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.

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 September 2, 2014 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 September 2, 2014).

Share This




More Plants & Animals News

Tuesday, September 2, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

U.N. Says Ebola Travel Restrictions Will Cause Food Shortage

U.N. Says Ebola Travel Restrictions Will Cause Food Shortage

Newsy (Sep. 2, 2014) — The U.N. says the problem is two-fold — quarantine zones and travel restrictions are limiting the movement of both people and food. Video provided by Newsy
Powered by NewsLook.com
Sharks Off the Menu and on the Tourist Trail in Palau

Sharks Off the Menu and on the Tourist Trail in Palau

AFP (Sep. 2, 2014) — Tourists in Palau clamour to dive with sharks thanks to a pioneering conservation initiative -- as the island nation plans to completely ban commercial fishing in its vast ocean territory. 01:15 Video provided by AFP
Powered by NewsLook.com
We've Got Mites Living In Our Faces And So Do You

We've Got Mites Living In Our Faces And So Do You

Newsy (Aug. 30, 2014) — A new study suggests 100 percent of adult humans (those over 18 years of age) have Demodex mites living in their faces. Video provided by Newsy
Powered by NewsLook.com
Coffee Then Napping: The (New) Key To Alertness

Coffee Then Napping: The (New) Key To Alertness

Newsy (Aug. 30, 2014) — Researchers say having a cup of coffee then taking a nap is more effective than a nap or coffee alone. Video provided by Newsy
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:
from the past week

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