Linda Columbus Investigates Cell Membranes With Large New Grants

January 29, 2010 — While cell membrane proteins are abundant, constituting about 25 percent of the typical cell genome, scientists understand the molecular architecture of only about 100 of these cell "gatekeepers," which selectively mediate the flow of information and nutrients across the walls of the cell from external environments.

Linda Columbus aims to know much more. Armed with nearly $1.7 million in new funding from the National Institutes of Health and the National Science Foundation, Columbus, an assistant professor of chemistry at the University of Virginia, is bridging the gaps in knowledge of how these membrane proteins work, and how they might be regulated to allow in certain drug chemicals, or to keep out invading antigens.

The work ultimately could improve the ability of researchers to develop new pharmaceuticals that would target the root causes, at the cellular level, of an array of infectious diseases, including gonorrhea and meningitis.

"Membrane proteins are responsible for several cell functions, such as neurotransmission and cell signaling, and are targeted by 60 percent of the drugs on the market," Columbus said. "But there still is a lot more to know about their functions and architectures."

Columbus is particularly focused on determining how bacteria interact with human cells. An understanding of these molecular interactions would provide insights for ways to design new antibiotics and vaccines.

One of her grants, for slightly more than $1 million from NIH, supports her investigation into the interactions between bacterial outer membrane proteins and the receptors of the host cells to which they attach. It is known that some bacterial membrane proteins are able to "hijack" human cellular pathways by mimicking or manipulating the inner machinery of host cells. Columbus' goal is to learn how this happens so as to aid the eventual design of targeted antibiotics.

Her other major grant is a $680,000 NSF Faculty Early Career Development award, designed for young faculty who are particularly adept at integrating research and education. The grant encourages promising "high-risk" research like Columbus'.

"Investigations of membrane proteins are considered 'high-risk' mainly because preparing protein samples is difficult to do," Columbus said. "The process is difficult, expensive and time-consuming, thereby limiting the progress of our knowledge. I am seeking to overcome several challenging hindrances by establishing innovative lab methods that could give a clearer picture of the structural stability of these proteins."

Another aspect of her NSF award is to encourage female and minority students, at the middle school level through college, to pursue learning or careers in chemistry. At U.Va., she has helped introduce a new undergraduate biochemistry curriculum that steps away from traditional textbook-oriented learning toward active inquiry and research-based learning. She regularly participates in one-on-one and group mentorship programs, including a lunch series with U.Va. students.

Columbus and other women science faculty members lead interactive outreach programs, such as the U.Va. Young Woman Leadership Program, which introduce middle school girls to science. The students tour chemistry laboratories, see science in action, and participate in hands-on activities – all hosted by female faculty, graduate students and postdoctoral fellows.

Columbus is quick to point out that part of her success is due to the dedicated work of the graduate students and lab specialists in her lab, as well as to the undergraduates who increasingly participate in active research under her mentoring.

"They work really hard and are a great team," she said.

— By Fariss Samarrai