By Sarah Welsh

Cancer starts with a single cell going haywire. What is it about that one cell that makes it different from the rest, setting it on a path of destruction? A new program at the University of Pennsylvania may help find an answer to that and many other questions.

The Penn Program in Single Cell Biology is a new effort by faculty members James Eberwine and Junhyong Kim to understand biology as it happens in each individual cell. Founded late last year, the PPSCB is supported by Penn’s Perelman School of Medicine and Institute for Translational Medicine and Therapeutics.

Eberwine, the Elmer Holmes Bobst Professor of Pharmacology in the medical school, and Kim, the Patricia M. Williams Term Professor in Biology in the School of Arts and Sciences, co-direct the program. They have worked together for decades trying to understand what makes each cell different from one another.

“As humans, we have about 100 trillion cells in our body,” Kim says. “Up until now, people have thought about these cells as just building blocks that make up the body. We know that brain cells are very different from heart cells, but traditionally we don’t think about the individual heart cells: are they all doing the same thing or are they all doing something different?”

The Center is sponsored by the National Institutes of Health Single Cell Analysis program and is one of only three such centers worldwide. Each is focused on a different type of cell and employs a different type of technology to study cells individually. PPSCB’s emphasis is on heart and brain cells, and scientists there particularly interested in studying the RNA material in these cells, which can give clues to their function.

Kim, a computational biologist, and Eberwine, a molecular biologist, have a mutually beneficial partnership: Eberwine’s lab performs the molecular biology bench work while Kim’s lab helps analyze and interpret the data.

A single cell is very small; an average neuron is smaller than a grain of table salt. The DNA and RNA molecules that the PPSCB researchers are trying to detect within that neuron are even tinier. Typically, DNA and RNA sequencing is done with many cells at once from, for example, a piece of hair or blood sample. Trying to sequence the genetic material from a single cell, on the other hand, as the PPSCB is doing, requires sequencing many cells individually, using sequencing technologies that have traditionally been very expensive.

“We are making measurements really at the limit of what we can measure,” says Kim. “Some of the techniques Jim has developed in the past 20 years have allowed us to make these measurements, and, importantly, the cost of sequencing has come down.”

The other difficulty with the types of sequencing experiments the PPSCB is embarking on is the amount of data generated. The computational analysis the researchers must do to interpret the data is anything but straightforward. That means a good portion of the center’s work is done on the computer rather than the lab bench. 

“You can’t just look at the data without doing computations because there are billions of datapoints,” Kim says.

Researchers used to assume that cells taken from the same tissue type would be effectively identical, but Eberwine and Kim have found significant differences in the RNA content between individual cells. This suggests that individual cells are preparing for different functions by regulating which of their genes are expressed and to what extent they are expressed.

A major goal of PPSCB is to grow awareness of single cell techniques at Penn so other researchers can begin to ask new biological questions. Kim says that many labs studying cancer are very interested in using new single cell techniques. Tumors are made up of a hodge-podge of erratically growing cells that are very different from each other. Learning about the differences between the individual cells in a tumor can help researchers understand how to better treat cancers.

PPSCB is hosting a variety of workshops and a symposium this spring aimed at helping Penn scientists learn how to apply these single cell techniques to their own labs.

“These workshops and courses are vital to the mission of PPSCB because they provide hands-on experience with this technology, which can be tricky to use,” Eberwine says.

In addition to hosting workshops, creating symposia and developing technologies, PPSCB will also be making grants for Penn researchers who want to utilize single cell technologies in new ways.

“I’d like to see this program allow more people to use the technology, and provide funding for the creative ideas the faculty and students have,” Eberwine says. “We have to enable people’s creativity to get new experimental answers.”

Additional information about the program and spring meetings is at http://kim.bio.upenn.edu/ppscb/.