Columns::August 20, 2001
UGA receives more than $54 million in new gifts, pledges
Consultants: Pay and classification system should be revamped
Collaborative effort begins
Montana administrator chosen to lead UGA’s international programs
Campus Closeup
New assistant dean named for Tifton ag and environmental sciences
Kudos
Great universities require great faculty leadership
Newsworthy
Campus News
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| Julie Burke (left), a graduate student in the lab of genetics professor Janet Westpheling (right), helped develop the new technique for manipulating Streptomyces bacteria. Photo by Peter Frey |
Moving experience
UGA genetics research team develops new system to transfer DNA from one bacterium to another
By Phil Williams
phil@franklin.uga.edu
A research team at UGA, under the leadership of Janet Westpheling of the genetics department, has successfully transferred DNA into genetically uncharacterized species of the important bacterium Streptomyces.
The system is based on the use of phages (bacterial viruses) that infect these bacteria to transfer DNA from the host they are grown on to a recipient they later infect. This procedure has several important advantages over current technology and will make it far easier--in some cases, it will make it possible for the first time--for pharmaceutical companies to develop
Streptomyces-based antibiotics and anti-cancer drugs.
Results of the study were published earlier this year in the Proceedings of the National Academy of Sciences.
“This will allow, for the first time, for example, the study and manipulation of the bleomycin biosynthetic pathway in the producing organism,” says Westpheling. “Bleomycin is an important anti-cancer chemotherapeutic drug that has so far been completely refractory to genetic manipulation. We anticipate that the ability to get DNA into this strain of Streptomyces will lead to the production of novel bleomycins.”
Westpheling, who reported on the discovery at an international meeting in Singapore earlier this year, gives major credit for the discovery to two students in her laboratory who were convinced that the transfer--considered impossible by many scientists--could be successfully accomplished.
Julie Burke, a graduate student, and David Schneider, an undergraduate, originated the idea for the transfer system. A patent for the use of this technology in antibiotic drug discovery was issued to the University of Georgia Research Foundation this past November.
The idea of using transduction--moving DNA from one organism to another using viruses called phages as carriers--is not new. Numerous problems had made transduction impractical if not impossible in Streptomyces, however. Researchers have desired such a system because it would allow the design of stronger or different drugs to fight infection or cancer.
There are, in fact, hundreds of species of Streptomyces, more than two dozen of which are currently being used to produce drugs to improve human and animal health. However, since Streptomyces could not be manipulated using genetic techniques, the drugs must be created directly from soil-borne organisms, which can be time-consuming and expensive. Worse, resistance to commonly used antibiotics is growing more pronounced every year; new strains of infections are killing patients who might have survived a few years ago. Soil-borne Streptomyces aren’t evolving quickly enough to keep up with the pathogens.
“The need for new and improved antibiotics is becoming a major issue for human health care,” Westpheling says. “There are many ‘orphan’ drugs out there waiting to be developed, if only the organisms that produce them could be manipulated. In addition, the ability to shuffle the genetic pathways for existing drugs may lead to the production of truly new types of compounds for which there is no resistance.”
In Streptomyces, phage-mediated DNA transfer was ineffective because the phages are extremely virulent, killing the cells that received the DNA. Westpheling and her team found a way to remove the phages’ lethal impact--using a technique called superinfection killing--allowing them to serve as DNA carriers without killing the target cells.
The researchers used a strain called Streptomyces coelicolor, genetically the best-characterized actinomycete. Actinomycetes are an extremely diverse group of filamentous prokaryotic organisms that includes most of the major natural-product antibiotics. They are unique among bacteria in that they grow as a branching hyphae, similar to fungi, as they gather nutrients from the soil. S. coelicolor has attracted considerable interest as a model for studying strains of Streptomyces that make important therapeutics.
The new genetic “postal system” developed by the research team will allow researchers to create novel chemical backbones to change or improve the function of Streptomyces in fighting infection or cancer.
In addition to its practical importance in drug development, transduction in Streptomyces will have a significant impact on the study of the biology of these organisms. Generalized transduction is a major tool that scientists use to map and manipulate such highly developed model systems as E. coli. |
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