News and Publications

"Binary" Enzyme Demonstrates Darwinian Evolution at its Simplest

TSRI Research Associate John S. Reader, D.Phil., and Professor Gerald F. Joyce, M.D., Ph.D., have succeeded in creating an enzyme based on a "binary" genetic code--one containing only two different subunits.

This research demonstrates that Darwinian evolution can occur in a genetic system with only two bases, and it also supports a theory in the field that an early form of life on earth may have been restricted to two bases.

"Nobody will ever top this because binary systems are the most reduced form of information processing," says Joyce. "Two different subunits are the absolute minimum number you need [for Darwinian evolution]."

Reference: Nature, 420, 841-844 (2002).

Expanding the Genetic Code

Scientists at TSRI report the synthesis of a form of the bacterium Escherichia coliwith a genetic code that uses 21 basic amino acid building blocks to synthesize proteins--instead of the 20 found in nature.

This is the first time that anyone has created a completely autonomous organism that uses 21 amino acids and has the metabolic machinery to build those amino acids.

"We now have the opportunity to ask whether a 21-amino acid form of life has an evolutionary advantage over life with 20 amino acids," says the report's lead author Professor Peter G. Schultz, Ph.D., who is Scripps Family Chair.

"We have effectively removed a billion-year constraint on our ability to manipulate the structure and function of proteins," he says.

In addition to demonstrating that life is possible with additional amino acids, the work enables scientists to chemically manipulate the proteins that an organism produces within the organism itself. This gives scientists a powerful tool for research, from determining molecular structures to creating molecular medicines.

Reference: JACS, 125(4), 935-939 (2003).

TSRI Scientists Discover a New Approach for Treating "Misfolding Diseases"

Professor Jeffery W. Kelly, Ph.D., and his colleagues in the Department of Chemistry and The Skaggs Institute for Chemical Biology at TSRI have demonstrated a new approach for treating "amyloid" diseases--particularly transthyretin amyloid diseases, which are similar to Parkinson's and Alzheimer's.

These amyloid diseases are caused by proteins misfolding into a structure that leads them to cluster together, forming microscopic fibril plaques made up of hundreds of these misfolded proteins. The plaques deposit in internal organs and interfere with normal function, sometimes lethally.

In a recent study, Kelly, who is Lita Annenberg Hazen Professor of Chemistry in The Skaggs Institute for Chemical Biology and TSRI's vice president for academic affairs, and his colleagues demonstrate the efficacy of using small molecules to stabilize the normal "fold" of transthyretin. Using this method, researchers were able to inhibit the formation of fibrils.

"I'm very excited about pursuing these potential therapeutic opportunities," says Kelly.

Reference: Science, 299, 713-716 (2003).

TSRI Scientists Lerner and Schultz Win Top German Prize

TSRI President Richard A. Lerner, M.D., and Professor Peter G. Schultz, Ph.D., both members of TSRI's Skaggs Institute for Chemical Biology, were recently awarded the Paul Ehrlich and Ludwig Darmstaedter Prize, one of the most renowned prizes in the Federal Republic of Germany in the field of medicine.

Lerner, who is Lita Annenberg Hazen Professor of Immunochemistry and Cecil H. and Ida M. Green Chair in Chemistry, and Schultz, who is Scripps Family Chair, were selected for their achievements in connection with the development of catalytic antibodies. These molecules combine the enormous diversity of antibodies with the catalytic properties of enzymes.

$24-Million Grant Funds Encyclopedia of the Innate Immune System

The National Institute of Allergy and Infectious Diseases has awarded a multi-year, $24-million grant to a group of researchers at TSRI, the Institute for Systems Biology, and The Rockefeller University.

The group's task is to create an "encyclopedia" of innate immunity--a comprehensive and detailed picture of this ancient, essential first line of defense against bacterial and fungal diseases that is mustered by humans, fruit flies, and all creatures in between.

The funds will go towards discovering new ways to study the immune system in living tissue in real time and to provide materials and information to the scientific community at large. Knowledge generated could help scientists develop treatments for septic shock, certain autoimmune disorders, and diseases caused by potential agents of bioterrorism.