Philip Borer, professor of chemistry and biophysics in The College of Arts and Sciences, prepares samples for nuclear magnetic resonance imaging in the basement of the Center for Science and Technology.
hen Philip Borer began studying RNA molecules at the University of California, Berkeley, in the late sixties, he wasn't thinking about the good of humanity. As a graduate student working with one of the first groups to seriously study molecules of ribonucleic acid, his interest lay in the pure study of the intricate strands of genetic material. "There's this beauty of design in these molecules," says the professor of chemistry and biophysics in The College of Arts and Sciences. "There's the joy of discovering things and looking where nobody else has."|
Thirty years later, Borer and a team of researchers from Syracuse University and the University of Maryland-Baltimore County (UMBC) looked where nobody else had looked and found the key to a new weapon against HIV (human immunodeficiency virus), which causes AIDS. The team produced a detailed model of the virus's protein-RNA packaging complexthe interaction between small protein molecules called nucleocapsids and RNA molecules that enables the virus to reproduce. Armed with this model, pharmaceutical companies can develop drugs that interfere with the process, thereby preventing HIV from spreading.
"I've been interested in HIV ever since the first details came out about the virus in the early eighties," Borer says. "But I never really did any work on it until 1995, after I went to a scientific meeting in Colorado and listened to Mike Summers give a talk about the protein part of this packaging complex."
Summers, professor of biophysical and bioinorganic chemistry at UMBC, had been trying to get a detailed look at the protein-RNA complex since finding the structure for the protein in 1992. The RNA molecule, however, eluded him and other researchers. "These things are not commercially available," Borer says, "so somebody who has the background to do it must make them." Borer had the background and offered to synthesize the molecule in his laboratory at SU, where he had been working since 1983. Summers gladly accepted the offer.
Retroviruses like HIV use RNA as a template to make new proteins the virus needs, Borer explains. The nucleocapsid protein binds to an RNA fragment and drags it to the outer edge of an infected cell where it buds off to make a new virus containing the RNA genetic material. Borer and his researchers predicted a part of the RNA molecule called SL3 was a likely candidate for the packaging complex. "Actually, the rules used for those predictions are things I worked on when I was a graduate student," Borer says. "This was familiar territory."
Research assistant Lucia Pappalardo, an SU doctoral student in biophysics, used nuclear magnetic resonance (NMR) to plot the three-dimensional structure of the molecule. "Synthesizing RNA was something new for me," says Pappalardo, a native of Torre del Greco, Italy, who came to Syracuse partly because of its NMR facilities. "It was both a challenge and a chance to work on part of the HIV virus." Once finished, she sent a sample to the UMBC lab, where researchers successfully combined it with the nucleocapsid. The results were published in the January 16th issue of Science magazine.
"What we have now is a magnified view of the parts of the RNA and protein that interact with each other to form this packaging complex," Borer says. "Having that picture, a pharmaceutical company could design a molecule that has a similar shape to the SL3 or nucleocapsid parts, and then interfere with making this complex. That would either slow down or stop reproduction of the virus in a person infected with HIV."
HIV tends to mutate rapidly, Borer notes, and may soon be resistant to the two major AIDS drugstranscriptase and protease inhibitorseach of which attacks a different part of the virus's life cycle and are used in combination. "We hope that from our work people will develop drugs that attack a third, completely different part of the virus's life cycle. It's unlikely the virus will simultaneously mutate out from under three different factors."