Synthetic Biology, Real Commitment

Synthetic Biology, Real Commitment

Commitment is a given for scientists. Among all the characteristics commonly associated with scientists, perhaps the trait of focused commitment holds the most truth. You simply cannot obtain a Ph.D. from a reputable institution without long hours alone at the laboratory bench, in front of a computer monitor, or out in the field. But it takes real commitment to cling to a line of research when government grants are hard to come by and even your colleagues raise their eyebrows at your work.

Susan Janicki, Ph.D.

As Wistar’s Susan Janicki, Ph.D., describes it, commitment — to an almost-obsessive degree — is what has helped her persevere in research. “It was a struggle to get off the ground,” admitted Janicki. “But you can’t do it half-way and you don’t get credit for partial effort.”

Janicki, an assistant professor in Wistar’s Molecular and Cellular Oncogenesis Program, studies how cells regulate genes, that is, how they control which genes are turned on or off at a given point in time. By a wide margin, gene regulation is not an uncommon line of research among researchers at Wistar. How Janicki does it, using the tools of synthetic biology, is what makes her efforts both innovative and risky. 

In the infant field of synthetic biology, researchers create systems that do not exist in nature for the purpose of simplifying them or designing new functions. In essence, the technique uses a single cell as a living laboratory. While the approach has been used extensively to study genetic circuitry in yeast and bacteria, mammalian cells, like our own, are much more complex, which has led to some degree of skepticism of the approach amongst the biomedical community. 

According to Janicki, single cell synthetic biology allows you to look into individual cells and see how they operate directly.  To do so, however, requires a combination of genetic engineering with advanced mathematics. A researcher could, for example, add a reporter signal — such as green fluorescent protein — to a particular factor and watch how events within the cell interact dynamically with a gene, tracking the resulting glowing green protein as it moves throughout the cell. 

“Most of our understanding of molecular biology involves, essentially, freezing a moment in time by taking a molecule, purifying it, and studying it,” Janicki said. “It is certainly useful, but it only provides a two-dimensional representation of a three-dimensional thing. I want to see how a given protein operates in real-time as it moves through space.”

Single-cell research is not easy work, and each study presents its own set of technical challenges. The potential of these techniques, however, is vast. Not only can single-cell studies uncover the genetic origins of disease, they could provide a real-world testing ground for theoretical therapies or even designer test beds for new drugs.

For Janicki, her future goals were not always so clear. Like many biology undergraduates, Janicki left college with a degree but not much laboratory experience. To gain experience, she took on a job as a laboratory technician for a researcher at the University of Maryland before enrolling in a doctoral program in human genetics. In 1999, she became a postdoctoral fellow in the laboratory of David L. Spector, Ph.D., at Cold Spring Harbor Laboratory, and it changed her life.  

 “First off, Cold Spring Harbor hosts dozens of scientific events and conferences throughout the year, and anyone could attend. It was a constant stream of new ideas,” said Janicki. “With the techniques developed in the Spector lab, I was able to look directly into a living cell and see what was going on. I was hooked.” 

In 2005, Janicki accepted an offer to join The Wistar Institute where, she says, she has struggled to gain funding. It is the challenge of every young faculty member to develop their own sources of research funding through the National Institutes of Health, and it is the breaking point of many careers in science. It is particularly difficult when your work challenges the status quo, and her young career as an independent scientist was at a tenuous point when funding finally came through in 2010.

“The funding climate is terrible right now, and I was fortunate to have an NIH program director who really saw the promise in my work,” Janicki said. 

Now, as a federally funded researcher and new scientific director of Wistar’s Microscopy Facility, Janicki strives to partner with her Wistar colleagues in applying single cell and synthetic biological techniques to their research.  

“I like the idea of taking this work into the tumor microenvironment, and collaborating with my [Wistar] colleagues like Meenhard Herlyn,” Janicki said. “The possibilities are inexhaustible, but you need to get the cells to work. And that takes commitment.”