Biochemistry, Cell Biology
University of California, Los Angeles
Biologist Tracy Johnson delights in the details of science. As a student, she was captivated by the elegance of organic chemistry – she loved following the movement of electrons during chemical reactions and visualizing how molecules came together. The logic and exactitude of those interactions was compelling. “There are times in my education that it just hit me that something was really beautiful – that there was an elegance that was inspiring,” she says. “That's what makes science worth doing.”
Johnson wants her students to have that same experience. Each year, students at the University of California, Los Angeles have opportunities to find those moments in her molecular biology course, where she uses innovative, active teaching techniques and engages every student in an inquiry-based experience. And she has mentored dozens of undergraduate and high school students through research in her own lab, where she investigates how one of the cell's most complex molecular machines, the spliceosome, finds and removes sequences that interrupt genes.
The splicing process piqued Johnson's interest when she first learned about it in a high school biology class. In all but the simplest cells, sequences called introns interrupt the coding regions of genes. These non-coding bits are snipped out of the RNA copy of a gene, leaving a concise genetic code ready to be translated into protein. At the time, there were so many questions about how and why the process occurred, Johnson recalls.
As a graduate student in the University of California, Berkeley, biochemistry and molecular biology program, Johnson studied RNA transcription – how an RNA copy of a gene is produced. Many people were studying how cells controlled gene activity by slowing or accelerating the initiation of transcription, but Johnson looked at a later step: how additional building blocks were added to a nascent RNA molecule once transcription had begun.
Meanwhile, other labs were uncovering evidence that RNA molecules were spliced while they were still being transcribed from their DNA templates. “That meant that all the things we were learning about transcription were probably being overlaid on things that were happening during splicing,” she says. During postdoctoral research in John Abelson's lab at the California Institute of Technology, Johnson investigated the detailed biochemistry of splice-site recognition. “But in the back of my mind,” she says, “I was always interested in this intriguing likelihood that all of things we were studying were likely happening at the same time as transcription.”
Johnson has been delving into that relationship since she started her own lab at the University of California, San Diego, in 2003. Her genetic and biochemical studies in yeast have uncovered coordination between splicing (and other forms of RNA processing) and transcription. She has identified specific splicing proteins that influence how DNA is packaged, and thus how accessible genes are to the cell's transcriptional machinery. Her lab has also shown that modifications of the proteins that package DNA can influence the spliceosome's ability to recognize its target sequences. Now, Johnson's team at UCLA, where she moved in 2013, is building on what they've learned and is exploring how crosstalk between transcription and RNA processing lets cells regulate gene activity in response to environmental cues.
Johnson says she was supported early in her research career by mentors who gave her freedom and assumed she had important contributions to make. She wants her students to experience the same opportunities to succeed. She is concerned about poor retention rates for students in the sciences: “Nationally, less than 50 percent of students who say they want to be STEM majors graduate with STEM degrees. For students coming from underrepresented groups, the decline is even more dramatic,” she says. “It's rare to meet a child in elementary school who doesn't love science. So what happens?”
For one thing, she says, many students opt out before they ever encounter authentic research. “We wait too long to expose students to the discovery process,” she says. “Students need to feel that they are able to make an intellectual contribution to the scientific enterprise.”
Johnson equips her students to make those contributions by teaching them to think critically. Critical thinking can be practiced, she says, and she regularly asks students in her courses to think through how to frame questions and use available tools to answer them. “Even if students don't become research scientists, that's something that they need to take with them,” she says. But ideally, she says, students should experience the sense of discovery firsthand during their freshman year.
As an HHMI professor, Johnson is creating a Pathways to Success program that will give students a sense of scientific ownership early on. Students will gain confidence in using the tools of science as they help identify molecules that play a role in RNA splicing. Students who participate will become part of a learning community and receive mentoring from their peers, more advanced students, and faculty. Johnson will actively recruit students from local high schools to ensure a diverse cohort of participants. The hope, she says, is that the experience will give students the motivation to “work through the hard stuff,” complete undergraduate degrees in the sciences, and perhaps go on to advanced degrees. “We want to change the statistics for not only how many, but also who succeeds,” she says.