ATP-driven biological motors are essential to the complex biochemistry of both eukaryotes and prokaryotes. The Pl's research focuses on understanding bacteriophage DNA packaging motors because these motors provide advantages during biochemical/biophysical analysis. A bacteriophage DNA packaging motor is a multimolecular ring attached to an icosahedral protein shell (capsid). A central hole in the ring is a channel through which a double-stranded DNA molecule is motor-driven into the capsid during DNA packaging. Central questions for all biological motors are the following: Is the motor's cycling rate feedback regulated? What is the source of the directional bias of the motor, given the small size and, therefore, high thermal motion of components? What are the details of the motor's cycle? The PI has proposed a detailed hypothesis that has potential answers to these questions. This hypothesis states that a DNA packaging motor has a cycling rate that is feedback regulated. Furthermore, this hypothesis states that the motor is an osmotic pressure gradient-assisted device that has the capacity to be a thermal ratchet.
The Specific Aims are the following: (1) The Pl's hypothesis will be tested directly in several aspects. Tests will be performed for whether the motor's cycle is feedback regulated. Tests will also be performed for osmotic pressure-derived DNA packaging force. (2) The various states of a cycle of the DNA packaging motor will be identified and characterized. Recently discovered states of variable capsid size and permeability will be investigated. Analysis will be performed of the temporal relationship among intermediate states during a cycle of a DNA packaging motor. Some analyses will be performed by single-particle fluorescence microscopy. The DNA packaging motors to be studied are those of bacteriophages f29, T3 and T7. The data to be obtained will answer central questions about biological motors, whether or not the Pl's hypothesis is correct. Analysis of bacteriophage DNA packaging motors is expected to provide a basis for understanding the role of motors in disease, especially disease caused by a virus that has a DNA packaging motor. ? ?
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