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July 16, 2015
CHAPEL HILL, NC – Two labs at the UNC School of Medicine earned a four-year, $1.3-million grant from the W.M. Keck Foundation to build a “real-time map” of the events in the human cell cycle that are important for normal cell proliferation and development, as well as during diseases such as cancer.
The labs of Jean Cook, PhD, associate professor of biochemistry and biophysics, and Jeremy Purvis, PhD, assistant professor of genetics, will use live-cell fluorescence imaging to build the interactive map of the complicated molecular interactions that trigger and carry out DNA replication and chromosome separation – both key steps that lead to a single cell dividing into two. Such a map will allow the scientists to compare the cycles of different cell types, such as adult and embryonic cells.
The goal is to produce the first comprehensive, interactive cell cycle model that will be publically available so scientists can explore new relationships between cell cycle events, create hypotheses, and test treatments that target specific parts of the cell cycle.
“We know that the cell cycle involves a complex sequence of molecular events, but our current knowledge of it comes largely from snapshot measurements that can’t show us the underlying dynamics of those events, such as when exactly they happen in relation to each other,” said Cook, who holds a joint appointment in the department of pharmacology. “We plan to use an interdisciplinary approach to assemble the first real-time map of the cycle so that we and other researchers can better evaluate its importance to normal health and diseases.”
Over the course of four years, Cook and Purvis, who are both members of the UNC Lineberger Comprehensive Cancer Center, will create and validate a suite of novel fluorescent biosensors that will allow them to visualize the key events throughout the cell cycles of normal epithelial cells, stem cells, and differentiated cells – which descend from stem cells to form various organs and body parts.
With these new biosensors, the labs will use time-lapse microscopy and automated image analysis to track transitions within individual cell cycles. For the final step, the research teams will use a new computer algorithm developed in the Purvis lab to assemble the resulting image sequences and link together each of the cell cycle transitions into a continuous molecular timeline. That timeline will become the basis for a predictive model of the cell cycle that can be used to virtually test the effects of mutations or drugs.
“The cell cycle is one of the most basic biological processes, but our understanding of it is lacking because of the way we have been looking at it.” Purvis said. “It’s like trying to put together a photo album by gathering hundreds of pictures taken by different people from different angles. With this award, we will get the chance to make the first cell cycle movie.”
Jean Cook, PhD, is also the associate dean for graduate education at the UNC School of Medicine and the director of the Biomedical and Biological Sciences Program (BBSP)
The W.M. Keck Foundation, founded in 1954, supports the exploration of discoveries in science, engineering, and medical research.