedded in the membranes, and increasingly, structures of these membrane proteins reveal how they can carry out their activities. However, most of this structural work is being conducted on isolated membrane proteins in solution, without the lipid bilayer that is the native environment of a membrane protein. Meanwhile, cellular membranes contain thousands of different lipids. It is increasingly being recognized that this diversity affects most membrane processes as well as many aspects of the embedded membrane proteins.

Walz is broadly interested in processes related to cellular membranes, and much of his current work focuses on exploring how lipids affect the structure and function of membrane proteins. He uses single-particle cryo-electron microscopy and nanodiscs, a biochemical tool that makes it possible to explore the structure and function of membrane proteins in the context of lipid bilayers.

An exceptionally exciting development in electron microscopy is the introduction of direct electron detector device (DDD) cameras that record images of unprecedented quality. Together with new image processing algorithms, DDD cameras have opened up new avenues for structural investigations. The Walz group aims to exploit these new developments to study the structure and dynamics of proteins within the membrane, and to visualize the effects that lipids and other membrane characteristics exert on these proteins.

Nanodiscs are small patches of lipid bilayer stabilized by a scaffold protein that recreate the native environment of a membrane protein and its associated characteristics—something that cannot be achieved by detergents, which are traditionally used to prepare membrane proteins for electron microscopy. The Walz group uses nanodiscs to visualize lipid-induced conformational changes in membrane proteins, asking, for example, whether the thinning of a membrane is sufficient to open certain channels.

The lab is also investigating other membrane-related processes, such as membrane repair and vesicular transport. For example, they are exploring how multisubunit tethering complexes help ensure that transport vesicles fuse with the appropriate target membrane.

Walz’s earlier work includes the use of electron crystallography to determine the structure of the archetypal water channel, aquaporin-1, and as an approach to study how membrane proteins interact with their annular lipids.

Walz is a faculty member in the David Rockefeller Graduate Program, the Tri-Institutional M.D.-Ph.D. Program, and the Tri-Institutional Ph.D. Program in Chemical Biology.


EDUCATION

Diploma in biophysics, 1992
Ph.D. in biophysics, 1996
Biozentrum, University of Basel

POSTDOC

University of Sheffield, 1996–1999 

POSITIONS

Assistant Professor, 1999–2004
Associate Professor, 2004–2006
Professor, 2007–2015
Harvard Medical School

Professor, 2015–
The Rockefeller University

Investigator, 2008–2015
Howard Hughes Medical Institute

AWARDS

Genzyme Award for Outstanding Achievement in Biomedical Sciences, 2004

SELECTED PUBLICATIONS

Chou, H.T. et al. CATCHR, HOPS and CORVET tethering complexes share a similar architecture. Nat. Struct. Mol. Biol. 23, 761–763 (2016).

Blok, N.B. et al. Unique double-ring structure of the peroxisomal Pex1/Pex6 ATPase complex revealed by cryo-electron microscopy. Proc. Natl. Acad. Sci. U.S.A. 112, e4017–e4025 (2015).

Cheng, Y. et al. A primer to single-particle cryo-electron microscopy. Cell 161, 438–449 (2015).

Tan, D. et al. The EM structure of the TRAPPIII complex leads to the identification of a requirement for COPII vesicles on the macroautophagy pathway. Proc. Natl. Acad. Sci. U.S.A. 110, 19432–19437 (2013).

Hite, R.K. et al. Principles of membrane protein interactions with annular lipids deduced from aquaporin-0 2D crystals. EMBO J. 29, 1652–1658 (2010).