Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Researchers improve design of genetic on-off switches

08.04.2005


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.

Jim Barlow | EurekAlert!
Further information:
http://www.uiuc.edu

More articles from Life Sciences:

nachricht New application for acoustics helps estimate marine life populations
16.01.2018 | University of California - San Diego

nachricht Unexpected environmental source of methane discovered
16.01.2018 | University of Washington Health Sciences/UW Medicine

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Scientists decipher key principle behind reaction of metalloenzymes

So-called pre-distorted states accelerate photochemical reactions too

What enables electrons to be transferred swiftly, for example during photosynthesis? An interdisciplinary team of researchers has worked out the details of how...

Im Focus: The first precise measurement of a single molecule's effective charge

For the first time, scientists have precisely measured the effective electrical charge of a single molecule in solution. This fundamental insight of an SNSF Professor could also pave the way for future medical diagnostics.

Electrical charge is one of the key properties that allows molecules to interact. Life itself depends on this phenomenon: many biological processes involve...

Im Focus: Paradigm shift in Paris: Encouraging an holistic view of laser machining

At the JEC World Composite Show in Paris in March 2018, the Fraunhofer Institute for Laser Technology ILT will be focusing on the latest trends and innovations in laser machining of composites. Among other things, researchers at the booth shared with the Aachen Center for Integrative Lightweight Production (AZL) will demonstrate how lasers can be used for joining, structuring, cutting and drilling composite materials.

No other industry has attracted as much public attention to composite materials as the automotive industry, which along with the aerospace industry is a driver...

Im Focus: Room-temperature multiferroic thin films and their properties

Scientists at Tokyo Institute of Technology (Tokyo Tech) and Tohoku University have developed high-quality GFO epitaxial films and systematically investigated their ferroelectric and ferromagnetic properties. They also demonstrated the room-temperature magnetocapacitance effects of these GFO thin films.

Multiferroic materials show magnetically driven ferroelectricity. They are attracting increasing attention because of their fascinating properties such as...

Im Focus: A thermometer for the oceans

Measurement of noble gases in Antarctic ice cores

The oceans are the largest global heat reservoir. As a result of man-made global warming, the temperature in the global climate system increases; around 90% of...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

10th International Symposium: “Advanced Battery Power – Kraftwerk Batterie” Münster, 10-11 April 2018

08.01.2018 | Event News

See, understand and experience the work of the future

11.12.2017 | Event News

Innovative strategies to tackle parasitic worms

08.12.2017 | Event News

 
Latest News

Novel 3-D printing technique yields high-performance composites

16.01.2018 | Materials Sciences

New application for acoustics helps estimate marine life populations

16.01.2018 | Life Sciences

Fast-tracking T cell therapies with immune-mimicking biomaterials

16.01.2018 | Health and Medicine

VideoLinks
B2B-VideoLinks
More VideoLinks >>>