Yale researchers use genetic code engineer living protein

Yale researchers use genetic code to engineer a living protein

4:43 AM, 26th August 2011
Yale researchers use genetic code to engineer a living protein

 

NEW HAVEN, US: Yale University researchers have successfully re-engineered the protein-making machinery in bacteria, a technical tour de force that promises to revolutionize the study and treatment of a variety of diseases.

“Essentially, we have expanded the genetic code of E coli, which allows us synthesize special forms of proteins that can mimic natural or disease states,” said Jesse Rinehart of the Department of Cellular and Molecular Physiology and co-corresponding author of the research published in the August 26 issue of the journal Science.

Scientists have been working hard to understand the nature of genetic code. Research and recent advances in synthetic biology has given researchers tools to modify the natural genetic code.

“What we have done is taken synthetic biology and turned it around to give us real biology that has been synthesized,” explained Rinehart.

The Yale team - under the direction of Dieter Soll, Sterling Professor of Molecular Biophysics and Biochemistry, Professor of chemistry and corresponding author of the paper - developed a new way to influence the behaviour of proteins, which carry out almost all of life’s functions. Instead of creating something new in nature, the researchers essentially induced phosphorylation, a fundamental process that occurs in all forms of life and can dramatically change a protein’s function. The rules for protein phosphorylation are not directly coded in the DNA but instead occur after the protein is made. The Yale researchers fundamentally rewrote these rules by expanding the E coli genetic code to include phosphoserine and for the first time directed protein phosphorylation via DNA.

This new technology now enables the production of human proteins with their naturally occurring phosphorylation sites, a state crucial to understanding disease processes. “What we are doing is playing with biological switches - turning proteins on or off, which will give us a completely new way to study disease states and hopefully guide the discovery of new drugs,” said Rinehart.

Soll and Rinehart are attempting to create proteins in states known to be linked to cancer, type 2 diabetes and hypertension.

“Dr Soll and his colleagues have provided researchers with a powerful new tool to use in uncovering how cells regulate a broad range of processes, including cell division, differentiation and metabolism,” said Michael Bender, who oversees protein synthesis grants at the National Institute of General Medical Sciences of the National Institutes of Health.

Other authors from Yale are lead authors Hee-Sung Park and Michael J Hohn, Takuya Umehara and L-Tao Guo. They collaborated with Edith M Osborne, Jack Benner, and Christopher J Noren from New England Biolabs.

The work was funded by grants from the National Science Foundation and the National Institutes of Health via the National Institute of General Medical Sciences and the National Institute of Diabetes and Digestive and Kidney Diseases.

© Yale University News

 

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