The Catholic University of America

Aug. 24, 2009

Biology Professor Receives $2.4 Million to Uncover Mysteries of a Virus


Venigalla Rao

Medical breakthroughs often come as a result of more humble basic research - for example, doing the painstaking work to understand the structure and processes of microorganisms … even microorganisms that have nothing to do with human health.

To pursue such understanding of an innocuous virus called bacteriophage T4, CUA biology Professor Venigalla Rao has in the past month received a $1 million National Science Foundation grant and two National Institutes of Health grants worth a combined $1.4 million.

Rao's 29 years of research into this virus - called a bacteriophage because it infects bacteria - led earlier this year to his receiving a $2.5 million National Institutes of Health grant to develop a vaccine against both anthrax and pneumonic plague - two deadly diseases that the Centers for Disease Control and Prevention describes as Category A threats for use in bioterrorism attacks against this country.

Getting to know the structure of bacteriophage T4 helped Rao to see how the microorganism could be used as a vehicle to carry innovative new vaccines into a human body.

With the aid of the three new NSF and NIH grants, the professor will be doing more research into the incredibly small but incredibly complex world of the bacteriophage and its reproductive cycle. This research, too, holds promise for future medical breakthroughs, Rao says.

Thanks to the new $1 million five-year National Science Foundation grant, Rao and his team of CUA researchers will study one of the strongest biological motors known: the bacteriophage's "packaging machine" that allows it to reproduce within a host bacterium by rapidly pulling a long strand of DNA into a tiny shell the bacteriophage manufactures.

"This motor would be twice as powerful as the typical automobile engine if it were scaled to the size of a car engine," says Rao. The actual size of the motor (which is shaped like a flying saucer) is approximately 17 nanometers wide and 10 nanometers high. (One nanometer is equal to one millionth of a millimeter or one billionth of a meter.)

The strand of DNA is enormously longer than the shell that the virus places it into. In packing the shell, the virus folds the DNA strand about 700 times. A single knot during this process could "kill" transmission of the bacteriophage's genetic material, says Rao.

"The similarities between the bacteriophage T4 and human viruses such as herpes viruses make T4 a particularly attractive model to elucidate mechanisms shared by different viruses, as well as to discover novel anti-viral interventions," says Rao.

"Another attractive possibility is engineering the DNA-packaging nanomotor to make it deliver therapeutic molecules into targeted cells to treat infectious disease or cancer."

Exploring the latter possibility is the raison d'être of one of Rao's new National Institutes of Health grants, worth about $400,000 over two years. The professor will seek to re-engineer the bacteriophage motor to transport a therapeutic molecule such as RNA or a peptide into cells of the human body.

For the other NIH grant, worth about $1 million over five years, Rao's lab will be working in cooperation with a Purdue University structural biologist, Professor Michael Rossmann. The purpose of this research is to gain greater understanding of the bacteriophage T4. Rao's work will involve studying the atomic structures of the motor, tail, DNA-receiving shell and other components.

"Dr. Rao has had an incredibly productive research career, and is widely recognized as one of the predominant authorities in the overall areas of molecular biology, immunology and associated applications such as vaccine development," says Dr. Carl R. Alving, chief of adjuvant and antigen research for HIV vaccines at the Walter Reed Army Institute of Research, located in Rockville, Md.

MEDIA: For more information, contact Katie Lee or Mary McCarthy in Catholic University's Office of Public Affairs at 202-319-5600.