Work of Four TSRI Scientists Contribute in Science Magazine's Top-Ten Breakthroughs of Year

By Jason Socrates Bardi

The work of four scientists at The Scripps Research Institute (TSRI) was cited by Science magazine among three of the journal's annual list of the top-ten breakthroughs of the year. The complete list appears in the December 20, 2002 issue of Science.

All four scientists are in the Department of Cell Biology at TSRI. In addition, three of the scientists are members of TSRI's Institute for Childhood and Neglected Diseases (ICND). The ICND was created to apply the burgeoning knowledge of genes and their interactions to understand, address, reduce, and treat specific childhood diseases, early-onset diseases, and "neglected" diseases, which affect populations primarily in developing countries.

The four scientists and their breakthroughs are:

Professor Steve Kay for "[work on] a new class of light-responsive cells in the retinas of mammals." Kay recently demonstrated that the gene Opn4, which codes for the protein Melanopsin, is the elusive pigment gene that captures light and keeps your body tuned to a daily cycle—called a circadian rhythm. "This is the key protein in the eye that sends signals to the clock," says Kay.

This research should help in the development of strategies for correcting sleep disorders, many of which are related to circadian rhythms. Furthermore, understanding the protein that resets the body's clock should help in research aimed at countering the most common circadian problems—the jet-lag one feels after overseas flights or fatigue when working night shifts.

Assistant Professor Ardem Patapoutian for discoveries that "helped explain why spicy food feels hot, and breath mints give the mouth a chill." Patapoutian identified and isolated a protein, called TRPM8, that mediates the body's ability to sense cold and menthol through the skin. TRPM8 is the first cold-sensing molecule that has ever been identified and may be an important basic target for pain-modulating drugs.

He also identified and cloned the first-known gene that makes skin cells able to sense warm temperatures by making a membrane protein, called TRPV3, that opens when it senses a temperature above a certain level and allows ions to pass through and cause an electrical potential that signals the brain. "This protein may be an important target for drugs," says Patapoutian, "because, like other TRP channels, it may be involved in inflammation and pain-mediation."

Assistant Professor Elizabeth Winzeler and Professor John Yates, who both contributed research in support of the publication of "genome sequence drafts for organisms with major agriculture and public health relevance for the developing world."

Winzeler found a way to use a relatively new but readily available technology to quickly detect markers in the DNA of the most deadly type of malaria pathogen. The technology could enable scientists and public health workers to identify the particular strain of malaria during an outbreak and determine if it is drug resistant or not. The work should also make it easier to follow the spread of drug resistance around the world, and to assist health ministries in countries where malaria is a problem to come up with strategies to thwart this spread.

"One of the reasons for the resurgence of malaria in Africa and in other parts of the world is the spread of drug resistance," says Winzeler.

Yates led a large effort to determine the "proteome" of the most deadly form of the malaria pathogen—Plasmodium falciparum. Knowing which proteins are expressed by Plasmodium falciparum should help scientists understand how the pathogen causes malaria and, with luck, how to thwart it. These efforts will pay huge dividends in global healthcare if even a few of the newly identified proteins lead to the development of new malaria vaccines—and Yates and his colleagues found more than 2,400 proteins.

"This is the first instance that I know of where these proteomics studies have gone along side-by-side with the genome sequencing project," he says.

The December 20, 2002 issue of Science is currently available at