Kristian Baker becomes first School of Medicine NSF CAREER Award recipient

Kristian BakerThe National Science Foundation has bestowed its prestigious CAREER Award upon another outstanding Case Western Reserve University faculty member and, for the first time, to a researcher in the School of Medicine.

The highly competitive NSF CAREER Award was given to junior faculty member Kristian Baker, an assistant professor in the Center for RNA Molecular Biology, for her outstanding research and personal dedication to educating and training young scientists.

The CAREER Award, designed to support the integration of learning and scholarship, provides Baker with $1.3 million over five years to help fund her research on a vital cellular process called nonsense-mediated mRNA decay (NMD). This is one of the largest NSF grants ever awarded to any Case Western Reserve faculty member, and Baker is grateful to have support for her research in a way that also reinforces positive mentorship and development of her students.

The Baker lab is housed in the Center for RNA Molecular Biology, headed by Director Timothy W. Nilsen. As the first research unit of its kind to concentrate scientists focused on understanding the metabolism and function of RNA, the center remains one of the premier RNA research facilities in the country. Within her lab, Baker provides unique research opportunities to students from local high schools as well as undergraduate and graduate students.

The CAREER Award’s primary focus is on Baker’s research into NMD, an important quality control mechanism through which cells are able to recognize and remove damaged mRNA to prevent the production of non-functioning proteins.

In order to construct a protein, DNA of the corresponding gene is first transcribed into messenger RNA (mRNA). This works the same way as a copy machine that creates a duplicate while preserving the integrity of the original.

The mRNA, as the information carrier, holds the instructions to build a protein. But if a mistake is made during transcription, or if the original DNA acquires a mutation, the result is a flawed duplicate that cannot serve its purpose. “Mistakes happen all the time in biology,” Baker said. “Nothing is perfect, but when a mistake happens, the cell can either ignore it and suffer the consequences, or recognize and deal with it.”

This is where her research comes in. NMD is carried out by a complex molecular machine that assesses whether or not the mRNA is flawed, in much the same way that industrial quality control mechanisms prevent factories from distributing defective merchandise. Normal mRNA are ignored by the NMD machinery and proceed to build the correct protein, while flawed mRNA are targeted by the NMD quality-control mechanism for elimination.

If left unchecked, these flawed mRNA would produce non-functional proteins or, worse yet, proteins that could wreak havoc on otherwise healthy cells.

While scientists like Baker have known that NMD exists and plays an important role in cells, no one is certain how the process works.

This is what Baker proposes to discover under the research component of her CAREER award. She hopes to reveal characteristics of mRNA which are recognized and targeted by NMD to fully understand how the quality-control mechanism functions. The research will use yeast—a less complex organism whose NMD process mirrors that of human cells—as the primary vehicle for testing.

She and her team will be using new, innovative technologies including next-generation sequencing to profile and characterize mRNAs targeted by NMD. As opposed to the traditional method of looking at mRNAs one by one, this new comprehensive approach will allow all the mRNAs in a cell to be simultaneously evaluated.

While Baker’s selection as a CAREER Award recipient centered on her proposed research, her commitment to teaching and training was also an important consideration. With the funding, Baker will expand her research objectives as well as develop new, exciting possibilities for student development. One of those is the creation of a new third-year undergraduate seminar course focusing on the challenges faced by women and minorities pursuing careers in science and the resources available to help those students succeed.

Baker is quick to acknowledge the importance of mentors in her own life and career, expressing her desire to support her own students in the same way. “I want to give them every opportunity to be successful and develop as well-rounded scientists. And at the end of the day,” she added, “they’re engaged in the work and care about the outcome, so the investment ultimately benefits both the student and the goals of the research.”

Baker’s intention under the CAREER Award is to understand NMD as a basic biological process, but her findings may lay a foundation for future research in advancing human health. One-third of all genetic diseases are caused by the kinds of flaws in mRNA that are targeted by the NMD machinery.

“You can’t fix a car if you don’t know how a car works,” Baker explained. “So if we can understand how the NMD process functions at a fundamental, molecular level, then, in the future, scientists might be able to use this information to develop targeted therapies that can treat symptoms associated with a wide range of genetic diseases.”

Jo Ann Wise, a professor in the RNA Center and faculty mentor to Baker, is excited to participate in the proposed undergraduate seminar course. She knows that Baker’s research program exemplifies the objectives of a CAREER Award. “The main reason that Kristian succeeded, when the competition is so strong, is absolutely based on the stellar quality of her basic research and her constant commitment to integrating it with education and training.”