Dr. Walz is interested in processes that involve biological membranes, ranging from vesicular transport that distributes cargo molecules throughout the cell to how lipids affect the structure and function of membrane proteins. To address these questions, he applies a variety of techniques in electron microscopy to visualize macromolecular complexes and membrane proteins, aiming to determine structures at the atomic level.
Biological membranes surround cells and cellular compartments and thus have to relay signals and allow cargo transport. They also catalyze reactions and mediate all interactions cells have with their environment and other cells. These functions are carried out by proteins embedded in the membranes, and an increasing number of 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 a membrane protein’s native environment. Meanwhile, cellular membranes contain thousands of different lipids, and it is being increasingly recognized that this diversity affects most membrane processes as well as many aspects of the embedded membrane proteins.
Dr. 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 thus the function of membrane proteins. To accomplish this, he uses a variety of electron microscopy techniques and new biochemical approaches that make 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 allow images of unprecedented quality to be recorded. Together with new image processing algorithms, DDD cameras have opened up new avenues for structural investigations. The Walz lab aims to exploit these new developments to study the structure and dynamics of proteins within the membrane, and to visualize the effects lipids and other membrane characteristics exert on these proteins.
DDD cameras make it possible to obtain high-resolution images of tubular crystals, helical arrangements of membrane proteins in lipid bilayers that can be used for structure determination. The Walz lab is now working on tubular crystals for a number of transporter proteins in order to examine their structure in different functional states to elucidate their transport cycle.
Nanodiscs are small patches of lipid bilayer stabilized by a scaffold protein that recreate a membrane protein’s native environment and associated characteristics, something not provided by detergents, which are traditionally used to prepare membrane proteins for electron microscopy. The Walz lab uses nanodiscs to visualize how specific lipids or membrane characteristics induce conformational changes in membrane proteins, asking, for example, whether or not 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, how multisubunit tethering complexes help to ensure that transport vesicles fuse with the appropriate target membrane.
Dr. Walz’s earlier work includes using 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.