Wednesday, November 21, 2012

USA Research Seeks To Better Understand Rickettsia prowazekii

Research led by Dr. David O. Wood (left) seeks to find a vaccine for epidemic typhus.  Dr. Wood, who came to USA in 1979,  is pictured with post-doctoral fellow Dr. Aimee Tucker.

Dr. David Wood, professor and chair of microbiology at the University of South Alabama College of Medicine, was awarded a renewal grant in its 27th year by the National Institutes of Health (NIH) for the research surrounding a vaccine for epidemic typhus, one of the most deadly diseases affecting humans. He credits much of his success to his mentor Dr. Herbert Winkler, who introduced him to the research surrounding the bacteria responsible for epidemic typhus, Rickettsia prowazekii, when he arrived at USA in 1979.

“My early discussions with Dr. Winkler revealed that very little in the way of genetic analysis had been done in the rickettsial field, and as a true mentor, he encouraged me to pursue my interests in the area,” Dr. Wood said. “I became very excited about understanding how the rickettsiae exploit host cells and how I could address the challenges that the intracellular lifestyle places on genetic analysis.”

Dr. Wood said that his interaction with Dr. Winkler inspired him to submit his first rickettsial NIH grant proposal, but early critiques were very unfavorable. Although he was very enthusiastic about the project, NIH decided not to fund him the initial year.

“As a young tenure-track assistant professor, I did not want to go to my mentors and let them know that they hired someone who received such rejections,” he said of the NIH decision. “I was extremely fortunate to have Dr. Winkler as a mentor and Dr. Joseph Coggin as a chair who continued to strongly support and encourage me despite the initial setback.”

According to Dr. Wood, this setback only fueled his motivation and led to his collaboration with Dr. Winkler on cloning and expressing the first rickettsial gene. This led to the submission of a second proposal that was funded, and has continued to be consecutively funded for nearly three decades. Dr. Wood also is only one of five at USA to be awarded a MERIT (Method to Extend Research in Time) award, which is among the most selective grants awarded by NIH.

Dr. Wood explained that rickettsiae are associated with vectors such as lice or ticks, and they can transmit the rickettsiae to humans. He is very interested in the unusual biology of the rickettsiae because they only grow in the cytosol, or the liquid component is inside host cells. Instead of being enclosed within a vacuole, which normally isolate materials that might be harmful to the cell, the organisms can escape into the cytosol where they grow until the number of rickettsiae becomes so great that the cell bursts, releasing hundreds of infectious bacteria. The primary focus of his team’s work revolves around understanding how the agent is able to behave this way and identifying new targets for antimicrobial agents or developing vaccines that could potentially help people become immune to epidemic typhus.

 “Our ultimate goal is to gain a better understanding of this novel infectious disease agent and develop a good vaccine,” he said. “Coming up with a vaccine for epidemic typhus could save many lives,” he added.

The research initiated by Dr. Herbert Winkler more than 30 years ago has helped to establish a Select Agent Program centered on Rickettsia. This motivated others, like Dr. Wood and his colleagues, to obtain NIH funds for the construction of a new research lab. The 25,800-square-foot Laboratory of Infectious Diseases building (LID) will be located in the USA Technology and Research Park on the north side of USA’s campus. It will replace the current Biosafety Level 3 (BSL-3) laboratory building, and will more than double the current Biosafety Level 3 research capability at USA.