Go to navigation (press enter key)

News

Investigating p53, the Tumor Suppressor

According to the Cancer Research Institute, cancer is still the second leading cause of death in the U.S.   Hundreds of thousands of researchers worldwide are actively engaged in the effort to understand and combat the disease—including three Vassar students who are using some novel approaches to investigate the disease at the molecular level.

Visiting assistant biology professor Kelley Thayer in front of a computer-generated image of p53 with URSI students: Benjamin Slaw '15, In Sub Han '15 and Taylor Quinn '15 / Photo by Buck Lewis

The students, chemistry majors Benjamin Slaw ’15 of Tarrytown, NY; Taylor Quinn ’15 of Jackson, NJ, and In Sub Mark Han ’15 of Queens, NY, are trying to determine how a certain protein, called p53, helps the body prevent cancerous tumors from growing.   They’re working on the problem with visiting assistant chemistry professor Kelly M. Thayer under the auspices of Vassar’s Undergraduate Research Summer Institute.

When the p53 protein binds with DNA molecules, Thayer explains, it sends instructions to damaged cells to stop multiplying. But when this protein mutates, it often loses the ability to send this message, and the cells multiply rapidly. The result: a cancerous tumor.

Finding a drug to interrupt this process and stop the tumors from growing would be relatively easy, Thayer says, if all DNA molecules had the same pattern. But since DNA has multiple patterns, researchers must identify all of them and then figure out how each one interacts with p53. Slaw, Quinn, and Han have identified at least four other DNA patterns, and they’re carrying out computer-generated simulations to learn how the p53 mutants interact – or bind -- with each of them. “We won’t be able to develop an effective drug until we learn about the interactions with all the different patterns of DNA,” Thayer explains.

If they can answer these questions, the students may be able to help other scientists develop drugs that will prevent this chain reaction from occurring. “The goal is to be able to design a drug that can serve as a sort of molecular prosthetic between the mutated protein and DNA’s plethora of patterns so the rapid multiplication of cells doesn’t happen,” Thayer says. 

Thayer says she and the students plan to submit several papers on their findings to a scientific journal in the fall. “We’ve already found things no one else has found and we’re doing things to analyze the data no one else has done,” she says.

While scientists have assumed DNA had more than one pattern, no one had ever analyzed these patterns and figured out how each of them would bind with the mutated protein, Thayer explains. “We are finding that there are multiple means of binding, and this is exciting because it suggests a novel angle to tackle the problem,” she says.

Once scientists understand how all of these bindings take place, they can develop an anti-cancer drug that is effective for all DNA patterns. “This is a more formidable challenge, but it also sheds light on ways of improving scientists’ understanding of how the system works,” Thayer says. “The discovery makes it more likely we’ll be able to develop more effective drugs for cancer patients in the future.”

The students say they discovered early in their research that the work they’re doing this summer differs markedly from much of what they do in the classroom. Quinn is investigating how zinc atoms facilitate the binding of the protein with the DNA.

 “In class, you’re presented with problems, but somebody knows the answers,” she says. “What I’m doing this summer is asking questions that nobody knows the answer to. This is real-life science.”

Slaw says his first hurdle was debugging some of the new software he, Quinn and Han are using for the project.  “The simulation system we’re using isn’t just new to us, it’s new to the college, so we’re finding bugs and fixing them,” he says. “This isn’t just helping us in our research. It’s helping everyone on campus who will use this software in the future.”

Slaw says he’s trying to determine how DNA with different patterns interacts with the p53 protein, and to do that he had to write a new program that would build the computer-generated models of the molecules. “This enables me to build these structures in minutes instead of days,” he says.

One of Han’s tasks is analyzing three amino acids that act as binding agents between the protein and the DNA. To aid in that research, he created a “point system” rating how well each amino acid performed. Like Slaw, Han says he too had to find a way to create a measuring system that hadn’t been built before. “What I like about being able to do research full time this summer is you can dedicate all your time to overcoming obstacles. It’s literally: ‘OK, how do I figure this out?’” he says.

Han says it’s gratifying to know he and his fellow students are making discoveries that could someday lead to the development of effective anti-cancer drugs. “I’ve done some original research before but nothing on this scale,” he says. “We’re finding ways of looking at this that no one else has found, and in doing so, we’ll be helping other scientists who are doing cancer research. We’re contributing, this summer, to the bigger scheme of things.”

--Larry Hertz

Posted by Office of Communications Monday, July 14, 2014