Featured Research

from universities, journals, and other organizations

Researchers Improve Design Of Genetic On-off Switches

Date:
May 9, 2005
Source:
University of Illinois at Urbana-Champaign
Summary:
Researchers at the University of Illinois at Urbana-Champaign have set a new standard in the design and engineering of nuclear hormone receptor-based genetic on-off switches, without causing new problems or aggravating existing ones.

Huimin Zhao, left, a professor of chemical and biomedical engineering, and graduate student Zhilei Chen have changed the function of a protein using a co-evolution approach.
Credit: Photo by Kwame Ross

CHAMPAIGN, Ill. -- Researchers at the University of Illinois at Urbana-Champaign have set a new standard in the design and engineering of nuclear hormone receptor-based genetic on-off switches, without causing new problems or aggravating existing ones.

Related Articles


The new technique, published online ahead of regular publication by the Proceedings of the National Academy of Sciences, combines the advantages of directed evolution and computationally driven rational design, said Huimin Zhao, a professor in the department of chemical and biomolecular engineering and member of the Institute for Genomic Biology at Illinois.

Zhao's team, using yeast and mammalian cells, altered the specificity of human estrogen receptor alpha by 100 million times so it would bind preferentially to a non-toxic synthetic molecule (4,4'-dihydroxybenzil) over the natural estrogen 17-beta-estradiol.

Such selectivity moves researchers closer to designing synthetic molecules that will attach to only targeted receptors to activate or deactivate desired gene expression in living systems, which could lead to advances in such applications as gene therapy, metabolic engineering, functional genomics, enzyme engineering and animal disease model studies.

Many previous attempts, using a variety of molecular methods, have involved time-consuming approaches that have resulted in unintended activity when non-targeted receptors have responded to the new molecules.

"I'm not saying that we have solved the problem, but we have shown that our approach can be very efficient and done successfully," said Zhao, also an affiliate in the chemistry and bioengineering departments and member of the Center for Biophysics and Computational Biology. "We were able to alter the ligand (molecule) selectively by 10 to the 8th in mammalian cells. No one has had this high level of success."

The Illinois approach, Zhao said, is more general, quicker to accomplish and more accurate than a scientifically hailed combinational approach published in PNAS last October by researchers at the Georgia Institute of Technology. In their paper, the Georgia scientists used random mutagenesis and chemical complementation to develop a yeast-based system that made a retinoid X receptor, a nuclear hormone receptor, recognize and bind to a synthetic molecule.

The protein-engineering approach used by Zhao's team used directed evolution, which mimics natural evolution in a test tube, to force rapid evolution of human estrogen receptor with new ligand specificity. This process is done mainly through stepwise, site-saturation mutagenesis and high throughput screening.

The sites of human estrogen receptor chosen for saturation mutagenesis were identified through rational design, which involves computational modeling and biochemical and genetic studies to predict the interactions between the receptor and the ligand and the myriad molecular interactions that take place to drive gene expression. The engineered genetic changes subsequently make the receptor highly sensitive to the synthetic molecule that is introduced.

"We envision that the described technology could provide a powerful, broadly applicable tool for engineering receptors/enzymes with improved or novel ligand/substrate specificity," Zhao said.

###

Co-authors with Zhao were Karuppiah Chockalingam and Zhilei Chen, both doctoral students in chemical and biomolecular engineering, and John A. Katzenellenbogen, a Swanlund Endowed Chair in chemistry and affiliate of the Beckman Institute of Advanced Science and Technology at Illinois.

A patent is being sought for the protein-engineering technology and gene switch.

A National Science Foundation Faculty Early Career Development Award grant to Zhao funded the research.


Story Source:

The above story is based on materials provided by University of Illinois at Urbana-Champaign. Note: Materials may be edited for content and length.


Cite This Page:

University of Illinois at Urbana-Champaign. "Researchers Improve Design Of Genetic On-off Switches." ScienceDaily. ScienceDaily, 9 May 2005. <www.sciencedaily.com/releases/2005/05/050508152740.htm>.
University of Illinois at Urbana-Champaign. (2005, May 9). Researchers Improve Design Of Genetic On-off Switches. ScienceDaily. Retrieved March 29, 2015 from www.sciencedaily.com/releases/2005/05/050508152740.htm
University of Illinois at Urbana-Champaign. "Researchers Improve Design Of Genetic On-off Switches." ScienceDaily. www.sciencedaily.com/releases/2005/05/050508152740.htm (accessed March 29, 2015).

Share This


More From ScienceDaily



More Plants & Animals News

Sunday, March 29, 2015

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Raw: Lioness Has Rare Five-Cub Litter

Raw: Lioness Has Rare Five-Cub Litter

AP (Mar. 27, 2015) — A lioness in Pakistan has given birth to five cubs, twice the usual size of a litter. Queen gave birth to two other cubs just nine months ago. (March 27) Video provided by AP
Powered by NewsLook.com
Jockey Motion Tracking Reveals Racing Prowess

Jockey Motion Tracking Reveals Racing Prowess

Reuters - Innovations Video Online (Mar. 26, 2015) — Using motion tracking technology, researchers from the Royal Veterinary College (RVC) are trying to establish an optimum horse riding style to train junior jockeys, as well as enhance safety, health and well-being of both racehorses and jockeys. Matthew Stock reports. Video provided by Reuters
Powered by NewsLook.com
Bear Cubs Tumble for the Media

Bear Cubs Tumble for the Media

Reuters - Light News Video Online (Mar. 26, 2015) — Two Andean bear cubs are unveiled at the U.S. National Zoo in Washington, D.C. Alicia Powell reports. Video provided by Reuters
Powered by NewsLook.com
Botswana Talks to End Illegal Wildlife Trade

Botswana Talks to End Illegal Wildlife Trade

AFP (Mar. 25, 2015) — Experts are gathering in Botswana to try to end the illegal wildlife trade that is decimating populations of elephants, rhinos and other threatened species. Duration: 01:05 Video provided by AFP
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
 
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:  

Breaking News:

Strange & Offbeat Stories

 

Plants & Animals

Earth & Climate

Fossils & Ruins

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:  

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile iPhone Android Web
Follow Facebook Twitter Google+
Subscribe RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins