mysterious, regulators of biological functions. “There’s been a lot of work to show that certain microRNAs are up-regulated or down-regulated in specific sub-types of cancer. So we have this correlation, but we don’t know their normal function,” explains Abbott. If the concept of biologically functional RNA is not new, what was novel was how Abbott and her team discovered biological roles for individual microRNAs, which has proven to be a significant challenge to the field. Since then, Abbott has set out to characterize microRNA function using two different rhythmic behaviors in worms — the defecation cycle and ovulation — as a way to identify how and when microRNAs elicit effects over normal processes.
it is a line that connects Evans’ work to that of another talented Marquette researcher. A stone’s throw away from Evans’ lab, Dr. Allison Abbott, in her research into how microRNAs regulate rhythmic cellular processes, has landed pay dirt in an unlikely place: worm poop. Abbott, an associate professor of developmental biology and genetics, is studying rhythmic behaviors in the worm C. elegans as a way to understand the functions of small RNA molecules called microRNAs. Abbott’s path into the study of rhythmic behavior was not planned. “We stumbled into it because we had a microRNA that was regulating the defecation motor program in worms, which involves a rhythmic calcium wave that regulates muscle contractions to expel the waste of the worms,” she says. Abbott elaborates on the current focus of her lab, adding, “We’re using this very simple model organism of C. elegans, the worm, to probe the functions of microRNAs.” The phenomenon of regulatory RNAs — though not necessarily new — blatantly interrupts the overly simplistic, so-called central dogma of molecular biology, a succinct paradigm that describes the flow of genetic information; simply stated, that DNA makes RNA, and RNA makes proteins. Stopping short of making proteins, the stereotypical final form of functional biological molecules, microRNAs have recently emerged as important, albeit
The defecation cycle — a series of coordinated muscle contractions that occur every 45 seconds in worms — is triggered by a wave of calcium that originates from one single cell. Abbott’s lab discovered that a microRNA regulates this process. Remove it and uncoordinated calcium release ensues, ultimately resulting in sporadic defecation cycles. Abbott points out the significance of microRNAs in this system, saying, “What’s really fascinating is this microRNA is regulating how one cell can act as the pacemaker for that system,” as she eludes to the potentially grand impacts of these small molecules in a wide variety of physiological processes, from development to heart function. Her lab’s second project, which is funded by the National Institutes of Health, examines the role of microRNAs in ovulation, a complex rhythmic system in which she found microRNAs to be essential. She aims to tease apart the precise role of microRNA in the process, determining the effects of altered microRNA levels and defining the exact type of microRNA involved and in which cells they are present. Abbott is optimistic in her pursuit of foundational knowledge about microRNAs and its value in rhythmic behaviors and beyond. “We’re at that simple level of trying to understand what they do normally in development and physiology, and we hope that extrapolates understanding what happens when they’re misregulated in human disease,” she says.
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