Tracking Cancer with Chemical Tools

AMHERST, Mass. – Michelle Farkas, professor of chemistry at the University of Massachusetts Amherst, was recently awarded a $1.25 million grant by the National Institutes of Health to develop next-generation tools to track and manipulate circadian rhythms in cells, helping researchers to understand the role that such rhythms play in disease.

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The circadian clock is an internal system that helps the body respond to the time of day. Circadian clocks help regulate a number of different processes in the human body, including sleep-wake cycles, body temperature, blood pressure, food intake, hormone release, cardiac function, immune responses and metabolism. On the cellular level, circadian clocks also play a role in cellular proliferation, metabolism and DNA damage repair. Though researchers have known for years that changes to the circadian clock’s daily rhythms can lead to all sorts of diseases, including various cancers, we don’t yet know exactly what is going wrong at the cellular level when the circadian clock is altered.

“We can generate static snapshots of a cell,” says Farkas, “but they don’t tell you all that much. We need tools to help us track the dynamic changes occurring inside a cell over time.” Only then can researchers begin to see what happens when the circadian clock is altered

Farkas’s team plans a two-pronged approach over the next five years. First, they will develop new methods of tracking the production of proteins—the cell’s building blocks—including in cases of altered circadian rhythms. To do this, Farkas and her colleagues will continue to develop tools, which will allow researchers to watch as proteins are generated by multiple genes at the same time. “These next-generation tools, called ‘reporters,’ will let us track the process for different components, giving us a clearer, more complete picture.”

Farkas and her colleagues are also generating new approaches to “perturb,” or alter, the circadian rhythms of the cells by directly targeting the core circadian proteins. By using their reporters to track the proteins that are at the heart of the cell’s circadian clock, the team will be able to alter circadian rhythms and watch how cells respond—including responses that lead to the development of cancer.

“Cancer is a complicated, dynamic process,” says Farkas, whose lab at UMass Amherst is supported by the Institute for Applied Life Sciences (IALS), which combines deep and interdisciplinary expertise from 29 departments on the UMass Amherst campus to translate fundamental research into innovations that benefit human health and well-being. “We need systems, like the one we’re developing, to track its development.”