Elizabeth Ransey Examines, Rewrites Cellular Communication
By Ann Lyon Ritchie
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Biochemist Liz Ransey was presented with a challenge: design and engineer interactions between a pair of proteins thought to be key to treating psychiatric disorders.
Now an assistant professor in Carnegie Mellon University's Department of Biological Sciences, she plans to further research at her new lab.
The impetus came from a mentor at Duke University, where Ransey worked as a postdoctoral fellow. The hypothesis had been that if communication increased between two brain regions — a circuit — that are malfunctioning in a disease, it could be treated. The goal had been to reengineer existing proteins — connexins (Cxs) — that form gap junction channels, or pores between adjacent cells, to increase this communication.
"Gap junctions connect all the cells in our bodies to exchange information and resources," Ransey said. "They essentially synchronize cells so that they are coordinated and form tissues with common function and behavior.
"Think of the coordination of electricity throughout the cells in your heart or in your brain and synchronized contractions of the uterus during childbirth. These are a tiny, though clearly critical, subset of the roles of gap junctions throughout the body."
The major challenge centered around the fact that there are 21 versions — called isoforms — of these proteins in humans that are interacting with numerous partners, in ways that are not fully known Ransey said.
Ransey led a research team at Duke University to develop a first-of-its-kind Cx interaction assay, termed FETCH (Flow Enabled Tracking of Connexosomes in HEK cells), and to employ FETCH and computational modeling to reconfigure two Cx proteins to be very specific and exclusive partners. These engineered Cxs form the basis for the neuromodulatory tool termed LinCx (Long-Term Integration of Neural Circuits using Connexins) that was shown to increase communication between neurons and change behavior in multiple animal models: a major advance in the field of neuromodulation.
In her Carnegie Mellon lab, Ransey will continue studying gap junction structure and function, focusing on filling in the gaps of knowledge on their individual interactions and the functional consequences of their mixing. While there are 21 isoforms of these proteins, she said they can mix and match into more than 200 combinations.
"There are a lot of outstanding questions about what cells are communicating to each other through gap junctions," Ransey said. "Understanding these features of Cx proteins is of fundamental value and interest to understanding the biology of healthy and diseased states and relevant to virtually anything you could think of, such as cardiac arrhythmias, wound healing, organ transplants, infertility, cataracts, congenital deafness and more."
A Toledo, Ohio native, Ransey earned a bachelor's degree in biochemistry at the Rochester Institute of Technology, before entering Carnegie Mellon's Biological Sciences graduate program.
"When I came to CMU for the graduate program, I felt really encouraged by the faculty about using my unique background, skills and ways of thinking from multiple disciplines to approach a Ph.D. project," Ransey said. "The collegial environment and the interdisciplinary nature of the department is absolutely what drew me here, both as a student and now as faculty."
Ransey studied at Carnegie Mellon from 2010 to 2013, receiving a Graduate Research Fellowship from the National Science Foundation (NSF) and a research dissertation fellowship from the United Negro College Fund (UNCF) — Merck Science Initiative Graduate Research Fellowship.
She developed an interest in using X-ray crystallography to answer questions about protein-RNA interactions, before transitioning to Harvard University to complete her Ph.D., writing a dissertation "Mechanistic and Functional Studies of RNA Processing Pathway Components" under advisor Piotr Sliz in 2017. Since joining the faculty, she has made connections within the Carnegie Mellon community through her identity as a first-generation college student and a Black, female scientist.
"Representation, transparency and communication are incredibly valuable and important to fostering an inclusive and diverse community, and one that fully actualizes its creative potential," she said. "Diversity is incredibly important to research innovation. We need individuals from diverse backgrounds to bring their unique perspectives and skills to the scientific workforce to attempt resolving problems that have persisted, as well as to identify problems and disparities in their specific communities."
Ransey's lab opened on Jan. 1.
"Right now, we have a ton of exciting ideas and all of the means to pursue them," Ransey said. "I truly believe we are in the best place to achieve our goals, and I am thrilled to have this opportunity."