Professor Elizabeth Wright, director of the cryo-EM facility at UW–Madison
Cryo-EM Expert Elizabeth Wright Joining Biochemistry to Direct New Facility

The University of Wisconsin–Madison Department of Biochemistry will welcome Elizabeth Wright in July as a faculty member and director of the department’s newly established cryo-electron microscopy (cryo-EM) facility.

Wright is an expert in cryo-EM, a technique able to obtain atomic or near-atomic level resolution images of biological molecules by imaging with electrons. It is a burgeoning technology that can help UW–Madison researchers make significant new contributions to many areas of structural biology, including enzymology, virology, cell biology, and medicine.

“I am very excited to be joining the department to develop this technology at UW–Madison,” says Wright, who will also be an affiliate of the Morgridge Institute for Research. “In the fields of fundamental biochemistry and structural biology, the department is one of the strongest in the country. I was drawn to UW–Madison by the vision the department has for this facility. We are not just thinking about the present but about the next decade and beyond by establishing an advanced cryo-EM resource and building a community to push forward scientific understanding across many biological research areas by using cryo-EM.”

Wright did her undergraduate education in biology and chemistry at Columbus State University and her Ph.D. in chemistry at Emory University. Following postdoctoral work at the University of Southern California and CalTech, she was an associate professor in the Department of Pediatrics in the Emory University School of Medicine and was the director of the Robert P. Apkarian Integrated Electron Microscopy Core at Emory University before joining UW–Madison.

“We are pleased to welcome Liz to lead our upcoming state-of-the-art cryo-EM facility,” says biochemistry professor and chair Brian Fox. “Her extensive expertise and experience in this technique and dedication to building a community contribute to the high level of excitement that is building around this initiative.”

Wright’s research interests are varied but all revolve around advancing and utilizing sophisticated light and electron microscopy imaging technologies. In technology development she works to push the limits of cryo-EM with phase plates, direct electron detectors, and automation. She also develops tools and methods that help bridge the gap between cryo-EM and other types of imaging and structural biology technologies, such as light microscopy, protein crystallography, and nuclear magnetic resonance (NMR), that the department and campus already utilize. Correlation of these different methods provides a powerful future opportunity to guide and expand research on campus.

On the biological side, she studies bacteria and how cells regulate interactions with the environment through their appendages, such as pili and flagella. Pili are thin filaments that extend and retract from bacterial cells. Pili provide motility, but also allow bacteria to adhere to substrates, colonize them, and form larger communities. By understanding the structure of bacterial pili, she will be able to consider how their function can be altered. Flagella are used for motility and Wright and her research group want to determine why some cells have flagella comprised of a single flagellin protein while others have multiple copies of different flagellins. Wright plans to answer a number of questions, including, does retaining multiple flagellins confer some level of fitness to the organism? Are the flagellins incorporated uniformly along the length of the flagellum?

Cryo-EM image of reovirus T1L particles. They are displaying  attachment fibers as indicated by white arrowheads.
Cryo-EM image of reovirus T1L particles. They are displaying attachment fibers
as indicated by white arrowheads. These viruses causes respiratory and
intestinal inflammation. Image courtesy of Rebecca S. Dillard of Emory University
and Elizabeth R. Wright of UW–Madison.

She also studies the structures of enveloped viruses like HIV, measles virus, respiratory syncytial virus, and the flu virus. Her group is resolving the structures of viruses and viral proteins during the processes of virus entry, replication, assembly, and maturation. Learning about these structures and processes is important for basic biological understanding but could also come in handy for finding ways to fight the viruses, she says.

An area she is beginning to explore is neurodegenerative disease, such as Alzheimer’s and Parkinson’s, that are caused by defective proteins. Understanding at the molecular level how these proteins impact neuronal cell structure and function may support the development of new therapeutic and curative approaches.

“Broadly speaking, we are interested in how biological systems work, for example, how all the components of a cell carry out individual functions that combine to maintain a healthy cell,” Wright explains. “While much of our work focuses on fundamental biology, we also consider the translational aspects of our research. In order to help develop new therapeutics, antimicrobials, and antivirals we need to understand these basic structures at various levels of resolution. This helps us know if our potential drug could actually disable a virus or bacterium, for example, or if the organism would have a way to counteract our drug.”

Besides her own research, Wright will build a community of researchers on campus that utilize cryo-EM in their work. The upcoming facility is a cross-campus effort led by the Department of Biochemistry but will be useable by all of campus and beyond. Along with the department, funding for the facility has come from the Morgridge Institute, Office of the Vice Chancellor for Research and Graduate Education, College of Agricultural and Life Sciences, School of Medicine and Public Health, UW Carbone Cancer Center, and departments of Biomolecular Chemistry and Neuroscience. For more information on the upcoming facility and how the technology works, see the Department of Biochemistry website.

“This facility will bridge across the campus’s structural biology community, from light microscopy to NMR to x-ray crystallography,” Wright says. “I can see it spanning from basic biology, medicine, and agriculture to engineering and computer science. Along with the Titan Krios 300 kV cryo-TEM, the centerpiece of the new facility, we will acquire three other microscopes. The suite of instruments will allow us to interrogate complex biological systems and their structures in new ways, to gather as much data as possible, and support correlative studies with other structural biology techniques.”

Wright’s interest in imaging and cryo-EM stems from her artistic background. While she decided to make her love of science into her career, she is still very visually oriented and enjoys painting, particularly landscapes. She says imaging technologies like cryo-EM help her retain her artistic eye. She adds that microscopy also lends itself well to science outreach, particularly with children, and she wants to continue working in that area at UW–Madison.

Cryo-EM also offers a chance to advance the education of students in the department and across campus. Wright plans to teach both junior-level and advanced courses on the technology and its uses after spending time setting up the facility.

“Education is very important to me,” she says. “In the broader scale, cryo-EM is really going to enable us to think differently about viruses, bacteria, and cells and how they function. Those cartoon drawings and conventional election microscopy images in textbooks are not completely accurate and this technology will allow us to rewrite virology, bacteriology, and cell biology books. It will enhance our capability to understand these systems now but also to give that information to the next generations of scientists we’re training here at UW–Madison.”