Deerfield Magazine Spring 2013

By Stephanie Moeckel-Cole
Photographs by Brent M. Hale

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A couple of years ago three Yale undergrads and their classmates abandoned chilly New Haven in favor of a more tropical climate for spring break. Their destination had it all: lots of lush foliage, sandy beaches, warm waters, and at least 40,000 plant species . . . not your typical hot spot, but then again, these students weren’t typical spring breakers, and neither was their destination.

The trio was part of Dr. Scott Strobel’s “Rain Forest Expedition and Laboratory” course, and their mission was to collect indigenous branches, twigs, and microbes in the Amazon. Summer break would then be spent classifying their finds and identifying new bioactive compounds—exciting enough work for any bio prospector—but what the team of Anand, Huang, and Russell found was the equivalent of an old-time prospector’s gold nugget . . . they just needed Dr. Janie Merkel ’91 to help them make it pan out.

Not too many years ago Janie was a student herself, and part of what she fondly refers to as “Varsity Biology” at Deerfield, led by Andy Harcourt. In fact, the class was “Advanced Placement Biology,” and it was not for the faint of heart. “We had a particularly amazing class,” Janie says. “The rapport we built was so different than in other classes I’d had, in part because of the hands-on work we did together, but it was also just the dynamic of the group.” And perhaps the fact that Mr. Harcourt’s students bonded over the amount of work involved in covering a chapter a day in their textbook—no small feat, even for bio enthusiasts. Although Janie credits both Mr. Harcourt and her AP classmates for inspiring her, she does admit to wanting to be a scientist even before she came to Deerfield. “I once told my dad that I liked how science ‘told you all about the future,’ which made him chuckle because he never felt that kind of connection at all.”

After Deerfield Janie majored in Biophysical Chemistry with a minor in biology at Dartmouth, then headed directly to Yale for graduate school, followed by post-doctoral work at a non-profit research organization that focused on whole genome sequencing. “That was where I made my segue into technology and large datasets,” Janie says, “which prepared me to come back to New Haven for a Yale ‘spinoff’ that had developed a technology to figure out which genes were being expressed in organisms whose genomes were being sequenced, kind of before the fact. Then I moved to another Yale spinoff that had been acquired by a large biotech, founded on a technology that looked at interactions between proteins en masse.”

Reference Materials

BOK1-1024x682The net worth of all this was that Janie became adept at navigating new technology, large collections of data, and a broad customer base—a perfect background for the director of the Biological Division of Yale’s Center for Molecular Discovery. Today Janie manages a team of five scientists who bring their varied skills in research and their experience in the pharmaceutical industry to the projects they work on. As for the Center itself, well, “it’s unique” is a bit of an understatement:

While many facilities offer researchers access to state-of-the-art equipment and technology, Janie and her staff are a team of scientists who are willing to help through all stages of a research project . . . from initial design, to implementing the testing, to helping to interpret the results, to suggesting next steps. The process does not end with the development of experimental design, but continues to evolve as the discussion progresses from how to best evaluate the data being generated to how to best leverage the results. The Center also provides support to Yale researchers during their grant submission process, and to date has helped faculty members secure more than $13,600,000 in funding.

“It’s a bit like I imagine sending my children off into the world will be,” Janie laughs. “We help researchers with the part they can’t do, and then the project moves on without us.” All joking aside, Janie, her colleagues, and the Center provide incredibly valuable services—such as sterile liquid handling and robotic testing; this allows for larger scale experiments than are possible in most academic research labs, and a reduction in contamination and human error, leading to high reproducibility and results. In the world of science, these are worth more than gold.

BOK3The Center can also provide researchers with access to a wide variety of different types of screening options—from analysis on the level of molecules to more complex cell-—and organism—based assays, using techniques such as Small Interfering RNA (siRNA), sometimes referred to as ‘silencing RNA’ for its ability to turn specific genes on and off. There’s also a division that specializes in medicinal, computational, and synthetic chemistry, with experience applying their methods to multiple areas such as oncology, infectious diseases, and cardiovascular and neurodegenerative disorders.

If it sounds impressive, that’s because it is . . . and there’s more: In addition to assistance with managing technology and designing experiments, it wouldn’t be a stretch for Janie to add “science librarian” to her title; she and her crew offer researchers access to libraries that contain collections of tens of thousands of chemicals, siRNAs, and natural products. Just as a traditional library can hold thousands of books on many different subjects, genomics or chemical libraries contain copies of thousands of different genes or compounds—it’s quite a body of knowledge (BoK). By screening against this many genes or chemicals simultaneously, a researcher might identify several that are worth exploring further. There are several libraries available; some contain chemicals originally discovered by pharmaceutical companies, including known drugs that have been shown many times over to be useful for multiple diseases, and some are collections of chemical compounds made by Yale researchers. Others may contain arrays of natural products that were isolated from various rainforest organisms by Yale undergraduates—undergraduates who spent their spring break in the Amazon.

Research Strategy

After her trip to South America, Pria Anand decided to see if the endophytes (fungi) she collected could be used in bioremediation—simply put, if they could break down garbage. Anand was able to show that a chemical reaction did take place when one of her endophytes was introduced to plastic. Fellow student Jeffrey Huang furthered the research by analyzing additional endophytes that were gathered on the same trip to find those that broke down chemical bonds most efficiently, and finally, Jon Russell isolated one family in particular that showed the most promise for bioremediation. He then went on to identify the enzyme that worked the best on polyurethane—that polymer that is used in everything from skateboard wheels to spandex bike shorts. Polyurethane is extraordinarily tough, which is great when a manufacturer wants to make a durable product. The downside is that polyurethane doesn’t readily decompose, and literally tons and tons of products made with it can be found in landfills throughout the world. If the Yale students’ discovery could efficiently degrade this plastic, that would be significant.

Well developed research abilities aside, it was a classic “no brainer” for Jon Russell to bring his work to the Center’s Biological Division; even his professor, Dr. Strobel, referred to it as “one-stop shopping for scientists who are looking to take the next step in advancing their research.” The Center is also known for bridging the gap between discovery and the involvement of those who have the funds to take initial results to the next level—be it pharmaceutical companies or other investors. It doesn’t hurt that the Center has the ability to move a laboratory investigation along rapidly—something unique in an academic setting—processing tens of thousands of samples a day, thanks in part to those libraries of information Janie helps to curate.

BOK4The Center’s collaborative method is another unique feature; once a project such as Jon’s is selected, the researcher is paired with a member of the Center’s staff, and they take up the investigation together. While high tech tends to be modus operandi, every now and then low tech gets the job done—or at least the Center’s version of “low tech.” Janie suggested a trial to Jon that was almost reminiscent of an art project she might do at home with her young daughters—it involved plastic beads and brightly colored dye, and a deceptively simple process: “I suggested to Jon that he use polystyrene beads impregnated with dye that would release if the beads started to decompose.” Keeping in mind that we’re talking about miniscule amounts of matter breaking down, Janie also advised Jon to filter the media that housed his experiment in order to separate liquids from solids. “There are other ways to test for plastic degradation but the dye-based method relies on fluorescence—the emission of light—which allows us to detect even small levels of degradation,” she said.

But how exactly does a tiny fungus have the strength to break apart something as substantial as polyurethane? For starters, “fungus” does not equal “green slime” as one might imagine, and in the world of fungi, “tiny” does not equal “feeble.” “Basically,” says Janie, “the fungus produces an enzyme. Think of a tiny, specific machine, like a drill, that takes one kind of input and makes one kind of hole. In this case, the enzyme breaks a bond in polyurethane to produce smaller pieces, that can then be broken down by another enzyme for another bond type, and so on.” To put it mundanely, Russell and his classmates had discovered an all-natural demolition crew.

“If you want to have any chance of discovering something new, flexibility and creativity are key!” says Janie. “We are doing science in a faculty/student-centric way simply because of the wide variety of projects faculty researchers and students bring to us; we really need to be flexible to adapt and help them all. My team members have different professional experiences, and that fuels our collective creativity. One of the great parts of our work is that not only is it creative, it is testable and quantifiable; those who come to us can put their innovative ideas in the crucible, so to speak.” Then she adds, “Personally, I would love to do more work with ecological or environmental benefits, so it was a real treat to work with Jon.”

While the Center primarily serves the needs of researchers within the university, it is also open to outside researchers from other academic institutions or industry, and the nature and scope of those projects is just as extensive as Yale’s own: One project involved the investigation of potential synergistic effects when combining two drugs to fight multiple cancers, and found encouraging results for the treatment of resistant melanomas. Another recent project found a molecule that has the potential to be used to diagnose a form of kidney tumors, which happen to be easily treatable, but currently difficult to detect until they are highly advanced. A third group made some great progress in developing a molecule that can be used to treat clotting disorders. Altogether in 2012, the Center was involved in a total of 87 different research projects—an impressive variety to be flourishing in one single facility—and Janie considers herself fortunate to be in the middle of this hotspot of scientific discovery.

BOK5-e1367247346646“Part of what makes my work so enjoyable is the fact it’s always fresh and exciting—new ideas and new discoveries,” she says. She is also realistic about her work: “It is a long path between finding a molecule and treatment for a disease,” she acknowledges. Or discovering an enzyme that can reduce the mass in our landfills? “Exactly. In the case of working on a new drug, there’s typically a high level of involvement and commitment with pharmaceutical companies eventually; this is where testing drugs already available for ‘repurposing,’ such as those in our libraries, can really kick start a project, because a wealth of data regarding safety, side effects, and so on already exists; a faculty member can take a project further quickly, with higher likelihood and success in engaging a pharmaceutical partner. I’m glad we can build upon existing knowledge.”

Endnotes

Since working with Janie, Jon Russell, his classmates, and their fungus have received some good press: Popular Science held it up as another argument for protecting rainforest biodiversity, and Russell et al had a paper about their discovery accepted by the journal Applied and Environmental Microbiology . . . but you won’t find Dr. Janie Merkel’s name in the credits. “The continued research has moved elsewhere,” Janie says. “The way we work with the researchers taps into so much valuable knowledge, promotes engagement, and serves a critical role in the education of our fellows and students—we are often the starting point and we provide the opportunity to gain hands-on experience. Then our researchers move on.”

Janie pauses and then says: “It strikes me, as the mother of two young girls, that there is an ever increasing pressure to specialize and master skills early. But how do you know that what you are specializing in is something you like or are good at unless you have some decent comparators? I see this frequently in lab research; breakthroughs occur when people think more broadly, jump in, learn from what others are doing, and then improve it. It will be truly exciting when a chemical we found and modified or found and out-licensed really impacts the Earth or human health. I don’t know how close we are to that time, but it will happen.” And when it does, you can be sure Dr. Merkel was there to lend a hand. ••

Dr. Stephanie Moeckel-Cole is a scientific researcher studying the effects of chemotherapy on the bone density of breast cancer patients. In addition to her research, Dr. Moeckel-Cole teaches Introductory Biology at Holyoke (MA) Community College and anatomy and physiology at UMass-Amherst. She lives in Deerfield with her husband and two children.