Project THE ROOTS OF ADDICTION

Ling's first toy was a microscope — not too surprising, since both parents are scientists. But the macro world drives her current research. "Drugs are talked about everywhere — the media, books, movies, drug education at school," she says. "I wanted to explore the mechanism of addiction" and why it varies so much from person to person. Her research also has implications for improving pain management with opium-derived drugs such as morphine and heroin.

harrison project
A slide outlining Pan's findings.
Ling, who was born in China, examined the genetics behind one of the body's three receptors for absorbing opium-type drugs: the mu-opioid receptor. MORs are widely scattered throughout the brain and nervous system. Since all MORs stem from one gene, called the Oprm gene, why do people react differently to opiate drugs?

The explanation is probably found in what's known as alternative gene splicing, or a slight rearrangement of a gene's sequences. Once, that would have violated a cardinal tenet of biology: one gene, one protein. But alternative splicing was documented for a number of genes in the 1980s — and for Oprm in the late 1990s. What happens, basically, is that the copy of the gene gets edited while being carried by messenger RNA, so a modified version arrives at the ribosome that produces the MOR protein from Oprm's recipe.

Working at Memorial Sloan-Kettering Cancer Center (where her father, Ying-Xian, is a researcher), Ling discovered six new "splice variants" from the Oprm gene. All six MOR proteins have identical shapes, but at one end, each has a different order of exons, the segments governing the expression of amino acids. When Ling tested her variants, she found dramatic differences in certain molecular functions.

These variations could be the roots of diverse reactions to opiates in humans. They may also be the key to new drugs for controlling pain or combating addiction. The first phase of Ling's research was published last November in Journal of Neurochemistry. Her full report is scheduled to appear in Journal of Neuroscience this spring.


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INTEL SCIENCE SEARCH FINALIST Ling Pan

Ling Pan


Essay:

Science Needs Women Scientists


Brearley School
New York, N.Y.


Hobbies: Violin (played at Carnegie Hall), art, photography, yoga


Ambition: Physician or medical research