Penn’s Brian Gregory Is ‘Making Major Strides’ in RNA Biology

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Media Contact:Katherine Unger Baillie | | 215-898-9194February 15, 2013

Everyone has heard of DNA, the blueprint for life. But if it were up to Brian Gregory, an assistant professor of biology at the University of Pennsylvania, DNA’s close cousin, RNA, would get equal billing.

Gregory studies RNA, or ribonucleic acid, primarily in plants in his lab at Penn, investigating not only how it functions as a code for building proteins but also how it serves to regulate gene expression.

This exploration of the crossroads where plant biology and RNA biology meet has been a fruitful one for Gregory. Using high-throughput sequencing technology and computational-biological techniques, he has been tallying and publishing discoveries at a furious rate since arriving at Penn in 2009.

“Brian is making major strides at the intersection of RNA biology, plant biology and genomics,” says Greg Guild, chair of Penn’s Department of Biology.

A Faculty Early Career Development award from the National Science Foundation, known as a CAREER award, is supporting this work, as well as Gregory’s efforts to train the next generation of biologists to keep up the healthy pace he has set.

Though until recently, RNA hasn’t attracted the limelight, that trend is changing. More and more, RNA molecules are seen playing important roles in determining how and whether genes synthesize a product.

In a study published in November in the journal The Plant Cell, Gregory and his Penn colleagues document how the interactions of RNA nucleotides, known as the secondary structure of RNA, influences its regulation and function.

He found that highly structured RNA molecules in the plant model organism Arabidopsis thaliana tend to be targeted for degradation.

“It seems that if a [messenger RNA] folds into certain types of structures, it gets processed into small RNAs,” Gregory says. “That’s why levels of mRNAs go down as their structure increases.”

Among other possibilities, Gregory suggests that this attribute of structure in RNAs may have evolved as a way for plants to distinguish between their own genetic material and foreign material, as a way of destroying viruses or other pathogens that may try to attack plants.

“It seems that these highly structured mRNAs are being processed because they look kind of like pathogens,” Gregory says.

Understanding how RNA behaves in plants could allow researchers to manipulate that behavior, laying the groundwork for practical applications.

“Gene expression regulation is something we think about from the perspective of crop improvement,” says Gregory. “If we can develop new tools for regulating specific genes in plants that improve yield and that improve biomass, that will help breed plants that are more successful and useful to humans.”

Interestingly, in animals, preliminary studies of a nematode and a fruit fly show the opposite trend: In these species, more structured RNA molecules are not destroyed. Gregory hopes to look in still more species to see how these mechanisms may have evolved through different evolutionary branches.

This move beyond plants could even hold potential implications for human health and disease. A growing number of diseases, notably some neurodegenerative disorders, are associated with defects in RNA.

“We know that some RNA molecules are incredible regulators and that can teach us about what goes awry in some human diseases,” says Gregory.

With so much on his plate, it would be difficult for Gregory to accomplish all he wants to on his own. Fortunately, he got into the field as much to be an educator as a researcher.

“In addition to postdocs and grad students, Brian has trained an army of undergrads in his lab who seem to be a key component to his success,” Guild says. “He is basically trying to bring genomic biology to every undergraduate and graduate student he contacts.” 

Involving students in his work has been mutually beneficial. As students in Gregory’s lab gain expertise in the fields such as RNA and computational biology, they’ve become significant contributors and even coauthors on published studies. And the training they receive serves them well in the next steps in their career.

“I have two trainees who are now M.D./Ph.D. students at Columbia Medical School and one who is a M.D. student at Penn,” says Gregory. “Just seeing them go out and carry on that training, you feel a kind of glee that you had some hand in that.”

Beyond working with students in his lab, Gregory has developed two new courses at Penn that help him further prepare the next generation of biologists. One course focuses on genomic science and medicine, while the other immerses students in RNA biology.

With the CAREER award support, Gregory will have students in these courses analyzing the actual data from his studies to get even more intimately familiar with the computational techniques that are becoming increasingly omnipresent in biological research. He plans to begin to implement some of these hands-on analyses in the next iteration of his genomics course, in the spring of 2014.

“This is what I feel is the next frontier in our field,” says Gregory. “If you look up and down the hall in our department, everybody’s papers coming out now involve computationally based analysis. So I want to make sure the students are well prepared.”