by Colleen Carey

High school student Jessica Allen e-mailed Rensselaer professor Christopher Bystroff with a question about protein folding last year. This year, she is doing research with him.

Allen, an upcoming senior at Walter Panas High School, and Bystroff, assistant professor of biology, started constructing a database last November to help learn what causes amyloid diseases, such as Parkinson's and Alzheimer's disease.

A self-motivated student, Allen's fascination with biology started with her first biology class.

“It’s interesting to see what little mechanisms make up the body,” she said.

Her school in Cortlandt Manor, NY participates in a Science Research Program. Allen gets college credit for her work, which began her sophomore year.

She started out with forensics as her research topic, but didn't turn up a lot of scientific research and the experts she tried to get in touch with were unresponsive. Then she read an article on protein folding in the New York Times, where a researcher linked it to Alzheimer's disease.

She later switched her topic and e-mailed Bystroff.

Bystroff says he gets email from inquiring students all the time. After he answers their questions, he doesn't hear from some of them again.

“But sometimes they keep asking. Jessica kept asking,” he said. And it led to a working relationship.

Bystroff asked Allen to find all the mutations concerning amyloids in the Genbank database, an annotated collection of all publicly available DNA sequences put out by the National Institutes of Health.

With this information, they are compiling and putting together a curated database to learn what causes amyloid diseases.

Amyloid is a waxy, translucent substance consisting primarily of protein. When proteins misfold, amyloid plaque can be deposited in some organs and tissues. Neurodegenerative diseases such as Alzheimer's, Parkinson's, and Huntington's disease are amyloid diseases.

As far as Bystroff knows, no such database exists.

“People tend to focus on individual mutations,” he said. But this project helps see the big picture.

A curated database has less redundancy than a primary database and has the added value of scientific annotation. So, a biologically significant sequence should be easier to locate and is of greater value.

To fill out the database, Allen started off by making the Genbank searches, and then put the sequences she found into a BLAST (Basic Local Alignment Search Tool) search. From there she was able to use the HMMSTR program, written by Bystroff, to predict the structures of proteins from the sequences.

"Hopefully, I can work on it until it's complete," Allen said. Bystroff says that if they find a definitive result, they could publish in a year. Any timeline, however, is hard to pin down.

Later on in the process, Wilfredo Colón, associate professor of chemistry and chemical biology, will be involved in some experimental testing. They will make a mutation in the protein to see if it forms amyloid plaque – fibers that can actually be seen under florescent light.

Allen and Bystroff have been working together since November 2003, mostly over email, but this week she got to come to Rensselaer to work in his lab.

The project is bigger than what Allen initially imagined.

"This (project) is always challenging. There is always something new to research," she said.

Her favorite part was coming to RPI and working in the lab, saying that it just feels more hands-on.

Bystroff likes the dedicated time that Allen brings to the project, unlike many college students, who often have huge workloads to contend with.

Allen, a Rensselaer Medal winner, is considering RPI for college. This project gave her the chance to see the campus, experience a laboratory environment and facilities, and to work on real research.

“This is real research. We don't know the answer. If we knew how it would turn out, then we wouldn't have to do it," Bystroff said.

Allen's father Paul Allen, who is a Rensselaer alumnus, Computer Science '82, says that the program has given his daughter some great opportunities.

When Allen first got involved with protein folding, she learned of a group called The Protein Society. Because she is getting college credit, she was considered a college student and could attend their annual symposium in Boston last year (a symposium Bystroff attended as well).

"I didn't understand everything," she said, "but enough."

Published September 3, 2004