A Sphinx Among the Lipids
Robert Bittman begins his popular lecture on "Cholesterol and Other Lipids: The Good, the Bad, and the Ugly" with a quick look at how these biochemicals are turning up in the news. He cites the many Nobel Prizes awarded for work with lipids, and the controversy surrounding the lipid androstenedione, the steroid hormone used by the baseball star Mark McGwire.
But you don't need to consult the headlines for evidence of "the power of lipids," says Bittman, a Distinguished Professor of Chemistry, Biochemistry, and Biology at The Graduate School and Queens College. They are, after all, one of the three principal structural materials--with carbohydrates and proteins--of living cells. Lipids are a class of natural compounds that includes fats and cholesterol, and are defined by the fact that they are soluble only in such organic solvents as ether, chloroform, or benzene.
One of Bittman's own current research projects involves sphingolipids, a class of lipids identified a century ago. Sphingolipids, first identified in human brain tissue, were named after the Sphinx because their biological function was an enigma. But in the last decade, they have begun to reveal their secrets.
Bittman's project with these compounds began with an investigation of one of their destructive activities: their role in the process by which alphaviruses enter cells. Alphaviruses, which are the cause of several animal diseases, can give humans a fever, a rash, and arthritis-like symptoms. Called "enveloped" viruses because they are bounded by a membrane--in this case, a membrane two molecules thick and composed of lipids and proteins--alphaviruses attach to the outside of the cell membrane. Then a process called fusion occurs: Two particles, the virus and a compartment of the cell called an endosome, become one. The virus's RNA then replicates and takes over the host cell.
A crucial question is how the viruses undergo fusion with the cell. Scientists have long known that glycoproteins on the cell surface serve as receptors to alphaviruses, binding them with the cell. Now Bittman and his colleagues Jan Wilschut at the University of Groningen in the Netherlands and Margaret Kielian at the Albert Einstein School of Medicine have discovered that the next step, fusion, requires a co-receptor within the cell, on the endosome surface--and the co-receptor is a sphingolipid.
In order to study fusion at the molecular level, Bittman and two Queens College colleagues, Hoe-Sup Byun, a postdoctoral research associate, and Linle He, a graduate student in the Ph.D. Program in Chemistry at The Graduate School, have synthesized analogs of the sphingolipids that allow the virus and the target cell to fuse.
This project is supported by the National Institutes of Health. Along with providing science with a tool for studying the infection process, these analogs made in the Queens College laboratories may be a first step toward harnessing another of the sphingolipids' powers. In the future, the team hopes to make yet another synthetic sphingolipid--one that will block the natural sphingolipid's ability to fuse virus and cell.
If Bittman and his associates at Queens College are successful, the science of preventive medicine will have a new tool: The new, synthetic compound would be a new type of antiviral drug, offering immunity to alphaviruses.
