Wednesday, July 26, 2006

Writer:  Carole VanSickle, 706/583-0599, rcomm@ovpr.uga.edu
Contact:  Gene Gama, 706/583-8088, gjg@ovpr.uga.edu

University of Georgia molecular biologists develop high-speed method for protein production

Athens, Ga. – UGA researchers have developed a new method of protein expression that will enable scientists to at least quadruple their rate of protein production in experiments.

“Proteins are important in many aspects of scientific research,” said Peter Horanyi, a former UGA doctoral student who is now an associate researcher at the University of Virginia. “The unique thing about this new procedure is that it could have a major impact in many areas of biology.”

Horanyi and team members Francis E. Jenney Jr., James Griffith and Bi-Cheng Wang at UGA’s South East Collaboratory for Structural Genomics said that this research will benefit the study of genomics – the high speed or high-throughput study of biological molecules and their structure and function – as well as work in RNA interference in the worm C. elegans, a model used by researchers to study subjects as diverse as Alzheimer’s disease, diabetes and aging and development of new therapies against infectious diseases such as influenza.

Proteins play a vital role in research because they are frequently the mechanism by which genes exert their function.

“In our field, we want to investigate the structure of every protein,” Horanyi said. “Protein structure and function are related, so if we can decipher the atomic structure of a protein then often we can understand its most intricate function.”

However, in order to view the structure of a protein, in most cases it is necessary to crystallize that protein. This can be a difficult and time-consuming task.

“It used to take days to design and create a protein that might or might not be ‘solvable’ once you were done,” said Wang, UGA’s Ramsey-Eminent Scholar in Structural Biology, referring to the ability to view a protein’s structure. “This technology, however, will let us express four alternate versions of a protein at once – thereby quadrupling our chances of success with each attempt.”

Traditional techniques require four to eight weeks of work to clone 96 genes into three vectors. UGA’s technology allows for the same work to be done in less than 4 days.

Wang added that the team also has succeeded in introducing a facet that will enable scientists to use E. coli – a common bacteria often used to ‘manufacture’ proteins for experiments – to make proteins not usually manufactured by that particular organism. This will make protein production quicker and easier for research scientists in many areas of scholarship.

The team has been working with Edward Kipreos, a UGA geneticist, to test their new method of inactivating multiple genes simultaneously.

“Because C. elegans is a well-developed model system, we can analyze multiple mutant phenotypes at the same time to confirm that different genes are being targeted,” Kipreos said. “For example, if we produce a worm that is short and fat – a mutation called ‘dumpy’ – and has a bobbed tail, then we know that we inactivated two genes at once.” The team is interested in seeing just how many genes can be inactivated simultaneously.

The technology, the subject of patent applications by UGA Research Foundation, also allows for the production of protein complexes – several proteins bundled together – circumventing serious solubility problems commonly associated with biofermentation. In the past, it has been difficult and time consuming to make enough protein complexes to ensure that some of them would be amenable to structural imaging.

“Protein production is at the core of biotechnology and pharmaceutical industries,” said Gennaro Gama, a UGARF technology commercialization officer. “The potential impact of this technology on the biotechnology and pharmaceutical industries is tremendous.”

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