Associate Professor of Physics Allen Price was recently awarded a three-year, $378,754 grant from the National Science Foundation (NSF) to investigate how proteins find specific locations in DNA.
The grant, and the research, marks the continuation of a decade-long project that began with an initial NSF grant in 2012 and another in 2017, for a total of nearly $1 million.
Through their research, Dr. Price and a team of undergraduates have worked to understand how cells access genetic information and how they use it.
“We’re miles ahead of where we were a decade ago,” Dr. Price said. “When we first began, we weren’t even sure how to study this, so we spent some time just developing methods.”
Through these methods, the team studied the time proteins take to find their target sites and tracked the real-time motion of individual proteins during search. They discovered these proteins spend a significant amount of time sliding along DNA to find a “needle-in-a-haystack” location among the more than three billion base pairs in the human genome. The specific proteins studied cleave DNA into two strands when they bind to their target site. This process is a crucial step in gene editing and antibody production and a greater understanding of what instructs cells at different times could be particularly helpful in the treatment of genetic diseases and more.
They also unexpectedly found that proteins, while sliding, appeared to be pausing during target search, as if double-checking, before moving along the sequence. Through this observation, the team was able to map pause sites in the genome and identify the genetic signature of these sites, which differed in a single base pair from the target site. In addition to tracking movement, the team also noted that proteins are able to bypass roadblocks that obstruct search, by hopping or jumping over the obstacle. Other areas of interest for the group are “off-target” sites, which are similar to the target site and may slow target search or create off-target activity, with perhaps unintended consequences for genetic regulation or gene editing.
Over the past decade, Dr. Price’s research team has consisted of more than two dozen students, from all disciplines in science. In addition to training in cutting-edge biophysical laboratory techniques, the team has presented their work at national scientific conferences, including annual meetings of the Biophysical Society in San Diego, San Fransisco, New Orleans and Baltimore and authored more than a half dozen papers, published in prestigious journals such as PLOS ONE, American Journal of Physics, Biophysical Journal, Analytical Biochemistry, Journal of Visualized Experiments, and Biochemical and Biophysical Research Communications.
The group is still closely-knit, Dr. Price said, gathering for yearly laboratory reunions, both so alumni can learn about the team’s progress and current students can network with graduates who have entered the profession or are pursuing higher education.
Many graduates of Dr. Price’s NSF-funded research teams have gone on to work in research and medicine, including Briana Mousley ’15, who is working as a general surgery physician assistant at Brigham & Women’s Hospital; Elsie Helou ’15, a registered nurse at Boston Children’s Hospital; Lindsay Cathcart ’17, a dental resident at the Providence VA Medical Center and graduate of the Boston University School of Dental Medicine; Raquel Ferreira ’18, a medical student at the Lake Erie College of Osteopathic Medicine; and Emily Matozel ’20, a research associate at the Dana-Farber Cancer Institute. Janelle Welton ’16, is a Ph.D. candidate in the molecular and cellular biology program at University of Massachusetts, Amherst; Sadie Piatt ’18 is earning a Ph.D. in biophysics at Harvard University; and Anna Ware ’19 is a Ph.D. candidate in tumor biology at Georgetown University.
Dr. Allen Price
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