Philip Serwer, PhD



focus on understanding the dynamics of two intertwined processes: (1) the cycle and energy transduction of bacteriophage DNA packaging motors and (2) the past and present evolution of bacteriophages. Both topics are believed to be fundamental to understanding eukaryotes, as well. Study of bacteriophages, of course, has been fundamental to the development of all past molecular biology. We are extending that tradition.

We use two strategies for the analysis of DNA packaging motors: (1) fractionation of an interrupted motor by the amount of DNA packaged and then determination of physical/chemical changes of the motor as more DNA is packaged (traditional ensemble averaging strategy) and (2) observation of a cycling single motor in real time and use of fluorescent probes to observe various aspects of the motor dynamics (single-molecule strategy). These two strategies are basically equivalent and complementary, but differ in the level of analysis possible with the various aspects of DNA packaging motor. For, example, we and our collaborators at Purdue University have, for the first time, used the ensemble averaging strategy to find that the initially packaged DNA is randomly arranged in a bacteriophage capsid and that DNA order begins at the inner surface of the capsid’s outer shell and proceeds inward. Our ensemble averaging strategy appears to be close to yielding even more incisive results, based, in part, on our previous development of non-denaturing gel electrophoresis. Our single-molecule strategy has demonstrated that DNA packaging is co-operative for a bacteriophage that cleaves and packages a genome from a multigenomic concatemer. We both have been and are working on more incisive implementation of the single-molecule strategy, as are other groups. We focus on observing the biochemistry for single, untethered molecules diffusing in solution.

We study both past and present (in laboratory) evolution. To study past evolution, we isolate new bacteriophages and then work with experts in DNA sequencing/annotation to characterize genes and arrange them in families related through common ancestors. Our primary collaborator is the laboratory of Stephen C. Hardies of our department. This collaborative effort has (1) traced the evolution of DNA packaging ATPases and yielded some striking ideas about DNA binding during packaging, (2) produced the longest bacteriophage DNA sequence in GenBank and (3) discovered a bacteriophage that is in a new genomic class and that has characteristics that appear to be of extremely high importance for the future of all virology. For the study of present evolution, we have achieved the first bacteriophage/host co-evolution for a sequenced bacteriophage. We think that improvements in the following will be spin-offs of this work: display vectors, vaccines and infectious disease management (improved phage therapy, for example).