Thomas Walz, Ph.D.

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 explore these processes, 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 vesicular transport. Most recently, they have been exploring how a multisubunit complex known as the BBSome enables signaling receptors to cross the transition zone, the diffusion barrier at the base of sensory organelles called primary cilia.

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.