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DNA Scrunching, Video Games, Smart Drugs

Published on March 4, 2016 in Cornerstone Blog · Last updated 4 months 1 week ago


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Welcome to another roundup of CHOP research in the news! This week’s stories from The Children’s Hospital of Philadelphia include the use of big data to understand a tiny molecular mechanism central to how cells function, a clinical trial of video games for improving attention, and the neurodevelopmental effects of so-called “smart drugs.”  

Big Data Algorithm Aids Discovery of “DNA Scrunching”

A bioinformatics group from CHOP collaborated with researchers from Rutgers University to uncover details of an essential process in life: how a crucial enzyme locates the site on DNA where it begins to direct the synthesis of RNA.

“The algorithms we developed enable us to tackle many questions across diverse areas of DNA and RNA biology,” said Deanne Taylor, PhD, director of bioinformatics in the Department of Biomedical and Health Informatics at CHOP and research assistant professor of Pediatrics at the University of Pennsylvania. “Understanding these fundamental processes may help in developing antimicrobial treatments to fight bacterial disease.”

Dr. Taylor co-authored the study, which was published online this week in the journal Science.

In the study, Dr. Taylor and Yuanchao Zhang, a graduate student working with her bioinformatics group at CHOP, developed big-data algorithms to analyze sequencing data output from new experimental approaches developed by the CHOP/Rutgers team. These chemical and biochemical approaches generated vastly more data than previous methods, enabling this new discovery.

In their work with bacteria, the team found a next step that occurs after the enzyme RNA polymerase binds to DNA and partly unwinds the two strands of the DNA helix to begin translating DNA into RNA: The enzyme then continues unwinding those two strands, pulling the unwound DNA strands into itself until it engages the transcription start site. The researchers call this process “DNA scrunching.”

Read more in the CHOP press release.

Clinical Trial for Video Games

What could be a more appealing prescription for children with autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD) than a doctor’s order to play video games? It is too soon for video games to be part of standard therapy, but researchers are evaluating one game’s potential for improving attention.

“When you look at the landscape of games, so far, there have been a lot of empty promises,” Benjamin Yerys, PhD, told the Portland Tribune. “The data has not lived up to what we hoped for.”

Dr. Yerys, a psychologist at the Center for Autism Research at CHOP, is conducting a clinical trial of a game called Project: EVO, designed for children with ADHD. If it works, it could be especially valuable for children with both ASD and attention deficits, because only about half of this population responds to ADHD drugs — and those drugs come with side effects for many kids.

Solid evidence of the game’s clinical effectiveness, like the evidence needed for effectiveness of a medical device, will be required for U.S. Food and Drug Administration approval of the game as a therapy. Read more about EVO, and about why gathering this evidence will be challenging, in the Portland Tribune.

Getting Smart About Smart Drugs

ADHD drugs were also in the news this week for a controversial off-label use: neurological enhancement. A feature article in Nature highlighted the issue of healthy individuals, especially teens and young adults, taking drugs such as methylphenidate (Ritalin), amphetamine (Adderall), and the sleep-disorder drug modafinil (Provigil), without a prescription in an effort to boost brainpower or attention.

Kimberly Urban, PhD, a postdoctoral fellow at CHOP, commented on the limited evidence to date on long-term effects. She noted that these drugs target the neurotransmitters noradrenaline and dopamine, which are critically involved in teenagers’ brain maturation. Although the drugs do not seem to cause problems in teenagers with ADHD, it is unknown how they might disrupt the development process of other teenagers’ brains. Her past research in a small animal model indicates that methylphenidate might translate to problems with working memory and flexible thinking, if the effect holds true for humans as well.

Read more about the science of smart drugs in Nature.