As a fellow at Harvard, Ptashne rose to fame after isolating the repressor of lambda phage virus. The lambda virus is able to remain dormant in E. coli bacteria because its repressor binds to the viral DNA, preventing the expression of the genes necessary for viral replication.

The repressor motif is used in gene regulation in many other organisms, but for years, prominent researchers had failed to isolate a repressor, Ptashne says.

"I went into science because I became alerted to the idea of there being a repressor and began collaborating and competing with [Leob University Professor] Wally Gilbert, who was at the time looking for the lac repressor," Ptashne says.

Years later, the ABC television network produced a movie detailing the friendly competition between Ptashne and Gilbert at the recommendation of James L. Watson, co-discoverer of the structure of DNA.

Ptashne recorded his work with lambda repressor in 'A Genetic Switch,' a monograph considered by many scientists to be one of the classics of molecular biology. The book is used by Harvard students taking Biological Sciences 10: "Introductory Molecular Biology," Biological Sciences 14: "Genetics," and Biological Sciences 1: "Introductory Genetics, Molecular, Cellular and Developmental Biology."

After characterizing the lambda repressor, Ptashne began applying the principles of gene regulation in lambda phage virus to higher organisms.

"In 1988 we made a few observations that enabled us to argue that the principles of gene regulation in higher organisms can be understood with certain modifications of what we know in lambda," Ptashne says. "Those principles of gene regulation in higher organisms were then explained in the second edition of 'A Genetic Switch."

Ptashne says he hopes an understanding of the basic mechanism of the repressor's activity can be applied to broader issues, such as determining the evolutionary basis of transcription-based gene regulation.

"[We are studying] how evolution uses a limited number of activators to turn on many different genes in many different programs." Ptashne says. "If you can understand this then you can understand how regulation evolved."

Ptashne is now investigating gene regulation in higher organisms from various angles.

"We are continuing on a variety of fronts using various eukaryotes [such as] yeasts and mammalian cells to understand these chemical principles," Ptashne.

"Our focus is different from that of many labs working on gene regulation." Ptashne says. "It's not so much discovering new examples of regulators but rather understanding what are the common chemical principles that regulate genes. The message from lambda is that you can't study the patterns of gene expression without studying the underlying mechanism."

Ptashne says that Nusslem Volhard's work on the development of front fly embryos shows that many of the complicated patterns of gene regulation during development can be understood in terms of the Lambda mechanism.

"By reiterating these transcriptions elements, you can evidently make a fly," Ptashne says.

A Young Start